General: Leidse scientists and oncologists emphasize positive effect of TACE, also at RFA, and treatment of liver tumors LITT PDT through promotion of research of Dr. Duijvenhoven and article in Dutch magazine for medicine. Article update 5 August 2011
27 June 2005: source: LUMC4 July 2005: we now have the OPS members full article from Dutch magazine for medicine available, plus address information from authors of this article, see below. Please send us an email indicating your OPS number and we will send you the article digital allow you can use for request for reimbursement may be a possible treatment for bv. Dr. Vogl or Dr. Gorter or elsewhere abroad.
Wednesday 22 June 2005 received his doctorate on the subject: Mrs van Duijvenhoven Local ablative therapies for colorectal liver metastases and the immune system is freely translated: local surgeries in liver tumors and its effect on the immune system. Who reads the following summary of her doctoral research also sees that the courts approach such as Dr. Mrs. van Duiven Vogl and Dr. Solbiati a.o. apply for years a sizable step forward in treating cancer patients with liver tumors. It is also remarkable that Dr. van Duijvenhoven PDT = Photo Dynamic Therapy calls as an alternative for lasering. She describes the results of a trial with 24 patients who were assisted with PDT of their liver tumors. We hope the study results to look for you
More striking still is emphatic that is listed in this summary that the retention of primary tumor tissue for a very sensible thing would be, also immunotherapies because relatively often a spontaneous activation of the immune system against the primary cancer cells arises after an RFA or LITT or PDT treatment. We also know quite a few people who are Trans-Arterial Chemo-Embolization after TACE a followed by a supplementary treatment or RFA or follow with dendritic cell therapy LITT in order to prevent a relapse and that a spontaneous generation of an immunological response try extra boost. Companies should also Oncovax, a proven vaccine against colon cancer, able to play a major role. But we are not doctors or medical experts so please check everything about these opportunities at your doctor-oncologist. Also read our disclaimer. Today appears in the Dutch magazine for medicine a great article about the possibilities of RFA and TACE and LITT including Dr. Vogl and Dr. Solbiati in a positive sense. Once we get this article available we will also publish here, now the first summary of the PhD research of Dr. mevr. F.H. Duijvenhoven, what's really interesting companies. Apparently there is movement in the recognition of treatment methods that for years our neighbouring countries almost by default.
Wednesday 22 June 2005
14.15 hours Mrs. F. H. of Duijvenhoven
Dutch/English title: Local ablative therapies for colorectal liver metastases and the immune system
Promoter (s) Prof. Dr. O.T. Terpstra
Prof. Dr. R.A.E.M. Tax Collector
Brief summary:
Cancer of the colon is one of the most common forms of cancer in Netherlands, with almost 9000 new patients each year. The prognosis of these patients is bad, particularly if the disease is spread. Metastasis to the liver and eventually takes place mainly happens at more than 50% of patients with colon cancer. If the disease remains limited to extended the liver, there is still a chance of cure if the liver metastases can be removed surgically (resection). Unfortunately, the number of metastases or its location in the liver is often a barrier to operation. There are only about 20-30% of patients with liver metastases eligible for this treatment. The other patients in this group may benefit from other local treatments, where the tumor tissue is not trimmed but by heat, cold or radiation is locally destroyed. Some of these therapies is described in this thesis, such as Photodynamic therapy (PDT) and the radio frequency ablation (RFA). One or more needles are stabbed in the tumour, either through the skin back (closed), either during an open abdominal surgery (open). This needle, an electrode spot of the tumor, caused a temperature rise. By these local heat is the tumor left fire, as it were, while the surrounding healthy liver tissue is not damaged. The latter treatment is only since a number of years in many clinics in Netherlands applied, and in Chapter 7 and 8 we have examined the problems which could arise at RFA. First we will discuss in Chapter 7 the possible complications of treatment for metastatic colon cancer RFA. Nearly 100 patients with liver metastases were treated in various hospitals. The results showed that complications occur after slightly more than 20% of the treatments, with half of these specific complications was caused by the RFA treatment.
