Metastasis, the dissemination and growth of neoplastic cells in an organ distinct from that in which they originated, is the most common cause of death in cancer patients. This is particularly true for pancreatic cancers, where most patients are diagnosed with metastatic disease and few show a sustained response to chemotherapy or radiation therapy. Whether the dismal prognosis of patients with pancreatic cancer compared to patients with other types of cancer is a result of late diagnosis or early dissemination of disease to distant organs is not known. Here we rely on data generated by sequencing the genomes of seven pancreatic cancer metastases to evaluate the clonal relationships among primary and metastatic cancers. We find that clonal populations that give rise to distant metastases are represented within the primary carcinoma, but these clones are genetically evolved from the original parental, non-metastatic clone. Thus, genetic heterogeneity of metastases reflects that within the primary carcinoma. A quantitative analysis of the timing of the genetic evolution of pancreatic cancer was performed, indicating at least a decade between the occurrence of the initiating mutation and the birth of the parental, non-metastatic founder cell. At least five more years are required for the acquisition of metastatic ability and patients die an average of two years thereafter. These data provide novel insights into the genetic features underlying pancreatic cancer progression and define a broad time window of opportunity for early detection to prevent deaths from metastatic disease.

SF-010-4 Distant metastasis occurs late during the genetic evolution of pancreatic cancer

Mycophenolate mofetil and its mechanisms of action.

Confocal Imaging–Guided Laser Ablation of Basal Cell Carcinomas: An Ex Vivo Study

BACKGROUND
Photodynamic therapy (PDT) for cancer patients has developed into an important new clinical treatment modality in the past 25 years PDT involves administration of a tumor-localizing photosensitizer or photosensitizer prodrug (5-aminolevulinic acid [ALA], a precursor in the heme biosynthetic pathway) and the subsequent activation of the photosensitizer by light Although several photosensitizers other than ALA-derived protoporphyrin IX (PpIX) have been used in clinical PDT, ALA-based PDT has been the most active area of clinical PDT research during the past 5 years Studies have shown that a higher accumulation of ALA-derived PpIX in rapidly proliferating cells may provide a biologic rationale for clinical use of ALA-based PDT and diagnosis However, no review updating the clinical data has appeared so far

METHODS
A review of recently published data on clinical ALA-based PDT and diagnosis was conducted

RESULTS
Several individual studies in which patients with primary nonmelanoma cutaneous tumors received topical ALA-based PDT have reported promising results, including outstanding cosmetic results However, the modality with present protocols does not, in general, appear to be superior to conventional therapies with respect to initial complete response rates and long term recurrence rates, particularly in the treatment of nodular skin tumors Topical ALA-PDT does have the following advantages over conventional treatments: it is noninvasive; it produces excellent cosmetic results; it is well tolerated by patients; it can be used to treat multiple superficial lesions in short treatment sessions; it can be applied to patients who refuse surgery or have pacemakers and bleeding tendency; it can be used to treat lesions in specific locations, such as the oral mucosa or the genital area; it can be used as a palliative treatment; and it can be applied repeatedly without cumulative toxicity Topical ALA-PDT also has potential as a treatment for nonneoplastic skin diseases Systemic administration of ALA does not seem to be severely toxic, but the advantage of using this approach for PDT of superficial lesions of internal hollow organs is still uncertain The ALA-derived porphyrin fluorescence technique would be useful in the diagnosis of superficial lesions of internal hollow organs

CONCLUSIONS
Promising results of ALA-based clinical PDT and diagnosis have been obtained The modality has advantages over conventional treatments However, some improvements need to be made, such as optimization of parameters of ALA-based PDT and diagnosis; increased tumor selectivity of ALA-derived PpIX; better understanding of light distribution in tissue; improvement of light dosimetry procedure; and development of simpler, cheaper, and more efficient light delivery systems Cancer 1997; 79:2282-308 © 1997 American Cancer Society

5-Aminolevulinic acid-based photodynamic therapy. Clinical research and future challenges.

