Dynamic contrast-enhanced MRI for prostate cancer localization.

Radiotherapy dose escalation improves tumour control in prostate cancer but with increased toxicity. Boosting focal tumour only may allow dose escalation with acceptable toxicity. Intensity-modulated radiotherapy can deliver this, but visualization of the tumour remains limiting. CT or conventional MRI techniques are poor at localizing tumour, but dynamic contrast-enhanced MRI (DCE-MRI) may be superior. 18 patients with prostate cancer had T(2) weighted (T2W) and DCE-MRI prior to prostatectomy. The prostate was sectioned meticulously so as to achieve accurate correlation between imaging and pathology. The accuracy of DCE-MRI for cancer detection was calculated by a pixel-by-pixel correlation of quantitative DCE-MRI parameter maps and pathology. In addition, a radiologist interpreted the DCE-MRI and T2W images. The location of tumour on imaging was compared with histology, and the accuracy of DCE-MRI and T2W images was then compared. Pixel-by-pixel comparison of quantitative parameter maps showed a significant difference between the benign peripheral zone and tumour for the parameters K(trans), v(e) and k(ep). Calculation of areas under the receiver operating characteristic curve showed that the pharmacokinetic parameters were only "fair" discriminators between cancer and benign gland. Interpretation of DCE-MRI and T2W images by a radiologist showed DCE-MRI to be more sensitive than T2W images for tumour localization (50% vs 21%; p = 0.006) and similarly specific (85% vs 81%; p = 0.593). The superior sensitivity of DCE-MRI compared with T2W images, together with its high specificity, is arguably sufficient for its use in guiding radiotherapy boosts in prostate cancer.

Sentinel lymph node biopsy using dynamic lymphoscintigraphy combined with ultrasound-guided fine needle aspiration in penile carcinoma.

The purpose of this study was to assess the utility of sentinel lymph node lymphoscintigraphy (SLNL) and ultrasound-guided fine needle aspiration cytology (FNAC) in patients with penile carcinoma. A prospective study was undertaken of 64 patients with stage T1 (or greater) clinically N0 squamous cell carcinoma of the penis. Patients underwent SLNL and bilateral groin ultrasonography with or without FNAC. Following intradermal blue dye, patients underwent unilateral or bilateral sentinel lymph node excision biopsy (SNB). 17 patients had sentinel nodes that contained metastases (21 nodal basins). Lymphatic drainage was demonstrated in all patients by lymphoscintigraphy. Bilateral drainage was seen in 57/64 patients. 61/64 patients had ultrasonography of the inguinal basins on the same day as FNAC of 38 basins. FNAC showed malignancy in eight basins. FNAC was negative in six basins, which were subsequently shown to be positive following SNB. 82 inguinal basins did not warrant FNAC by ultrasound criteria, of which 5 contained metastases at SNB. The sensitivity and specificity of ultrasonography was 74% and 77%, respectively. The positive and negative predictive values were 37% and 94%, respectively. Two patients had a negative initial SNB; however, ultrasonography identified a metastatic node and re-evaluation of the sentinel node confirmed micro-metastases. There has been no evidence of recurrence in any patients with negative SNB (during 6-28 months' follow-up). In conclusion, when investigating clinically stage N0 penile cancer, the combination of SNB and groin ultrasonography, with or without FNAC, identifies accurately those with occult nodal metastases. Ultrasonography alone is not adequate as a staging technique, and SNB alone might miss between 5% and 10% of metastases.

Squamous cell carcinoma of the penis in a patient with chronic isolated penile lymphoedema.

Squamous cell carcinoma arising in tissue affected by chronic lymphoedema is rare. We describe, to our knowledge, the first documented case of penile squamous cell carcinoma arising in a patient with a history of idiopathic chronic penile lymphoedema. Patients with chronic lymphoedema should be actively followed for possible malignant changes. We discuss the management and possible aetiology of this unusual case.

Construction of tissue microarrays from prostate needle biopsy specimens.

Needle biopsies are taken as standard diagnostic specimens for many cancers, but no technique exists for the high-throughput analysis of multiple individual immunohistochemical (IHC) markers using these samples. Here we present a simple and highly reliable technique for constructing tissue microarrays (TMAs) from prostatic needle biopsies. Serial sectioning of the TMAs, called 'Checkerboard TMAs', facilitated expression analysis of multiple proteins using IHC markers. In total, 100% of the analysed biopsies within the TMA both preserved their antigenicity and maintained their morphology. Checkerboard TMAs will allow the use of needle biopsies (i) alongside other tissue specimens (trans-urethral resection of prostates and prostatectomies in the case of prostate cancer) in clinical correlation studies when searching for new prognostic markers, and (ii) in a diagnostic context for assessing expression of multiple proteins in cancers from patients prior to treatment.

