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D M Berney

Publications and source records attributed to D M Berney.

At least 19 recordsLinked to original sources

Markers of cell proliferation in a GH-producing adenoma of a patient treated with pegvisomant.

We report our findings on markers of cell proliferation (Ki-67 labelling index and topoisomerase-alpha expression) in a somatotroph pituitary tumour before and after exposure to pegvisomant, a GH receptor antagonist developed for the treatment of acromegaly. Specimens from two separate pituitary operations, separated by a period of 17 years that included 4 years of pegvisomant treatment, were stained for markers of cellular proliferation. Ki-67 labelling index and topoisomerase-alpha expression were both markedly greater (1-3% compared with 0-0.5% and 15-80% compared with 2-10% respectively) in the pegvisomant-exposed tumour compared with the earlier specimen. Clearly, caution must be exercised when interpreting findings from a single case, particularly one sufficiently refractory to conventional therapies to require treatment with pegvisomant. However, our data reinforce the requirement for careful radiological surveillance of the pituitary in the context of a drug that does not target the tumour responsible and where serum GH cannot serve as a marker of disease activity or tumour size.

Acromegaly↗

Prediction of progression in pTa and pT1 bladder carcinomas with p53, p16 and pRb.

Currently available prognostic tools appear unable to adequately predict recurrence and progression in non muscle-invasive bladder carcinomas. We aimed to assess the prognostic value of immunohistochemical evaluation of the cell cycle markers p53, p16 and pRb. Paraffin blocks were obtained from 78 cases of pTa and pT1 transitional cell carcinomas, for which long-term follow-up was available. Representative sections were stained using antibodies against p53, p16 and pRb. Altered marker expression was found in 45, 17 and 30% of cases, respectively. Concurrent alteration of two or three markers occurred in 19% of cases, and was significantly associated with grade and stage. In univariate survival analysis, the concurrent alteration of any two markers was significantly associated with progression. The greatest risk was produced by alteration of both p53 and p16, which increased the risk of progression by 14.45 times (95% confidence interval (CI) 3.10-67.35). After adjusting for grade and stage, this risk was 7.73 (CI 1.13-52.70). The markers did not generally predict tumour recurrence, except in the 25 pT1 tumours. In these, p16 alteration was associated with a univariate risk of 2.83 (CI 1.01-7.91), and concurrent p53 and p16 alteration with a risk of 9.29 (CI 1.24-69.50). Overall, we conclude that the immunohistochemical evaluation of p53 and p16 may have independent prognostic value for disease progression, and may help guide management decisions in these tumours.

Adult↗

The frequency of intratubular embryonal carcinoma: implications for the pathogenesis of germ cell tumours.

AIMS: To define the frequency and distribution of intratubular embryonal carcinoma (IEC) in an attempt to shed light on the pathogenesis of non-seminomatous germ cell tumours (NSGCTs). Intratubular germ cell neoplasia of unclassified type (IGCNU) is common in NSGCT; however, IEC is rarely described. METHODS AND RESULTS: Sixty-two germ cell tumours were reviewed. Immunochemistry for CD30, placental alkaline phosphatase (PLAP) and c-kit was performed. The distribution, immunohistochemistry and morphology of the intratubular neoplasia were noted. All cases showed widespread IGCNU with PLAP and c-kit staining. CD30 showed strong focal intratubular positivity in 20/31 NSGCTs, 1/29 seminomas and 1/4 mixed seminomas/NSGCTs. In 17 of these cases, the CD30+ tubules were not easily identified as IEC on routine stains. These tubules were scanty in number and c-kit was negative, though some showed patchy PLAP staining. The cells within these tubules differed morphologically from IGCNU. CONCLUSIONS: IEC defined by CD30 positivity is not always easily identified on haematoxylin and eosin staining. We suggest that IEC is a common intermediate step between IGCNU and NSGCTs. The patchy and focal distribution of IEC suggests it may evolve quickly to invasive disease.

Alkaline Phosphatase↗

Technical variations in prostatic immunohistochemistry: need for standardisation and stringent quality assurance in PSA and PSAP immunostaining.

AIMS: To assess variations in prostate specific antigen (PSA) and prostate specific acid phosphatase (PSAP) immunohistochemistry with particular reference to the antibody type (monoclonal or polyclonal) and the tissues used for optimising immunostaining conditions and as external positive controls. METHODS: A questionnaire was sent to all laboratories registered with the UK National External Quality Assurance Scheme for immunohistochemistry enquiring about the immunohistochemical methods routinely used for the diagnosis of prostate cancer. RESULTS: Responses were received from 220 (68%) laboratories. All UK respondents routinely performed PSA immunostaining but PSAP immunostaining was available in only 57% of these laboratories. Monoclonal anti-PSA, polyclonal anti-PSA, monoclonal anti-PSAP, and polyclonal anti-PSAP were used by 40%, 60%, 29%, and 27% of UK respondents, respectively. Benign prostate tissue was most commonly used to determine optimal antibody dilutions and as external quality control for PSA/PSAP, with only 6% and 3% of respondents, respectively, including high grade prostate cancer in the tissues used for these purposes. CONCLUSIONS: The wide variation in the methods used highlights the need for standardisation and more stringent quality assurance of the immunohistochemical staining techniques used for PSA and PSAP. The widespread use of benign prostate tissue to determine optimal antibody dilutions and as an external positive control for PSA and PSAP immunostaining is of particular concern because this approach may result in a method that is not sufficiently sensitive to detect the reduced PSA and PSAP expression associated with high grade prostate cancer.

