Joerg-Peter Ritz

Optical properties of adenocarcinoma and squamous cell carcinoma of the gastroesophageal junction

Photodynamic therapy (PDT) is an alternative to radical surgical resection for T1a or nonresectable carcinomas of the gastroesophageal junction. Besides the concentration of the photosensitizer, the light distribution in tissue is responsible for tumor destruction. For this reason, knowledge about the behavior of light in healthy and dysplastic tissue is of great interest for careful irradiation scheduling. The aim of this study is to determine the optical parameters (OP) of healthy and carcinomatous tissue of the gastroesophageal junction in vitro to provide reproducible parameters for optimal dosimetry when applying PDT. A total of 36 tissue samples [adenocarcinoma tissue (n=21), squamous cell tissue (n=15)] are obtained from patients with carcinomas of the gastroesophageal junction. The optical parameters are measured in 10-nm steps using new integrating sphere spectrometers in the PDT-relevant wavelength range of 300 to 1140 nm and evaluated by inverse Monte-Carlo simulation. Additional examinations are done in healthy tissue from the surgical safety margin. In the wavelength range of frequently applied photosensitizers at 330, 630, and 650 nm, the absorption coefficient in tumor tissue (adenocarcinoma 1.22, 0.16, and 0.15 mm(-1); squamous cell carcinoma 1.48, 0.13, and 0.11 mm(-1)) is significantly lower than in healthy tissue (stomach 3.34, 0.26, and 0.20 mm(-1); esophagus 2.47, 0.21, and 0.18 mm(-1)). The scattering coefficient of all tissues decreases continuously with increasing wavelength (adenocarcinoma 22.8, 12.99, and 12.52 mm(-1); squamous cell carcinoma 19.44, 9.35, and 8.98 mm(-1); stomach 20.55, 13.96, and 13.94 mm(-1); esophagus 20.34, 12.56, and 12.22 mm(-1). All tissues show an anisotropy factor between 0.80 and 0.94 over the entire spectrum. The maximum optical penetration depth for all tissues is achieved in the range of 800 to 1100 nm. At the wavelength range of 330, 630, and 650 nm, the optical penetration depth is significantly higher in carcinoma tissue (adenocarcinoma 0.27, 1.54, and 1.66 mm; squamous cell carcinoma 0.23, 1.71, and 1.84 mm) than in healthy tissue (stomach 0.16, 1.10, and 1.26 mm; esophagus 0.17, 1.47, and 1.65 mm; p<0.05). Above 1000 nm, a higher absorption coefficient of tumor tissue results in a lower optical penetration depth than in healthy tissue (p<0.05). The higher absorption and scattering of the tumor tissue in the wavelength range of available photosensitizer is associated with a low optical penetration depth. This necessitates higher energy doses and long application times or repeated applications to effectively treat large tumor volumes. Photosensitizers optimized for larger wavelength range need to be developed to increase the efficacy of PDT.

Experimental study and first clinical results with a cooled applicator system for interstitial laser coagulation (LITT)

Laser-induced interstitial thermotherapy has proven to be an effective method for the treatment of different types of tumors. Until now the attainable coagulation volume was limited by the maximum applicable energy. The limiting factor was the high tissue temperature around the applicator which may have caused applicator damage. Consequently an internally cooled catheter system has been developed in order to reduce the temperature of the applicator surface and to allow for the application of higher laser powers. The optimal treatment parameters for the Nd:YAG laser were determined on the basis of in vitro studies with porcine tissue. Following these experimental studies, 127 patients with liver metastases were treated with the cooled system. The applicator position and the resulting tissue damage were verified using a MRI on-line monitoring system applying a FLASH-2D sequence. The optimal in vivo treatment parameters were found to be 25 watts for an exposure time of 20 minutes, resulting in coagulated volumes of up to 20 cm3. The experimental and clinical results have proven that the combination of a scattering laser applicator with an internally flushed catheter enables a significant increase in the coagulation volume.

Curative in situ ablation of colorectal liver metastases—experimental and clinical implementation

