Oocyte morphology predicts outcome of intracytoplasmic sperm injection

To examine the influence of cytoplasmic morphology on the success rate of intracytoplasmic sperm injection (ICSI), the morphology of 837 metaphase II oocytes was assessed after cumulus stripping. The main abnormalities detected were excessive granularity, cytoplasmic inclusions such as vacuoles, smooth endoplasmic reticulum clustering and refractile bodies. Microinjection was performed in 538 oocytes with normal cytoplasm, 142 out of 161 with excessive granularity and 112 out of 138 with cytoplasmic inclusions. Very poor oocytes were not injected. No difference was found in fertilization rate. The embryos achieved cleaved normally and a similar number of good quality embryos among the three groups was noted. The outcome of transfer of embryos derived solely from normal oocytes (group A: 72 patients, 183 embryos) was compared with those from oocytes with cytoplasmic abnormalities (group B: 34 patients, 85 embryos). In group A, 17 clinical pregnancies (24% per patient, implantation rate 10%) were established. In group B, only one clinical pregnancy (3% per patient, implantation rate 1%) was established, from the transfer of embryos derived from oocytes with homogeneous granularity of the cytoplasm. No pregnancy resulted following the transfer of embryos from eggs with cytoplasmic inclusions. The difference was statistically significant. The outcome of ICSI is dependent on the quality of the oocytes retrieved. Normal fertilization and early embryo development were achieved in oocytes with abnormal cytoplasm morphology, but the resulting embryos failed to demonstrate the same implantation potential as those derived from oocytes with normal cytoplasm.      

Histologic grading of breast cancer: linkage of patient outcome with level of pathologist agreement.

In the histologic grading of invasive breast cancer with the Nottingham modification of the Scarff-Bloom-Richardson grading scheme (NSBR), it has been found that when pathologists disagree, they tend not to disagree by much. However, if tumor grade is to be used as an important parameter in making treatment decisions, then even this generally small degree of pathologist variability in assessing grade needs to be correlated with patient outcome. Findings from the Nottingham/Tenovus Primary Breast Cancer Study were used for patient outcome data. Kaplan-Meier survival curves were constructed for NSBR scores grouped according to the level at which pathologists tend to agree in assessing grade, from a reproducibility perspective. For example, if a given tumor were assessed by several pathologists as having either an NSBR score of 5 or 6, then what is the correct score--the intermediate-grade Score 6 assessments or the low-grade Score 5 assessments? By "regrouping" the Nottingham outcome data such that data from patients with Score 5 tumors are grouped with patients having Score 6 tumors (a 5-6 group), then the level in which the pathologists agreed with each other (that the tumor was either score 5 or 6) is better matched with patient outcome. In response to the above example, it was not surprising to find that patients with Score 5-6 tumors had a probability of survival between the established low and intermediate NSBR final combined grades. However, it is the discussion of this approach that highlights that optimal use of grading requires awareness of the level of pathologist agreement and understanding the value of pathologists' reaching consensus in assessments. Also, knowledge of possible clinical decision thresholds can help in providing relevant interpretations of grading results.     

Local shielding of high dose rate brachytherapy in an operating theatre

A high-dose rate brachytherapy facility was installed into an established operating theatre by using local shielding in the form of mobile lead screens and by taking advantage of the ease with which staff movements can be controlled in an operating suite. This facility was inexpensive to develop, and has proved clinically efficient and entirely adequate from a radiation safety standpoint.     

Mortality in Western Australian psychiatric patients

  Background: The aim was to examine mortality in psychiatric patients in Western Australia (WA), over a time period of considerable change in the delivery of mental health services. Methods: A population-based record linkage analysis was undertaken to quantify mortality among people with mental illness in WA. Mortality rates were calculated in users of mental health services and compared with rates in the whole population of WA. Trends in mortality were also examined using relative survival analysis, and proportional hazards regression. Results: The overall mortality rate ratio was 2.57 in males (95% CI: 2.51–2.64), and 2.18 in females (2.12–2.24). The highest cause-specific mortality rate ratio was for deaths due to suicide [RR: 7.37 in males (95% CI: 6.74–8.05) and 8.38 in females (95% CI: 7.11–9.89)], with mortality rate ratios being significantly greater than 1 for all other major causes of death. A relative survival analysis found that the excess mortality risk was concentrated in the first few years after first contact with mental health services. Proportional hazards regression analysis found a slight elevation of mortality rates over time. Conclusions: Mortality among psychiatric patients remains high and appears to be increasing. Highest excess mortality rate is associated with suicide, but mortality rates are significantly elevated for all major causes of death. Accepted: 10 April 2000     

Pathological Controversies in Breast Cancer: Classification of Ductal Carcinoma In Situ,Sentinel Lymph Nodes and Low Volume Metastatic Disease and Reporting of Neoadjuvant Chemotherapy Specimens

The pathological classification of breast cancer is constantly being updated to reflect the advances in our clinical and biological understanding of the disease. This overview examines new insights into the classification and molecular biology of ductal carcinoma in situ, the pathological handling of sentinel lymph node biopsies and the identification of low volume disease (micrometastases and isolated tumour cells) and the handling and reporting of specimens after neoadjuvant therapy. The molecular subtypes of invasive breast cancer are also represented in ductal carcinoma in situ. It is hoped that alongside traditional histological features, such as cytological grade and the presence of necrosis, this will lead to better classification systems with improved prediction of clinical behaviour, in particular the risk of progression to invasive cancer, and enable more targeted management. Sentinel lymph node biopsy is now the standard of care for early stage breast cancer in clinically node-negative patients. However, the handling and reporting of these specimens remains controversial, largely related to the uncertainties regarding the clinical significance of micrometastases and isolated tumour cells. The increasing use of neoadjuvant therapies has introduced challenges for the pathologist in the handling and interpretation of these specimens. Grading the tumour response, particularly the identification of a complete pathological response, is prognostically important. However, there is still marked variability in reporting these specimens in routine practice, and consensus guidelines for the histopathology reporting of breast cancers after neoadjuvant chemotherapy based on robust, validated evidence are presently lacking.     

Challenges in the management of pleomorphic lobular carcinoma in situ of the breast

BackgroundPleomorphic Lobular Carcinoma in Situ (PLCIS) is a pathological variant of Lobular Carcinoma in Situ (LCIS) with distinct features. Since first described over a decade ago there are only few papers published about this condition.MethodsMedline and Pubmed based literature overview was done with the aim of describing the different histopathological, radiological and clinical features of this pathological entity to highlight the different clinicopathological presentations and modalities of treatment described.ResultsPLCIS has different biological features when compared to LCIS. It is more likely to be associated with invasive disease and the immuno-histochemical profile shows it is less likely to be ER and PR positive with higher positivity of HER2, Ki-67and p53. It has been suggested that PLCIS should be treated more aggressively than LCIS and surgically excised in similar fashion to DCIS.ConclusionPLCIS is a more aggressive variant of LCIS that needs to be managed differently. Surgical excision with clear margins is advised. Further adjuvant treatments have been described in the literature with little evidence to support their use.