Impact of breast cancer grade discordance on prediction of outcome.

AIMS: Histological grade is an independent prognostic variable in breast cancer (BC). Previous concordance studies of BC grade have reported moderate levels of agreement; a typical finding in morphological assessment of biological variables. This study aimed to investigate the impact of discordance on the prognostic value of grade and to identify the best reporting approach in borderline cases. METHODS AND RESULTS: A large (n = 1675) well-characterised annotated cohort of BC, originally graded in routine practice using glass slides, was re-graded twice by an expert breast pathologist using virtual microscopy with a 3-month washout period. Outcome was assessed using breast cancer-specific and distant metastasis-free survival (median follow-up = 135 months). Fifty-eight per cent of the cases showed absolute agreement in the three separate grading sessions, whereas grades 1/2 and 2/3 discordance were observed in 21% and 21%, respectively. Absolute intra-observer agreement using virtual microscopy was observed in 77% of the cases, whereas 13% and 10% showed grades 1/2 and 2/3 discordance, respectively. Despite the concordance, outcome analysis revealed significant associations between tumour grade and patients' outcome in the three grading sessions. Grades 1/2 and 2/3 discordant cases showed intermediate survival between grades 1 and 2 tumours and grades 2 and 3 tumours, respectively. Grades 1/2 discordant cases showed a worse outcome when compared with grade 1 tumours (P = 0.008) but no statistical difference was identified when compared with grade 2 tumours. Similarly, grades 2/3 discordant cases showed a significant difference from grade 2 tumours (P < 0.001), but no statistical difference was identified when compared with grade 3 tumours. CONCLUSIONS: Breast cancer grade discordance is probably a reflection of biologically, and hence morphologically, borderline tumours. Cases with borderline features for grade are more likely to behave similarly to the higher-grade category. Repeating histological grade of borderline cases or double reporting may improve correlation with outcome.

The first year of behavioral development and maternal care of beluga (Delphinapterus leucas) calves in human care.

The current study provides additional information for the behavioral development and maternal care of belugas or white whales (Delphinapterus leucas) in the care of humans. The behaviors and mother-calf interactions of two female beluga calves were recorded from birth to 12 months as part of a longitudinal study of beluga behavioral development. As expected, the primary calf activity for both calves involved swimming with their mothers. The calves initiated the majority of the separations from and reunions with their mothers and exhibited early bouts of independence. Both mothers bonded with their calves and displayed similar maternal care behaviors but exhibited different behavioral patterns. Despite differences in social groupings, housing, and physical health, the two female belugas followed the behavioral development of beluga calves observed previously.

Management of twin pregnancy and perinatal concerns in a Beluga (Delphinapterus leucas).

A 22-yr-old multiparous beluga, Delphinapterus leucas, with consistently elevated serum progesterone concentrations post-artificial insemination was diagnosed with viable twins at 149 days postconception. Twins were of similar size at least until day 264, the last point when ultrasound measurements of both twins were made. However, ultrasound was used to determine the viability of both fetuses on days 365, 393, and 400. After 90% of normal gestation, or 434 days, steroids were administered to encourage fetal lung maturation. Seven days later a 40.9-kg live female calf was delivered headfirst. A second 22.7-kg stillborn calf was delivered in fluke-first presentation 8 hr later. Immediately after birth, the live calf was administered surfactant intratracheally. The next day, it was given beluga immunoglobulin intramuscularly, and started on oral antibiotics and provided nutritional support via an oral gastric tube. The calf started nursing voluntarily on day 3. Antibiotic and nutritional support was discontinued on day 10. Bimonthly weight and length measurements demonstrated that after an initial increased growth rate, the calf has grown within normal parameters after birth. This calf represents the first known successful surviving twin of any cetacean species and sets an important precedent for treatment modalities that may be available to assist the premature cetacean neonate.

West Nile virus infection in killer whale, Texas, USA, 2007.

In 2007, nonsuppurative encephalitis was identified in a killer whale at a Texas, USA, marine park. Panviral DNA microarray of brain tissue suggested West Nile virus (WNV); WNV was confirmed by reverse transcription PCR and sequencing. Immunohistochemistry demonstrated WNV antigen within neurons. WNV should be considered in cases of encephalitis in cetaceans.

Pure tone audiograms and possible aminoglycoside-induced hearing loss in belugas (Delphinapterus leucas).

A behavioral response paradigm was used to measure pure-tone hearing sensitivities in two belugas (Delphinapterus leucas). Tests were conducted over a 20-month period at the Point Defiance Zoo and Aquarium, in Tacoma, WA. Subjects were two males, aged 8-10 and 9-11 during the course of the study. Subjects were born in an oceanarium and had been housed together for all of their lives. Hearing thresholds were measured using a modified up/down staircase procedure and acoustic response paradigm where subjects were trained to produce audible responses to test tones and to remain quiet otherwise. Test frequencies ranged from approximately 2 to 130 kHz. Best sensitivities ranged from approximately 40 to 50 dB re 1 microPa at 50-80 kHz and 30-35 kHz for the two subjects. Although both subjects possessed traditional "U-shaped" mammalian audiograms, one subject exhibited significant high-frequency hearing loss above 37 kHz compared to previously published data for belugas. Hearing loss in this subject was estimated to approach 90 dB for frequencies above 50 kHz. Similar ages, ancestry, and environmental conditions between subjects, but a history of ototoxic drug administration in only one subject, suggest that the observed hearing loss was a result of the aminoglycoside antibiotic amikacin.