IntroductionIn situ ablation of colorectal liver metastases is frequently assessed for palliative treatment only. The establishment of clinically relevant lesion size and a lack of long-term survival data were regarded as main limitations to using them with curative intention. In contrast to surgical liver resection, whose oncological findings seem to have remained unchanged over the years, the in situ ablation methods have considerably changed technically and clinically in the last few years.ObjectiveThe aim of the paper was to point out experimental and clinical data underlining the impact of in situ ablation for potentially curative treatment of colorectal liver metastases.DiscussionOn the basis of experimental data, the aim of complete local tumor control (R0 ablation) can only be obtained if additional energy is applied after reaching the tumor-adapted maximal coagulation volume. Analogous to the oncological safety margin in surgical resection, we defined this decisive energy difference as the “energy safety margin” for in situ ablation. The energy safety margin is the energy that must be additionally applied after reaching the plateau in the energy/volume curve to achieve complete tumor coagulation. In addition to that, in situ ablation should be combined with temporary interruption of hepatic perfusion whenever possible to prevent intralesional recurrences. In this way, the thermoprotective mechanism of hepatic perfusion can be effectively eliminated. With restrictions, the survival data after ablation in specialized centers is comparable to surgical resection with concomitantly lower morbidity and mortality. Based on recent findings and with the corresponding expertise in the field of ablation and state-of-the-art equipment, ablation is, thus, an alternative to surgical resection. The combined application of surgical resection and ablation is also a suitable method for increasing the R0 rate and thus helps improve the prognosis of treated patients. In summary, it can be said that in situ ablation is a useful expansion of the therapeutic spectrum of liver metastases and can be applied as an alternative to or in combination with surgical resection.

NALP expression in Paneth cells provides a novel track in IBD signaling.

PurposePaneth cells are part of the innate mucosal immunity of the gut with possible regulatory function. This study intends to identify the gene expression pattern of the orthotopic and metaplastic Paneth cells, searching for differences between metaplastic occurrence between Crohns disease and ulcerative colitis.MethodsPaneth cells were collected in RNAse-free conditions via micro dissection. RNA isolation and super amplification was followed by microarray analysis of whole genome expression activity of the orthotopic and metaplastic Paneth cells. Immunohistology of β-catenin and Frizzled-5 receptor was performed.ResultsHistological analysis showed no morphological or secretory change (Frizzled-5 receptor and β-catenin) in orthotopic and metaplastic Paneth cells. Microarray analysis indicated an increased, but not mutant activation of Wnt/β-catenin signaling and firstly showed expression of NALP 1, 7, 8 and 11 in metaplastic Paneth cells.ConclusionsPaneth cells might play a NALP-mediated role in the pathogenesis of IBD.

Bestimmung der optischen Parameter von gesundem Ösophagusgewebe und Ösophaguskarzinomgewebe zur Entwicklung eines Bestrahlungsmodells für die photodynamische Therapie

Introduction: Photodynamic therapy (PDT) is being increasingly applied in the local ablative therapy of premalignant and malignant esophageal lesions. The aim of this study was to ascertain the optical properties (O.P.) of healthy and tumor-altered esophageal tissue for the first time, thereby making reproducible parameters available for dosimetry in PDT. Material and Methods: To determine the O.P., we used a monochromatic light source (300 – 2500 nm) and an Ulbricht monosphere System. Biopsy specimens from patients with esophageal cancer were divided into three groups. Group I: healthy esophageal mucosa (n = 20); group II: adenocarcinoma (n = 20); group III: squamous cell carcinoma (n = 20). Measurements were made in the wavelength range of 400 to 1100 nm. Results: The absorption and scattering coefficient was always higher in the tumor than in healthy tissue. This resulted in a lower optical penetration depth of the laser light in the tumor tissue (p < 0.01). There were penetrations depths of 1 mm in the wavelength range of classic photosensitive substances. Conclusion: The higher absorption and scattering of tumor tissue in the esophagus is associated with a lower optical penetration depth in the wavelength range of classic photosensitive substances. The lower optical penetration depth requires the application of higher energy doses and longer application times to treat effectively large tumor volumes. Desirable would be the development of newer photosensitive substances from a higher optical penetration depth range to increase the effectivity of PDT.

Correlation of intrahepatic light and temperature distribution in laser-induced thermotherapy of liver tumors and liver tissue

For prediction of the effectiveness of laser-induced thermotherapy (LITT) of liver metastases and for the Planning of laser treatment it is indispensable to achieve knowledge about the intrahepatic light and temperature distribution in order to obtain data for an optimally adapted dosimetry. We evaluated the optical properties of normal and tumorous rabbit-liver ex-vivo using a double integrating sphere technique as well as a Monte-Carlo-simulation. These data were correlated with the measurement of the intrahepatic temperature ditrsibution in-vivo during LITT. In our study we were able to show a positive correlation between ex-vivo results of optical properties and in-vivo results in temperature distribution. The absorption coefficient and scattering coefficients were significantly smaller in tumor tissue than in normal liver. This resulted in a higher optical penetration depth of the laser light into the tumor tissue (p<0.01). Temperature measurement near the applicator was lower in tumor tissue, than that distant from the applicator (p<0.01) corresponding to a higher temperature penetration depth. Both, higher optical and thermal penetration depth in the tumorous tissue was correlated with a significant increase in coagulation volume after LITT.