Prostatic intraepithelial neoplasia: a risk factor for prostate cancer.

Prostatic Intraepithelial Neoplasia (PIN) is an increasingly common finding at ultrasound guided prostate biopsy, with the high grade form (HGPIN) thought to be "precancerous". With the more widespread use of extended biopsy protocols, taking sometimes up to 14 cores or more, the incidence of HGPIN can be up to 25%. Histologically, it has many features in common with cancer of the prostate and has been shown to be both associated with cancer at the time of its finding and predictive for the development of prostate cancer in the future. Basic science research has demonstrated genes common specifically to both prostate cancer and HGPIN and immunostaining studies of microvessel density may help to differentiate HGPIN from lower risk PIN. There are no active treatments for HGPIN although there are trials to assess the effectiveness of hormonal therapy and nutritional supplements. Currently most urologists recommend that patients should be followed at 6 monthly intervals with regular PSA and repeat biopsies as indicated.

Signet ring cell carcinoma in the prostate.

Metastases to the prostate gland are rare and often found in the context of widespread metastatic disease. We report an unusual case of primary gastric signet ring cell adenocarcinoma (SRCC) diagnosed over 1 year after treatment for metastatic disease in the prostate.

Potential improvements in the therapeutic ratio of prostate cancer irradiation: dose escalation of pathologically identified tumour nodules using intensity modulated radiotherapy.

The potential of intensity modulated radiotherapy (IMRT) to improve the therapeutic ratio in prostate cancer by dose escalation of intraprostatic tumour nodules (IPTNs) was investigated using a simultaneous integrated boost technique. The prostate and organs-at-risk were outlined on CT images from six prostate cancer patients. Positions of IPTNs were transferred onto the CT images from prostate maps derived from sequential large block sections of whole prostatectomy specimens. Inverse planned IMRT dose distributions were created to irradiate the prostate to 70 Gy and all the IPTNs to 90 Gy. A second plan was produced to escalate only the dominant IPTN (DIPTN) to 90 Gy, mimicking current imaging techniques. These plans were compared with homogeneous prostate irradiation to 70 Gy using dose-volume histograms, tumour control probability (TCP) and normal tissue complication probability (NTCP) for the rectum. The mean dose to IPTNs was increased from 69.8 Gy to 89.1 Gy if all the IPTNs were dose escalated (p=0.0003). This corresponded to a mean increase in TCP of 8.7-31.2% depending on the alpha/beta ratio of prostate cancer (p<0.001), and a mean increase in rectal NTCP of 3.0% (p<0.001). If only the DIPTN was dose escalated, the TCP was increased by 6.4-27.5% (p<0.003) and the rectal NTCP was increased by 1.8% (p<0.01). In the dose escalated DIPTN IMRT plans, the highest rectal NTCP was seen in patients with IPTNs in the posterior peripheral zone close to the anterior rectal wall, and the lowest NTCP was seen with IPTNs in the lateral peripheral zone. The ratio of increased TCP to NTCP may represent an improvement in the therapeutic ratio, but was dependent on the position of the IPTN relative to the anterior rectal wall. Improvements in prostate imaging and prostate immobilization are required before clinical implementation would be possible. Clinical trials are required to confirm the clinical benefits of these improved dose distributions.

Improving glandular coverage during prostate biopsy using a long-core needle: technical performance of an end-cutting needle.

OBJECTIVE: To compare the technical performance of a 33-mm core-length biopsy needle with that of the standard 18 mm needle, as many prostate cancers are isoechoic and in large prostates the tissue coverage with the 18 mm needle is inadequate. PATIENTS AND METHODS: A 33-mm core length BioPince VSL disposable needle (Amedic, Sweden) and a standard TruCut 18 mm needle (Medical Device Technology Inc., FL, USA) were used to take prostatic biopsies in two groups of 15 patients. The following variables were assessed for each group: mean core length, core quality, capsular coverage (one or both capsules within the specimen), and side-effects in the first week after biopsy (for the BioPince group, surveyed using a self-completed questionnaire). The results were compared with historical data from a group of 30 patients biopsied using the standard needle. RESULTS: For the BioPince and standard groups the mean (sd) core length was 19.4 (8.9) and 14.9 (5.1) mm, respectively. Four needles in the BioPince group failed to capture a sample, requiring needle replacement. The samples were fragmented in 15 of 90 (17%) and 41 of 90 (46%) biopsies in the BioPince and standard groups, respectively (P < 0.05). Specimens had both capsules present in five of 90 (6%) and four of 90 (4%), respectively. Within 7 days minor bleeding was the most common side-effect. Pain after biopsy was the only symptom showing a significant difference between the groups, at six of 15 and none (P = 0.001), respectively. The incidence of haematuria, haematospermia and rectal bleeding was similar in the two groups (P > 0.05), but fever more common (three vs none) in the BioPince group (P = 0.06). CONCLUSION: When set at a 33-mm stroke length, the BioPince needle increases the mean core length by 30%, with less fragmentation than a standard 18 mm needle. However, it has a significant failure rate for capture (27% needle replacement rate), slightly greater morbidity (pain and possibly fever) and shows no advantage in capsular coverage. Therefore, there are shortcomings with this end-cutting needle when used at 33 mm core length.