Acid Phosphatase↗

Variations in the processing of prostatic needle cores in the UK; what is safe?

AIMS: To determine the variation in the processing of prostatic needle cores in the UK and to compare the results with suggested guidelines. METHODS: A standard questionnaire was sent to 210 pathology departments enquiring about current practices. RESULTS: One hundred and thirty replies were received, which showed considerable variation in current methods. The number of cores received for each case ranged from three to 21, with the number of cores processed for each cassette varying from one to 10. Sixty per cent of centres used no special embedding techniques, and the number of sections cut for each case varied from two to 128, with a median of 12 sections for each case. Forty two per cent of laboratories did not take spare slides for immunochemistry. CONCLUSIONS: There is great variation in the processing of prostatic cores in the UK. In particular, some laboratories process a large number of cores in each cassette and do not use special embedding techniques. At present there are no established guidelines for the processing of these specimens. Enhanced techniques may well increase the sensitivity of the test but would increase the workload and costs to the pathology department. In view of the increasing workload from these specimens, a consensus for their optimum processing is required.

Biopsy, Needle↗

DNA topoisomerase I and II expression in drug resistant germ cell tumours.

A small number of testicular germ cell tumours are refractory to current chemotherapy regimens. DNA topoisomerase I is the target for several new drugs and a potential candidate treatment for chemorefractory germ cell tumours. DNA topoisomerase II alpha is the target for etoposide, which is currently used regularly in germ cell tumour treatment. The expression of DNA topoisomerase I and II alpha were therefore assessed immunohistochemically in a range of testicular tumours, especially those with persistent malignant elements on retroperitoneal lymph node dissection. Pre-chemotherapy orchidectomy specimens were matched with post-chemotherapy retroperitoneal lymph node dissections to examine changes in expression. There was considerable variation in the expression of topoisomerase I in different tumour types. Both yolk sac tumours and teratoma, mature showed universal expression of topoisomerase I, while 38% of seminomas and 30% of embryonal carcinomas were positive. Strong topoisomerase II alpha expression was found in embryonal carcinoma. There was a negative correlation between topoisomerase I and II alpha expression (P=0.004) and downregulation of topoisomerase II alpha after chemotherapy (P=0.02). Topoisomerase I expression appears to increase in those cases with residual teratoma, mature, but is largely unchanged in those cases remaining as embryonal carcinoma. These results suggest that topoisomerase I inhibitors may be useful in chemorefractory germ cell tumours, especially yolk sac tumours and where there are unresectable residual teratoma, mature deposits.

Antineoplastic Combined Chemotherapy Protocols↗

Prediction of relapse after lymph node dissection for germ cell tumours: can salvage chemotherapy be avoided?

Salvage chemotherapy has been used by some oncology centres for patients with residual malignant or immature elements in retroperitoneal lymph node dissections removed for metastatic non-seminomatous germ cell tumours. However, surveillance of these patients shows that many are cured by surgery alone. 118 retroperitoneal lymph node dissections for metastatic non-seminomatous germ cell tumours were reviewed and the morphology seen within them was quantified. 28 of these had immature or malignant elements and had been treated by surveillance before administration of further chemotherapy. The proliferation rate in these cases was assessed by immunochemistry. The proliferation index and the amount of embryonal carcinoma (EC) were both predictors of recurrence and therefore the need for further chemotherapy. Patients with greater than 25% of EC had an 84% chance of relapse and those with a Ki-67 index of greater than 50% had a 71% chance of relapse. The two tests had a positive predictive value of 83% and 71%, respectively. Patients with such a high risk of recurrence could be considered for post-operative adjuvant therapy at this point whilst others would be suitable for a watchful waiting approach.

Adult↗

Loss of CD30 expression in metastatic embryonal carcinoma: the effects of chemotherapy?

