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Background: Intraoperative diagnosis of sentinel node metastases enables an immediate decision to proceed to axillary lymph node dissection, avoiding a second operation in node-positive women with breast cancer., Methods: An optical scanner was developed that interrogated the cut surface of bivalved, but otherwise unprocessed, sentinel lymph nodes with pulses of white light by elastic scattering spectroscopy (ESS). The scattered light underwent spectral analysis, and individual spectra were initially correlated with conventional histology to develop a diagnostic algorithm. This algorithm was used to create false colour-coded maps of scans from an independent set of nodes, and the optimal criteria for discriminating between normal and cancer spectra were defined statistically., Results: The discriminant algorithm was developed from a training set of 2989 spectra obtained from 30 metastatic and 331 normal nodes. Subsequent scans from 129 independent nodes were analysed. The scanner detected macrometastases (larger than 2 mm) with a sensitivity of 76 per cent (69 per cent including micrometastases) and specificity of 96 per cent., Conclusion: In this proof-of-principle study, the ESS results were comparable with current intraoperative diagnostic techniques of lymph node assessment., (Copyright (c) 2010 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.)

Background: Photodynamic therapy (PDT) reduces neointimal hyperplasia and negative remodelling following balloon injury in small and large animal models. This clinical study investigated the role of adjuvant PDT following femoral percutaneous transluminal angioplasty (PTA)., Methods: Eight PTAs in seven patients (two women) with a median age of 70 (range 59-86) years were performed with adjuvant PDT. All patients had previously undergone conventional angioplasty at the same site which resulted in symptomatic restenosis or occlusion between 2 and 6 months. Each was sensitized with oral 5-aminolaevulinic acid 60 mg/kg, 5-7 h before the procedure. Following a second femoral angioplasty, up to 50 J/cm2 red light (635 nm) was delivered to the angioplasty site via a laser fibre within the angioplasty balloon. Patients were kept in subdued light overnight and discharged the following day. Outcome was assessed by duplex imaging at 24 h, 1, 3 and 6 months and by intravenous digital subtraction angiography at 6 months. A peak systolic velocity ratio (PSVR) of more than 2.0 at the angioplasty site was taken to represent restenosis., Results: All patients tolerated the procedure well without adverse complications or death. All were rendered asymptomatic which was sustained throughout the study interval. All vessels remained patent and no lesion attained the duplex definition of restenosis. Median (interquartile range) PSVR across stenotic segments was 4.7 (3.7-5.7) before angioplasty, 1.1 (0.9-1.3) at 24 h and 1.4 (1.0-1.8) at 6 months after intervention (P = 0.04 compared with preoperative value)., Conclusion: This pilot study suggests that endovascular PDT is safe and may reduce restenosis follow- ing angioplasty. The data justify a randomized controlled trial.

This preliminary report describes the use of interstitial laser photocoagulation to manage small breast cancers. Forty-four patients were treated with a diode laser of 805 nm under local anaesthesia in the interval between diagnosis and surgery. Ultrasonography was used in 42 patients and computed tomography (CT) in two to place the fibre in the tumour and monitor laser effects. Laser-induced necrosis within the resected tumour varied from 0 to 25 mm in diameter. The presence of charring in the tumour around the fibre tip after treatment was associated with significantly larger diameters of necrosis than when charring did not occur (median 13 versus 6 mm, P = 0.002). Precharring the fibre resulted in a more predictable diameter of necrosis (median 14 mm). Ultrasonography was inaccurate in assessing laser damage; dynamic CT and magnetic resonance imaging may be of more use. Interstitial laser photocoagulation is simple and safe, and can produce necrosis of a reasonably predictable extent.