This article represents a planned regular updating of the previous British Association of Dermatologists guidelines for the management of basal cell carcinoma. These guidelines present evidence-based guidance for treatment, with identification of the strength of evidence available at the time of preparation of the guidelines, and a brief overview of epidemiological aspects, diagnosis and investigation.

https://www.bad.org.uk/library-media/documents/BCC_2008.pdf

Guidelines for the management of basal cell carcinoma

Epidermal damage and limited coagulation depth with the flashlamp-pumped pulsed dye laser: a histochemical study.

Background and Objective

Er:YAG lasers are known to superficially ablate skin and other tissues with minimal thermal coagulation zones. The ablation efficacy and thus the clinical applicability of these lasers, however, was limited due to small beam diameters and repetition rates. Aim of this study was to determine the ablation efficacy and the amount of thermal damage with a new high-power high-repetition-rate Er:YAG laser and to find optimal treatment parameters for skin ablation.



Study Design/Materials and Methods: In vitro and some in vivo ablation trials on human skin were performed with the Er: YAG laser (MCL 29, Aesculap-Meditec, Heroldsberg, Germany, 2.94 μm., max. 500 mJ per pulse, 250 μs pulse length, 3 or 4 mm spot size, repetition rate 7–10 Hz) and evaluated microscopically.



Results

The ablation threshold was around 1.6 J/cm2. The ablation rates increased linearly with the fluence, and the above-threshold ablation efficacy was around 2.5 μm per pulse per J/cm2, leading to ablation velocities of 70–100 μm per second and higher. With increasing pulse numbers applied to one tissue spot, the ablation per pulse decreased significantly. The amount of thermal damage was clearly dependent on the number of pulses applied (around 25 μm with < 10 imp., up to 100 μm with 40 imp.), whereas higher fluences increased the coagulation zones only minimally. The in vivo trials confirmed these results: overlapping pulses in the 4 J/cm2-range, applied in a sweeping motion, proved optimal for an efficient skin ablation with a smooth resulting surface and a thermal damage zone not exceeding 50 μm.



Conclusions

The high power and the high repetition frequency make this laser a fast and effective tool for skin ablation without increasing the thermal damage, but the ablation remains limited to the superficial dermis, since hemostasis cannot be achieved due to the absence of coagulation. Lasers Surg. Medicine 20:242–247, 1997. © 1997 Wiley-Liss, Inc.

Fast and effective skin ablation with an Er:YAG laser: Determination of ablation rates and thermal damage zones

Background and Objective
The aim was to investigate the efficacy, side effects, and the long-term results of a long pulsed Nd:YAG-Laser for hair removal in different hair colors and skin types.

Study Design/Materials and Methods
We performed a prospective clinical study with 29 volunteers. Treatment was performed on the lower leg with a long pulsed Nd:YAG-Laser. Five test areas were treated 1–5 times in monthly intervals; one served as control. Follow-up investigations were performed at each session, and 3, 6, and 12 months after the last therapy. No depilatory treatment except shaving was allowed during the time of follow-up. Percentual hair loss, short- and long-term side effects, and pain during the treatment were evaluated.

Results
After one month, a hair loss of greater than 50% was found in 44.9% of the areas treated once. With up to five treatments, this percentage increased up to 71.5%. One year after therapy, a greater than 50% hair reduction was still present in 40% of the five-treatment-areas and in 0% of the areas treated only once. There were no permanent side effects despite one small scar after a folliculitis.

Conclusions
The long pulsed Nd:YAG is suitable to remove hair for more than 12 months effectively, although 4–5 sessions are necessary for these results. Blond hair can also be removed, although much less effective. No lasting side effects could be seen. Darker skin types or tanned skin can also be treated without side effects. A cooling may be advisable due to the pain reported by the volunteers. Lasers Surg. Med. 30:127–134, 2002. © 2002 Wiley-Liss, Inc.

