Entonox analgesia for prostatic biopsy.

We performed a prospective randomised double-blind study to evaluate the efficacy of Entonox (nitrous oxide) as an analgesic for trans-rectal ultrasound (TRUS) and prostate biopsy. A total of 50 patients breathed either Entonox or air during sextant prostatic biopsies all of which were performed by the same surgeon. The degree of pain experienced was recorded on a 100 mm visual analogue pain scale. A total of 17 further patients were excluded from the study because they wished to drive home after TRUS. Most patients breathing air experienced moderate pain (median pain score 34), whereas those breathing Entonox experienced minimal pain (median pain score 11). Two patients who used Entonox and one breathing air experienced severe pain. We conclude that patients undergoing prostate biopsy without analgesia experience moderate pain and this can be reduced significantly by using Entonox.

An interstitial light assembly for photodynamic therapy in prostatic carcinoma.

OBJECTIVE: To develop an interstitial laser light delivery system using multiple optical fibres for photodynamic therapy (PDT) in the treatment of prostate cancer. PATIENTS AND METHODS: A laser beam was divided equally with a 1 x 4 fibre splitter to deliver PDT simultaneously through four 2-cm long, flexible cylindrical optical diffusers. Biplanar transrectal ultrasonography (TRUS) and a template were used to position the optical fibres percutaneously. In vivo measurements of light penetration depth (1/micro[eff] ) in prostate tissue were made in seven patients, using a sheathed isoprobe to measure light fluence rates at varying radial distances from the diffuser. The prostate was fixed with stabilization needles to minimize displacement during needle placement. RESULTS: The mean (sd, range) micro(eff) in the prostates of the seven patients was 0.35 (0.07, 0.22-0.44) mm-1, which produced closely parallel slopes of light attenuation. However, there was up to a 10-fold variation in absolute light levels at the same diffuser-detector separation distances amongst the seven patients, probably caused by blood pooling around the diffuser light source. A similar problem around the isoprobe detector was overcome by sheathing the probe in clear plastic tubing. By stabilizing the prostate, the optical fibre positioning was precise to within 2 mm. CONCLUSION: Although this light delivery and TRUS assembly were developed for clinical PDT in the prostate, the same instrumentation can be used reliably for in vivo light-penetration studies. Haemorrhage was unpredictable and highlighted one of the main problems which needs to be overcome.

Interstitial photodynamic therapy in the canine prostate.

OBJECTIVE: To determine the depth of tissue destruction and the minimum light dose required for necrosis in interstitial photodynamic therapy (PDT), as a prerequisite for the investigational therapy of patients. MATERIALS AND METHODS: Seven adult beagle dogs were given 2 mg/kg of the photosensitizer Photofrin intravenously and two controls received none. After 24 h, 450 J/cm of 630 nm wavelength laser light was delivered interstitially to the prostate via a 2 cm long diffuser fibre. Seven single-fibre treatments were performed in five sensitized dogs and two single-fibre treatments in the controls. The two remaining sensitized dogs had two fibres placed 10 mm apart within the prostate to determine the coalescence of PDT lesions. The penetration depth of light was measured in all prostates, and after PDT the extent of necrosis was assessed histologically. RESULTS: The mean (standard deviation, SD) radius of PDT destruction around each diffuser was 5.3 (1.4) mm and PDT lesions overlapped in prostates treated with two fibres placed 10 mm apart. There was no observable tissue damage in the controls. The mean (SD) minimum light dose required for PDT necrosis was 84 (64) J/cm2. Differences among animals in the light penetration depth were small, with a mean of 2.14 (0.2) mm, and did not correlate with the depth of necrosis (P = 0.07). Bleeding around the optical diffuser fibre impeded light penetration. CONCLUSION: Interstitial PDT in the canine prostate using Photofrin produced modest volumes of tissue necrosis. The minimum light dose required to induce necrosis was variable because bleeding was unpredictable in relation to the optical fibre.

In situ comparison of 665 nm and 633 nm wavelength light penetration in the human prostate gland.