Photodynamic therapy (PDT) is often thought to be able to effect selective tumour necrosis. This therapeutic selectivity, based on transient differences in tumour: normal tissue photosensitizer concentration ratios, is rarely useful clinically in extracranial tumours, although PDT itself may be of value by virtue of the nature of the damage produced and healing of normal tissue by regeneration. This report describes the effects of PDT on normal pancreas and chemically induced pancreatic cancers in the hamster, where a different mechanism of selective necrosis may be seen. Photosensitizer distribution in normal and neoplastic pancreas was studied by chemical extraction and fluorescence microscopy. Correlation of distribution studies with necrosis produced by PDT shows that the photodynamic dose (product of tissue concentration of sensitizer and light dose) threshold for damage is seven times as high for normal pancreas as for pancreatic cancer. Tumour necrosis extended to the point where tumour was invading normal areas without damaging the normal tissue. In rat colonic cancer, photodynamic dose thresholds in tumour and normal tissue are similar and so such marked selectivity of necrosis is not possible. The reason for this selectivity in the pancreas is not clear, but recent evidence has suggested a difference in response to PDT between normal and neoplastic pancreatic cell lines and the presence of a singlet oxygen scavenger in normal pancreas is postulated. Furthermore, the present fluorescence microscopy studies suggest that tumour stroma contains the highest level of photosensitizer and thus receives the highest photodynamic dose during PDT. These results suggest a possible role for PDT in treating small pancreatic tumours or as an adjuvant to other techniques, such as surgery, that reduce the main bulk of tumours localized to the pancreas.

Multiple four-fibre low-power interstitial laser hyperthermia was performed in the canine liver to establish the parameters with which large areas of thermal necrosis could be made. Using 1.5 W for 670 s (4020 J in total) and a fibre spacing of 1.5 cm, lesions with dimensions of 3.6 x 3.1 x 2.8 cm were achieved in 75 per cent of those attempted. There was no mortality and a low morbidity rate. These lesions could be visualized in both their development and resolution using ultrasonography. Healing occurred by 1 year. Temperatures in the centre of the heated region were 60 degrees C, which is more than enough to cause thermal cell death. There was good correlation between the temperatures recorded, the sonographic changes seen, and the pathological evidence of necrosis. Multiple-fibre low-power interstitial laser hyperthermia performed with ultrasonic guidance may be of use in the treatment of liver tumours.

Conventional palliative management of inoperable focal hepatic tumours remains unsatisfactory. Interstitial techniques such as cryotherapy, alcohol injection, low power laser hyperthermia and interstitial radiotherapy offer alternative approaches. Cryotherapy is an effective and precise technique for inducing tumour necrosis. It can only be performed at laparotomy making it relatively invasive and retreatment impractical. Alcohol is cheap and can be injected percutaneously. However, inhomogeneous distribution produces imprecise and nonreproducible lesions. Low power laser hyperthermia produces precise and reproducible areas of necrosis that are roughly spherical in shape. At present, this technique is most effective for small tumours. Interstitial radiotherapy remains the least evaluated of all the interstitial techniques. Unlike cryotherapy and low power laser hyperthermia, the biological effect of ethanol injection and interstitial radiotherapy cannot be monitored in real time by ultrasound. With the exception of cryotherapy, all methods can be applied percutaneously with low morbidity and mortality. None of these techniques is established, but they may offer the prospect of cure in cases where all areas of tumour can be positively identified and fully treated. However, in most instances the intention is to control the growth of relatively small discrete volumes of tumour within the hepatic parenchyma.

Ten patients with colorectal cancers unsuitable for operation were treated with endoscopic photodynamic therapy (PDT). The patients were assessed before treatment, and at 1 week and 1 month after treatment by colonoscopy with biopsy and endoluminal ultrasound examination. The depth of tumour was measured and the effect of PDT was quantified by measuring the reduction in tumour depth. All patients were sensitized with 2.5 mg kg-1 of haematoporphyrin derivative, 48 h before phototherapy. A standard treatment protocol of light exposure was used. Up to four parts of the tumour were treated with 50J of red light (630 nm) from a tuneable dye laser, through a flexible optical fibre passed through the colonoscope and inserted into the tumour. Two patients with small lesions are tumour-free 20 and 28 months after PDT. One treatment of an advanced tumour was complicated by a haemodynamically significant secondary haemorrhage. PDT may be most suitable for the treatment of small tumours or for small areas of persistent tumour where the bulk has been removed by alternative techniques.

Seventeen patients with cancers of the rectum or distal sigmoid and considered inoperable because of old age, severe concomitant disease or advanced stage of malignancy, were treated endoscopically with the Nd YAG laser. Symptoms included rectal bleeding, obstruction, diarrhoea and incontinence. Significant improvement was achieved in 15 (88 per cent) and there were no complications. The procedure was carried out with simple bowel preparation and minimal sedation and, for otherwise fit individuals, the mean total hospital stay was 6.8 days, with day case therapy sometimes possible. Three patients required further therapy for recurrent symptoms 6-8 weeks after treatment. Fourteen patients died 1-39 weeks after therapy (mean survival 15 weeks). Three are alive and free of bowel symptoms after 39-54 weeks. This technique is the only non-surgical therapy that can be used safely for lesions above the peritoneal reflection and provides palliation at least as good as electrocoagulation, cryotherapy and radiotherapy with minimal upset to these seriously ill patients.