Except the complications tumor after RFA treatment is also coming back from a problem. In 87 patients with metastatic colon cancer liver metastases treated with RFA we have. Of the total of 199 metastases treated in almost half the cases came after a period of time (on average after more than half a year) tumor tissue back in place of the previous RFA treatment. Patient-related factors such as age and time of action of metastases bleaching does not affect the chance of local tumor growth. The size of the metastasis was of influence: the larger the tumors, how harder to localachieving control through RFA. On harder-to-reach places also tumors in the liver, such as central to the lever near the large liver vessels to treat effectively harder bleaching. More specific application of this therapy seems therefore necessary, and resection of metastases remains the gold standard treatment for liver metastasis.
Another possible future alternative to resection is the PDT. This uses a combination of a chemical substance, the photosensitizer, and light to tumor destruction to come. The photosensitizer is first administered in the armader of the patient and thus into the bloodstream (intravenous administration). The dust accumulates in the body especially in tumor cells, but also goes to other organs and the skin. In itself is the substance is not effective against cancer, but if he is lit with laser light of a certain wavelength photosensitizer is activated. This happens by the insertion of optical fibers illuminate laser through the skin directly into the tumor, forth (closed procedure). Come in this process oxygen molecules called free radicals, unstable, which ultimately lead to destruction of the tumour cells. The results are discussed In Chapter 6 of PDT treatment of 24 patients with Metastases of colon cancer in the liver, which is not eligible for surgical removal. It involved the first clinical study for liver metastases which PDT was applied and therefore the main goal was to determine whether the treatment was technically possible and safe enough for the patient. Both questions be answered in the affirmative could: there was no PDT-related mortality and serious complications were seen in only 2 patients. These complications were damage to healthy liver and pancreatic, caused during laser exposure of the tumor (s). With an even better placement of optical fibers in the tumour tissue adhesive in the fiber and administration of such problems in the future very likely itinerary can be prevented. A less serious but certainly tedious updating of the PDT is the hypersensitivity of the skin for both Sun-as artificial light. This hypersensitivity is particularly in the first week after administration of the photosensitizer, important as these also in the skin much is present. To prevent this. (Note: red PDT with radachlorin would be a much better alternative companies are in this case because this only in tumor tissue accumulates photosensitizer and not in healthy tissue.
If except resection is not possible, also local treatment by RFA can still benefit from some patients through infusion of chemotherapeutics in treatment of the liver (hepatic artery the arteryinfusion, HAI). This treatment is not administered intravenously in the chemotherapeuticum the armader, but sprayed directly into the artery which the liver of blood provides. In this way a much larger proportion of the chemotherapy directly at the location of the tumors in the liver. Additionally, the largely demolished in the liver chemotherapeuticum immediately and are no longer in the bloodstream. So little comes chemotherapeuticum in the body and are the known side effects such as nausea and preventing baldness. This treatment is in a custom shape in the Leiden University Medical Center much applied, with favourable results.
Both are in the RFA, PDT as effective against liver metastases HAI clinic, but they may have a favourable effect on the tumor in addition to this direct yet another positive effect: treatment of metastases with RFA, PDT or HAI to the emergence of a defensive reaction would be against the tumor cells can lead. This would mean that while only the tumors in the liver be treated there is also an immune response directed against the tumor cells in the entire body is caused. That way local treatment of tumor (s) may also be effective against tumor cells on other places in the body. In Chapter 2 we examined whether such a defensive reaction is actually effective against tumors. Got rats in the liver tumor cells injected, which in a few weeks became liver tumors. A control group received no tumor cells in the liver injected. Hereinafter the same tumor cells injected rats got from both groups, but now in a vein in the leg (intravenous administration). These tumor cells so came immediately into the bloodstream, whereby they were transported to the lungs and lung metastasis could become possible. A part of the rats with liver tumors, however, got instead of tumor cells, only water injected. What we saw is that the rats who already below a liver tumor, metastases in the lungs had no developed after the intravenous administration of tumor cells. Control rats without liver tumor metastases contrary, developed very much long. Apparently had the rats with liver tumors by the first administration of tumor cells in the liver is already an immune reaction against the tumor cells, so they developed the tumor cells which later were brought into the bloodstream could effectively disable. Remarkably, however, was the finding that although these clearly rats were able to destroy the tumor cells in the bloodstream, they disable their tumor in the liver could not: the size and weight of their liver tumors was equal to le ...
