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%).

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.

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.

Oxygen exchange in the isolated, arrested guinea pig heart: theoretical and experimental observations.

A model of oxygen transport in perfused myocardial tissue is presented. Steady-state conditions are assumed in order to mimic the metabolic rate of the arrested heart. The model incorporates Michaelis-Menten dependence of mitochondrial oxygen consumption, oxymyoglobin saturation and oxyhemoglobin saturation on oxygen partial pressure (PO2). The transport equations model both the advective supply of oxygen via the coronary circulation and the diffusive exchange of oxygen between tissues and environment across the epicardial and endocardial surfaces. The left ventricle is approximated by an axisymmetric prolate spheroid and the transport equations solved numerically using finite element techniques. Solution yields the PO2 profile across the heart wall. Integration of this profile yields the simulated rate of metabolic oxygen uptake determined according to the Fick principle. Correction for the diffusive flux of oxygen across the surfaces yields the simulated true metabolic rate of oxygen consumption. Simulated values of oxygen uptake are compared with those measured experimentally according to the Fick principle, using saline-perfused, Langendorff-circulated, K(+)-arrested, guinea pig hearts. Four perfusion variables were manipulated: arterial PO2, environmental PO2, coronary flow and perfusion pressure. In each case agreement between simulated and experimentally determined rates of oxygen consumption gives confidence that the model adequately describes the advective and diffusive transport of oxygen in the isolated, arrested, saline-perfused heart.

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.

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.

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.

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.