The depth of treatment in photodynamic therapy (PDT) of tumors varies with the wavelength of light activating the photosensitizer. New generation photosensitizers that are excited at longer wavelengths have the potential for increasing treatment depths. Tin ethyl etiopurpurin (SnET2), a promising second-generation photosensitizer is maximally activated at 665 nm, which may be significantly more penetrating than 633 nm light currently used with porphyrins in PDT. The penetration of 665 nm and 633 nm wavelength red light in the prostate gland was compared in 11 patients undergoing prostatic biopsies for suspected prostatic cancer. Interstitial optical fibers determined the light attenuation within the prostate gland. Of the 11 patients, 7 had dual wavelength and 4 had single wavelength studies. The mean attenuation coefficients, mueff, for 665 nm and 633 nm wavelength light were 0.32 +/- 0.05 mm-1 and 0.39 +/- 0.05 mm-1, respectively, showing a statistically significant difference (P = 0.0003). This represented a 22% increase in the mean penetration depth and at 10 mm from the delivery fiber there was 1.8 times as much 665 nm light fluence than 633 nm. The mean mueff at 665 nm for benign and malignant prostate tissue were similar (P = 0.42), however, there was significant interpatient variation (mueff ranging from 0.24 to 0.42 mm-1) reflecting biological differences of therapeutic importance. The enhanced light fluence and penetration depth with 665 nm light should allow significantly larger volumes of prostatic tissue to be treated with SnET2-mediated PDT.

In vivo laser light distribution in human prostatic carcinoma.

The extent of laser light diffusion within prostatic tumor is of major importance in the treatment of localized prostatic cancer with photodynamic therapy (PDT). The penetration of 633 nm. wavelength red light was studied in eleven patients with suspected prostatic cancer using a novel method suitable for in situ measurements. Light delivery and detector fiber, placed interstitially within the gland, determined light attenuation at different interfiber separations. Of 11 patients, 10 had bilateral and 1 had single lobe studies. The mean +/- the standard error of the mean attenuation coefficients (sigma eff) for benign and malignant prostate tissue were 0.35 +/- 0.02 mm-1 and 0.36 +/- 0.02 mm-1, respectively, indicating similar optical densities (p = .58). Patients with bilateral lobe involvement showed little intraglandular variation in sigma eff (p = 0.23). However, there was interpatient variation (sigma eff = 0.28 to 0.48 mm-1) reflecting biological differences which, though therapeutically important, were not statistically significant (p = 0.057). This study showed that treatment requires individualization and predicted that 4 cylindrical diffusers are expected to destroy 25 ml. of prostatic tumor with PDT.

Optimization of multifiber light delivery for the photodynamic therapy of localized prostate cancer.

The understanding of light distribution within the target organ is essential in ensuring efficacy and safety in photodynamic therapy (PDT). A computer simulator of light distribution in prostatic tissue was employed for optimizing dosimetry for PDT in localized prostatic cancer. The program was based on empirically determined light distributions and optical constants and an assumed fluence rate differential from fiber source to necrosis periphery. The diffusion theory approximation to the Boltzmann transport equation was the applicable formulation relevant to prostatic tissue, which has a high albedo with forward-scattering characteristics. Solving this equation of diffusive transfer for the appropriate fiber geometry yielded the energy fluence distributions for cleaved fiber and cylindrical diffuser light delivery. These distributions, confirmed by our measurements, show a 1/r and 1/square root of r dependency (r = distance from light source) of the fluence phi (r) for the cleaved fiber and diffuser, respectively. This manifests itself by the tighter spacing of energy fluence isodoses in the case of the cleaved fiber. It was predicted that for a typical PDT regime a single interstitially placed cleaved fiber would treat 0.05-0.72 cm3. Four parallel fibers improved the uniformity of light distribution and treatment volume, and an interfiber separation of 12 mm would be necessary to provide optimal overlap of PDT necrosis, treating 0.26-3.6 cm3. The cylindrical diffuser, however, could treat larger volumes, and it was predicted that four 3 cm long diffusers at an optimal separation of 25 mm would treat 25-88 cm3 of prostatic tissue.

The uptake of porphyrin and zinc-metalloporphyrin by the primate prostate.