AIMS: CD30 has been shown to be consistently strongly expressed in embryonal carcinomas. Our aim was to examine changes in CD30 expression in embryonal carcinomas before and after treatment with chemotherapy. METHODS AND RESULTS: One hundred and eighteen retroperitoneal lymph node dissections from patients with metastatic germ cell tumours were reviewed. Seventeen contained embryonal carcinoma deposits. In nine cases, the matching pre-chemotherapy orchidectomy specimens were available. The cases were immunohistochemically stained for CD30. All nine pre- chemotherapy orchidectomy specimens showed embryonal carcinoma and stained strongly positively for CD30. However, only four out of nine of the matched post-chemotherapy retroperitoneal lymph node dissection specimens and a total of six out of 17 (35%) with embryonal carcinoma deposits stained for CD30. Ten seminomas were negative for CD30. Loss of CD30 did not appear to influence the relapse rate of the patients. CONCLUSIONS: Loss of CD30 expression occurs frequently in metastatic embryonal carcinomas after chemotherapy. This finding has implications in the use of CD30 in the diagnosis of metastatic non-seminomatous germ cell tumours and suggests that chemotherapy may alter the immunophenotype of embryonal carcinoma while retaining its characteristic histological appearances.

Carcinoma, Embryonal↗

Spermatic cord rhabdomyoma.

A 67-year-old man presented with a scrotal swelling. Intraoperatively, this swelling was found to arise from the spermatic cord structures and was completely excised. Histopathology revealed a rhabdomyoma arising from the cord. The patient has had no evidence of recurrence in the past 24 months. We present the various types of rhabdomyomas and discuss the differential diagnosis for a spermatic cord swelling.

Aged↗

Clear cell carcinoma of the ovary arising in a mucinous cystadenoma.

A 57 year old woman presented complaining of increasing abdominal swelling of six months duration. A mixed solid cystic left ovarian tumour measuring 24 cm in diameter was excised. Histology showed numerous cysts lined by benign mucinous epithelium blending imperceptibly into borderline clear cell and mucinous areas that in turn merged with an invasive clear cell carcinoma. To the best of our knowledge, this is the first reported case of clear cell carcinoma arising in a mucinous cystadenoma. The implications for the previously postulated pathogenesis of these tumours are discussed.

Adenocarcinoma, Clear Cell↗

The effects of maternal protein deprivation on the fetal rat pancreas: major structural changes and their recuperation.

There is evidence that low birth weight and poor growth in early life cause a long-term predisposition to non-insulin-dependent diabetes. Morphological changes were assessed in fetal rat pancreas subjected to both pre- and post-natal maternal protein deprivation (LP). Further groups were subjected to purely prenatal maternal protein deprivation (preLP) and purely postnatal maternal protein deprivation (postLP), as well as a control group. The results show that the LP and postLP groups had fewer but larger islets than the control group, while the preLP group had more numerous, smaller islets. All three low protein groups had more irregularly shaped islets than the control group. There was a reduction in the amount of beta cells within each islet in all three protein-deprived groups. The LP and postLP groups showed a reduction in the percentage of islet tissue and beta cells per pancreas, but the percentage of islet tissue expressed per unit body weight was similar in all four groups. These results show that in maternal protein deprivation, homeostatic mechanisms ensure a constant amount of pancreatic endocrine tissue per unit of body weight. However, there remain major structural changes in the size, shape, and composition of the islets. These results support the theory that early development profoundly affects the structure of the pancreas and may play a role in the later development of adult diseases, such as non-insulin-dependent diabetes mellitus.

Animal Nutritional Physiological Phenomena↗

Angiolymphoid hyperplasia with eosinophilia in the colon: a novel cause of rectal bleeding.

Angiolymphoid hyperplasia with eosinophilia (epithelioid haemangioma) is an uncommon but distinctive lesion seen principally in the skin. A case of severe gastrointestinal haemorrhage in a 63 year old male is reported, which necessitated a right hemicolectomy. A lobulated nodule was seen macroscopically that had the histological appearance of angiolymphoid hyperplasia with eosinophilia, with sheets of lymphocytes and eosinophils associated with many vessels showing plump and pleomorphic endothelial cells. This is the first reported case of this entity in the large intestine.

Angiolymphoid Hyperplasia with Eosinophilia↗

Alkaline encrusted cystitis associated with malakoplakia.

Alkaline encrusted cystitis is a rare inflammatory condition of the bladder which has been reported sporadically over the past 80 years. It is caused by infection with urea splitting organisms leading to the deposition of inorganic salts on to the surface of the bladder. We present three cases of alkaline encrusted cystitis. In two cases the encrusted area was associated with foci of malakoplakia. The third case occurred in a patient who had received chemotherapy for acute lymphoblastic leukaemia. To our knowledge, these are the first cases of malakoplakia associated with alkaline encrusted cystitis. These two conditions have a number of clinical and aetiological similarities, and may have more in common than has been previously thought.

Adolescent↗

Symptomatic vitamin E deficiency diagnosed after histological recognition of myometrial lipofuscinosis.

We report a 44-year-old woman in whom intestinal bypass for obesity at age 23 resulted in chronic malabsorption. After hysterectomy for menorrhagia due to atypical endometrial hyperplasia, the finding of myometrial lipofuscinosis led to a demonstration of vitamin E deficiency. Vitamin E supplementation led to an unexpected improvement in the unsteadiness of gait and slurring of speech of which she had also complained. We suggest that supplementation with vitamin E should be routine in all patients with persistent severe steatorrhoea.

Adult↗