Progression of Gastric Mucosal Dysplasia of the Postgastrectomy Stomach.

Gastric cancer, if diagnosed at the symptomatic stage, has a poor prognosis, with an overall 5 year survival of about 5%. The surgical treatment of early gastric cancer increases this 5-year survival rate to 90%. In Japan, endoscopic surveillance has increased the proportion of gastric cancer detected at an early stage from 15% in 1960 to 50% in 1985, and the overall 5 year survival has been increased from 35% to 70%. Mass screening in Japan is worthwhile because the incidence of gastric cancer is about 80 cases per 100,000 population per annum (age standardized). But in other countries where the incidence is much lower the case for mass screening is weak and selective screening of those at high risk is advocated.

Progression of gastric mucosal dysplasia of the postgastrectomy stomach.

Gastric cancer, if diagnosed at the symptomatic stage, has a poor prognosis, with an overall 5 year survival of about 5%. The surgical treatment of early gastric cancer increases this 5-year survival rate to 90%. In Japan, endoscopic surveillance has increased the proportion of gastric cancer detected at an early stage from 15% in 1960 to 50% in 1985, and the overall 5 year survival has been increased from 35% to 70%. Mass screening in Japan is worthwhile because the incidence of gastric cancer is about 80 cases per 100,000 population per annum (age standardized). But in other countries where the incidence is much lower the case for mass screening is weak and selective screening of those at high risk is advocated.

Mycobacterium vaccae (SRL172): a potential immunological adjuvant evaluated in rat prostate cancer.

OBJECTIVE: To evaluate the potential of heat-killed Mycobacterium vaccae (SRL172) as a nonspecific immunostimulant and as an adjuvant to whole tumour cell vaccination in the rat model of prostate cancer. MATERIALS AND METHODS: SRL172 was used as a vaccine in the prevention and treatment of subcutaneous tumours in rats. Prevention experiments were conducted using subcutaneous MAT-LyLu tumours in Copenhagen rats, comparing vaccination with SRL172 alone, SRL172 plus autologous cells, and bacille Calmette-Guèrin (BCG) plus autologous cells before tumour implantation. Treatment experiments were conducted using subcutaneous MAT-LyLu tumours in the Copenhagen rat and subcutaneous PAIII tumours in the Lobund-Wistar rat. Tumours were induced by subcutaneous injection with tumour cells. Animals were then vaccinated with autologous cells, autologous cells plus SRL172, or SRL172 alone. RESULTS: SRL172 was effective as an adjuvant to autologous whole tumour cell vaccination in the prevention of MAT-LyLu tumours and the survival benefit was equivalent to that provided when the adjuvant was live-attenuated BCG. SRL172 alone did not reduce tumour take or tumour growth in this model and neither strategy was effective in delaying the growth of established MAT-LyLu tumours. In the Lobund-Wistar rat vaccination with autologous whole tumour cells and SRL172 significantly delayed the growth of established tumours. CONCLUSION: Mycobacterium vaccae deserves further evaluation as an adjuvant to whole tumour cell vaccination in a phase I clinical trial in patients with prostate cancer.

Human cytomegalovirus and acute rejection after heart transplantation are not directly associated.

Retrospective and prospective analyses of heart transplant recipients showed no significant association between acute rejection and the detection of cytomegalovirus (CMV) infection by culture or the polymerase chain reaction (PCR) for viral DNA, neither on grounds of the incidence of both conditions nor in relation to which was diagnosed first in the patient. Semiquantitative PCR of serial blood and endomyocardial biopsy specimens from individual patients revealed different patterns in the development of the viral DNA in the blood and the heart, also clear episodes of CMV infection in CMV antibody-negative recipients of hearts from CMV antibody-negative donors, none of whom went on to develop a CMV-specific antibody response. None of these findings was associated with the development of rejection in the patient. On the other hand, in those patients who did experience rejection, peak levels of CMV DNA in the blood and the heart were usually not reached until 6 weeks or more after transplantation, whereas in those in whom rejection was not detected at all during the period of observation, peak levels of CMV DNA were detected earlier, mainly within the first 6 weeks after transplantation. In several cases, the delayed increase in CMV DNA in those with rejection, albeit not the delay itself, was linked to treatment with steroids. These findings support the view that CMV infection and rejection are independent events, but that the timing of the infection, and whether or not rejection is detected, are indicative of the general status of the immune response in individual patients.