The relative distribution of sensitizer drugs in the prostate and its contiguous organs is of importance in the treatment of localized prostatic cancer with photodynamic therapy. Using the primate model, whose prostate is both morphologically and physiologically homologous with its human counterpart, the distribution of hematoporphyrin derivative (HpD) amongst organs of urological interest was determined. Hematoporphyrin derivative levels were comparatively low in both caudal and cranial prostatic lobes (0.93-1.77 micrograms/g) and were similar to those in rectum, urethra and the skin. The reticuloendothelial organs, liver, spleen and also the kidney accumulated the highest quantities of porphyrin (4.76-9.8 micrograms/g, liver > spleen > kidney). Despite a high avidity of prostatic tissue for zinc, a zinc-metalloporphyrin (Zn-HpD) did not concentrate selectively in the prostate. The results are of clinical value in view of the homology between the primate and the human.

Levels of prostate specific antigen that predict skeletal spread in prostate cancer.

The ability of serum prostate specific antigen (PSA) and serum acid phosphatase (SAP) to identify skeletal spread was evaluated in untreated patients with prostatic cancer. Twenty patients with scintigraphic evidence of metastatic disease in bone (M1) at diagnosis were compared with 50 untreated patients in whom scans were repeatedly negative during long-term surveillance. Using the present laboratory upper limit of normal (ULN) of 3 iu/l, the sensitivity and specificity of SAP for M1 disease were 80 and 86% respectively. Stepwise discriminant analysis demonstrated that SAP was able to stage patients correctly (bone scan positive or negative) with 81% predictive accuracy at an optimum cut-off limit of 4.6 iu/l. By contrast, whilst PSA (Hybritech) was 100% sensitive for skeletal disease at 10 ng/ml--at the expense of poor (36%) specificity--analysis determined that an optimum cut-off limit of 58 ng/ml led to 79% predictive accuracy for disease in bone. It was concluded that PSA levels > 58 ng/ml are highly indicative of spread to the skeleton, even in the absence of radiological or scintigraphic evidence of metastases.

Photodynamic therapy for localised prostatic cancer: light penetration in the human prostate gland.

We are investigating the feasibility of photodynamic therapy in the treatment of localised prostatic cancer. Of major importance in this form of treatment is the extent to which light penetrates the target organ; hence, our interest in the optical properties of the human prostate gland. We obtained three whole prostates from autopsies of patients who died of non-urological causes. Red light was launched interstitially and detector fibres measured light intensity as a function of distance from the delivery fibre end. The optical constants derived from the three prostates were almost identical and indicated that light was predominantly scattered rather than absorbed (mean absorption and scattering coefficients 0.07 +/- 0.02 mm.-1 and 0.86 +/- 0.05 mm.-1 respectively). In a comparison of the tissue penetration by four different wavelengths, 633 nm red light was found to be transmitted best. Light propagation in the heavily absorbing tissue of the human liver was 4.3 times poorer than in the prostate. Such a combination of low absorption and high scattering characteristics in prostatic tissue would enhance the effectiveness of PDT. The optical constants derived will enable "light treatment planning" in patients with prostatic cancer.

Staging laparotomy in early Hodgkin's disease: a surgical view.

Fifty consecutive patients with early Hodgkin's disease underwent staging laparotomy. There were no deaths and most complications were minor. As a consequence, 17 (34%) patients were upstaged from clinical stage I or II to pathological stage III or IV. Subdiaphragmatic disease was found in five out of 22 patients with nodular sclerosing, seven out of ten with lymphocyte predominant and four out of 13 patients with mixed cellularity histological type. The age, sex, preoperative clinical stage and mediastinal involvement did not correlate with the presence of intra-abdominal disease. Among 15 patients with a normal preoperative computed tomography (CT) scan, nine had intra-abdominal disease at laparotomy and all three patients with suggested subdiaphragmatic involvement by the CT scan examination were clear. The surgeon's ability to diagnose early involvement at laparotomy was also limited. There seems to be a continued need for staging laparotomy to ensure adequate treatment of one-third of patients with early Hodgkin's disease.

Left ventriculo-colic fistula--a late complication of colonic interposition for the oesophagus.

An 18 year old man developed recurrent haematemesis 12 years after colonic interposition for corrosive injury to the oesophagus. A colonic ulcer close to the cologastric anastomosis appeared to have fistulated into the cavity of the left ventricle. This so far unreported complication needs to be considered when patients who have had coloesophageal substitution present with gastrointestinal bleeding.