Hair removal with the long pulsed Nd:YAG laser: A prospective study with one year follow‐up

Background and Objective

In the Western world, there are at least 20–30 million people with tattoos. Improved self-image and social stigmatization are the main reasons for removing tattoos from skin. Q-switched lasers are applied to destroy the tattoo compounds in the skin. The treatment of tattoos containing ink often gives excellent results, whereas the results of treatments for coloured tattoos are not predictable and usually are worse. The chemical structure and the absorption spectra of the tattoo pigments are usually unknown. However, the efficacy of the treatment by using light of different Q-switched lasers (wavelengths 510, 532, 694, 755, 1064 nm) is correlated to both the chemical structure of the tattooed compounds yielding specific absorption spectra and the laser wavelength used.



Study Design/Materials and Methods

A structural and spectroscopic analysis of 41 coloured pigments was performed.



Results

The 41 substances were identified, and they consist of 16 individual chemicals of different structured well-known industrial organic pigments. The absorption spectra of the 16 pigments were measured quantitatively.



Conclusion

The results of the present analysis explain to some extent the outcome of clinical studies regarding laser therapy of coloured tattoos. Because the laser energy used produces a high temperature in the azo or polycyclic pigments, it is necessary to investigate whether that change causes possibly toxic or cancerogenic compounds. Lasers Surg. Med. 26:13–21, 2000. © 2000 Wiley-Liss, Inc.

Q-switch laser and tattoo pigments: first results of the chemical and photophysical analysis of 41 compounds.

Background and Objective

Continuous wave lasers or incoherent lamps are used effectively for photodynamic therapy (PDT). As the mechanism of action of pulsed lasers in PDT is not known, we investigated the efficacy of PDT with 5-aminolevulinic acid (ALA) using a long-pulse (1.5 ms) tunable flashlamp-pumped pulsed dye laser (LPDL) in vitro and in vivo.



Study Design/Materials and Methods

HaCaT human keratinocytes were incubated with ALA (3 mmol/l) and irradiated (0–50 J/cm2) using the LPDL at 585 nm, 595 nm, or 600 nm vs. an incoherent light source (580–740 nm). Topical ALA-PDT was performed on 24 patients with actinic keratoses (AK) on the head (n = 200) after incubation with a 20% ALA emulsion and irradiation by either an incoherent light source (160 mW/cm2, 60–160 J/cm2) or the LPDL (585 nm, 18 J/cm2).



Results

Maximal cytotoxic effects in vitro were achieved using the LPDL at 585 nm or the incoherent lamp (50 J/cm2). Sodium azide, a quencher of singlet oxygen, significantly reduced cell killing, suggesting that the cytotoxic effects are mainly mediated by singlet oxygen. This is supported by an increase of lipid peroxides as determined by malondialdehyde after adding D2O. Complete remission was achieved in 79% of 100 AK treated by ALA and the LPDL and in 84% of 100 AK treated by ALA and the incoherent lamp. Pain during light treatment was significantly reduced by using the LPDL. Control lesions (LPDL without ALA) did not clear.



Conclusion

These results show the in vitro and in vivo efficacy of ALA-PDT using a pulsed light source mediated by singlet oxygen. Lasers Surg. Med. 25:51–59, 1999. © 1999 Wiley-Liss, Inc.

Ulrich Hohenleutner

Papers

Epidermal damage and limited coagulation depth with the flashlamp-pumped pulsed dye laser: a histochemical study.

Fast and effective skin ablation with an Er:YAG laser: Determination of ablation rates and thermal damage zones

Hair removal with the long pulsed Nd:YAG laser: A prospective study with one year follow‐up

Q-switch laser and tattoo pigments: first results of the chemical and photophysical analysis of 41 compounds.

Long-pulse dye laser for photodynamic therapy: Investigations in vitro and in vivo