Why now was the defensive reaction is effective against the tumor cells in the bloodstream but not against the pre-existing liver tumors? A possible explanation for this is the existence of a protective integument of the liver tumors. The tumor cellsnest located in the liver tissue and as they grow in number, they are surrounded by a protective structure, extracellular matrix. This matrix cells of the immune system does not ensure that the tumor cells can come and they therefore cannot disable. However, the cells in the circulatory system do not have such a protective structure and therefore be recognized and attacked by the immune cells.
This theory was the basis of the experiments in chapters 3 and 4. After all, the local destruction of tumors by RFA has (co-), PDT or HAI cause the protective matrix around the tumor is disrupted. This appearance (parts of) destroyed tumor cells available for recognition by immune cells, which can lead to the emergence of an immune response against the tumor cells. At treatment by surgical removal of the metastasis is not of such a mechanism, because the tumor is removed in its entirety and no dead tumor cells are left behind. In our first experiment with local treatment we have equipped with 3 rats liver tumors (Chapter 3). There was one of these three tumors treated with PDT and then was viewed or this treatment of influence was on the other two, untreated, tumors. We also looked at whether additional immune cells were to be found in the liver tissue surrounding these tumors. The results confirmed our earlier test results (Chapter 2), because we saw that although the PDT was very effective, but that there is no local influence was on the other tumors in the liver. Around these tumors we saw no increase in the number of immune cells, after all, the tumors were unrecognizable for the immune system by their protective environment. This test only told us nothing about the immune response against tumor cells, but a subsequent experiment did loose though. In Chapter 4 we describe the results of this trial, which again rats were equipped with liver tumors, two in this case. Of these two tumors one again, this time was also treated with RFA or PDT. It was also a group of rats treated with HAI. The control group consisted of rats which neither liver tumors were treated. A few weeks after treatment got half the rats injected on a third place in liver tumor cells, while the other half of the tumor cells intravenously administered rats got. In this way we could determine whether a defensive reaction occurred.
Now that we had seen in experimental research a good immune response was caused by local treatment. This threw the question whether the same reaction also appeared in patients who were treated with RFA would be, PDT or HAI. Since it is not possible in the research setting of the rats experiment to mimic people, we looked at the presence of certain antibodies in the bloodstream of patients as a measure of the immune reaction (Chapter 5). TheWe went were directed against tumor cell antibodies that various possible components, whereby we examined whether there was a difference in quantity of these antibodies before and after various treatments of liver metastases (RFA, PDT, HAI and resection). This we examined by blood of patients before and after treatment to test for antibodies directed against 6 different types of cultured darmkanker cells. The results showed that especially after there was a clear increase in treatment by HAI antibody production, while there was a decrease to see correctly after resection. Also after RFA, there was an increase to see, while there are no clear after PDT changes took place. These findings partly confirm our theory: If the tumor is not removed, such as with resection, but continues to sit, as with RFA, after treatment and provides that the opportunity for PDT HAI, the immune system to develop a response against the tumor cells.
The results of the various experiments and investigations are discussed together in Chapter 9. This brings us to the conclusion that local treatments such as RFA and PDT are a welcome and necessary addition on the current treatment options for patients with liver metastases. We must note that the success of RFA and PDT partly depends on a correct implementation. There is definitely room for improvement of these techniques and their applicability as possible can be extended. As regards the immune system we see that the local (RFA and PDT) and regional (HAI) treatments can cause a defensive reaction. This offers many opportunities to further improve the outcome of these therapies, for example by strengthening the immune system of patients extra before, during or after treatment. Can also be produced in the future possible vaccines that are made from tumor cells which have been treated with PDT or RFA. With these developments would eventually grow into a fully-fledged local treatments for resection of liver metastases, and alternative more patients can be treated with probabilityhealing.