Gastric DNA content in postgastrectomy patients. Relationship to mucosal dysplasia.

BACKGROUND: Gastric mucosal cellular DNA content was assessed in patients who had undergone gastric surgery for peptic ulcer disease more than 20 years previously, with the aim of examining the relationship between abnormal DNA content and gastric mucosal dysplasia, as well as determining the effect of different types of surgery on DNA content. METHODS: Sixty-five subjects underwent upper gastrointestinal endoscopy. In each, six biopsies were taken from the stoma or antrum and graded for severity of dysplasia. Cellular DNA was quantified using a microprocessor-controlled image analysis system with a fast densitometer card on Feulgen-stained slides. DNA histograms were evaluated using the 2c deviation index (2cDI) for proliferative activity and the 4c exceeding rate (4cER) and the 5c exceeding rate (5cER) as indices of malignant potential. RESULTS: In subjects with Billroth II operations, all the above DNA criteria were higher than in Billroth I (P < 0.05), vagotomy and pyloroplasty (P < 0.001), and controls (P < 0.0001). DNA values increased as dysplasia progressed in severity (2cDI, Rs = 0.67; 4cER, Rs = 0.61; 5cER, Rs = 0.72; respectively, P < 0.0001). Among subjects with no dysplasia, more aneuploid cells were found in the Billroth II group, (p < 0.005) compared with the other types of operation. CONCLUSIONS: Cellular DNA content is abnormal at an early stage in dysplasia and may even predate it. Increasing values of abnormal DNA content are related to the severity of dysplasia. DNA analysis may be a useful additional tool in surveillance programs to select high-risk patients for screening.

Rapid processing in the management of prostatic cancer.

OBJECTIVE: To carry out rapid histological processing of prostatic biopsies for the management of patients who present with urinary retention or other urological problems, or with a suspected diagnosis of prostatic cancer. PATIENTS AND METHODS: Biopsies were taken from each of 26 patients who presented with urinary retention or other urological problems, or with a suspected diagnosis of prostatic cancer. The biopsies were processed in a Shandon Hypercenter using a 3-hour programme and were stained on a Shandon Linistainer automatic staining machine. The slides were reviewed both immediately and at weekly histopathology audit meetings. RESULTS: Results were available within 4 h of receipt of the specimen in the laboratory. One false negative, due to a sampling error at the time of biopsy, was identified. CONCLUSION: We believe that this facility is of benefit to both surgeon and patient and should be more widely available.

Prevalence of Helicobacter pylori infection and its effect on symptoms and non-steroidal anti-inflammatory drug induced gastrointestinal damage in patients with rheumatoid arthritis.

Non-steroidal anti-inflammatory drugs (NSAIDs) and Helicobacter (H pylori) are both associated with an increased risk of peptic ulceration and gastropathy. It is not known, however, if there is an interaction between these two agents, and thus whether or not screening for H pylori before NSAID treatment is of value. The aim of this study was to find out if H pylori potentiates the damaging effects of NSAIDs. Fifty two patients with rheumatoid arthritis requiring longterm NSAID treatment were studied. Dyspeptic symptoms were assessed according to a standardised questionnaire. Gastroscopy was performed after a one week washout period during which NSAIDs were discontinued. Gastric and duodenal mucosal damage was graded endoscopically. H pylori was identified by biopsy urease test and by histological tests. Investigations were repeated after one month's treatment with an NSAID. Patients with H pylori infection (n = 26) had a higher dyspeptic symptom score (p < 0.05). One patient with duodenal ulcer (H pylori +ve) and two with endoscopic gastritis (both H pylori +ve) were excluded from further study. Forty two subjects completed the study. After treatment there was a rise in the gastric damage score both in the H pylori +ve (p = 0.06) and the H pylori -ve (p < 0.005) groups. There was no difference in the extent of increase in grade or the final grade at the end of the treatment period between the H pylori +ve and -ve patients. It is concluded that H pylori infection is associated with increased dyspeptic symptoms in patients receiving NSAIDs but that it does not potentiate NSAID gastropathy.

Prostatic sarcoidosis. Review of genitourinary sarcoidosis.

Sarcoidosis is seen by the urologist only rarely but it may present a diagnostic and therapeutic dilemma. We describe a rare case of prostatic sarcoidosis. The literature relating to sarcoidosis throughout the genitourinary system is reviewed.

Post-operative retention associated with acute prostatic infarction.

Twenty-one patients with post-operative retention following unassociated surgery and requiring transurethral resection of the prostate were compared with patients with acute retention (control group). Histological evidence of acute prostatic infarction was significantly increased in the post-operative retention group. Prolonged operative hypotension was associated with acute prostatic infarction, as were smoking and pre-existing cardiovascular disease.