The effects of interstitial delivery of low power (1.2-2 W), long exposure (600-1200 s) Nd YAG laser light on a transplantable fibrosarcoma in rats have been studied. Three cohorts of ten animals were treated either by 1.2 W for 600 s, 1.2 W for 1200 s or 2 W for 600 s to each tumour nodule. An additional untreated cohort served as controls and a further cohort was treated by radical surgical resection. A partial response as evidenced by ulceration was seen in all laser-treated tumours. In the cohort treated by 2 W for 600 s there was complete loss of palpable tumour, and in five out of the ten animals there was no evidence of local recurrence following a prolonged period of observation. Three of these eventually died from metastatic disease and two were cured. There was a significant prolongation of survival in this cohort compared with the controls (median 70 days versus 30 days, P less than 0.05), but not in any of the other cohorts. Histological assessment of tumours 2 days after laser treatment showed a central area of degeneration with shrunken and densely staining nuclei and disorganized cytoplasm, the boundary between the degenerate zone and surrounding viable tumour being well defined. The technique might be used to induce necrosis of intrahepatic and other solid organ tumours.

Palliative treatment of upper gastrointestinal tract obstruction was undertaken by endoscopic laser therapy in 6 patients with carcinoma of the oesophagus or stomach. All had dysphagia for solids on admission and were considered unsuitable for surgery or radiotherapy. Three were in sites unsuitable for placement of an endoscopic prosthesis. The tumours occluded up to 90 per cent of the lumen (2 squamous and 4 adenocarcinomas). Treatment was carried out under direct vision, the laser wave guide being passed through the biopsy channel of a standard endoscope. Superficial tumour vaporized immediately using energies of 2-10 000 J per session, whereas deeper layers sloughed over the succeeding 2-3 days. Two to six treatments were required to relieve dysphagia and there were no major complications. Quantitative barium studies before and after treatment showed a significant increase in luminal diameter. These patients could eat solid food after treatment and all were able to go home.

The application of laser energy to percutaneous recanalization of diseased blood vessels is of interest to vascular surgeons and radiologists. We have examined the effect of pulsed infrared light from a 100 microseconds pulsed Nd-YAG laser on the dog aorta in order to determine the dose response, perforation thresholds and healing properties in vascular tissue. We used 100 microseconds pulses of 0.5 J energy at 10 Hz repetition rate via a 400 micron optical fibre to make 205 craters in 10 dogs at total energies of 5-25 J. The perforation threshold was 15 J in six animals and 20 J in four. The dose response was linear at 10 micron tissue vaporized per Joule delivered. Animals were killed immediately and at intervals of 24 h, 4, 7 and 10 days, 2, 3 and 6 weeks, and 3 and 6 months. Material was retrieved for histology and examined by light and scanning electron microscopy. The tissue exhibited features of laser damage that were less marked than those seen with continuous wave lasers; there was less heat damage surrounding the craters which healed well, even after perforation. This laser is likely to be suitable for human laser angioplasty provided the energy is given in increments of 15 J or less.

The argon laser was used to treat 220 patients with port-wine stains with moderate efficacy and few complications although perfect cosmetic results were rarely achieved. Primary failure of the argon laser to produce permanent blanching graded good or excellent was the most important factor limiting the final cosmetic results whilst severe scarring was rare (less than 2%). In order to improve the efficacy of this treatment, a randomized controlled study of different parameters of laser treatment was undertaken in test patches of port-wine stains in 50 patients. A treatment pattern with contiguous or overlapping laser spots was significantly superior to treatment with spots of 1 or 2 mm separation. Increasing the power level to twice the minimum blanching power did not improve efficacy or significantly increase scarring. A randomized study of selective absorption using a neodymium (Nd) YAG laser showed similar efficacy for the different wavelengths although scarring was greater with the Nd-YAG laser. This study has shown that laser treatment can offer a moderately effective treatment for port-wine stains. For best results spot separation needs to be carefully controlled, whilst wavelength and power level appear to be less important than previously reported.