Inoperable rectal tumour, no metastases: A radio-chemotherapy with a favourable response surgery B radio-chemotherapy with a non-favourable response chemotherapy Operable rectal tumour, with metastases: radical surgery of the tumour with resection of the hepatic or lung metastasis radio-chemotherapy radio-chemotherapy followed by surgical treatment. Non-operable rectal tumour with metastases: chemotherapy and radiotherapy. We must remember that the rectum is a fix organ, that represents an advantage for the irradiation process.
The preoperative irradiation has the advantage of preventing the excessive irradiation of other cavity organs, as in the case of the postoperative irradiation, when the small bowel loops drop in the pelvis.
This protocol has been established starting from the actual knowledge regarding the genetics of rectal cancer, and also the studies of fundamental and clinical research which analyzed the response cancer and aggressive behaviour the rectal cancer to different treatment methods.
The oncogenesis is determined by the alternation of the cellular cycle, and initiates the appearance of angiogenesis.
Citokines such as the fibroblastic growth factor, the endothelial growth factor, angiogenin and interleukin 8 mediate and are the promoters of angiogenesis. Those are produced by the tumor cells, T lymphocytes and by other stromal cells. Also, the macrophages and the tumor cells produce urokinase plasminogen activatorwhich favours angiogenesis.
The tumour angiogenesis is responsible for the tumour behaviour, lymphatic metastases and the distant metastases.
The genetic studies have shown that mutations in the p53 suppressor gene may determine the cell production of inhibitors of the apoptosis, which make the tumour cells resistant to chemo-radiotherapy. The evaluation of the status of the p53 gene might allow the appreciation of the tumour aggressiveness in case of a partially located lesion, the response to PCT 5FUthe survival after curative resection, and of cancer and aggressive behaviour prognostic 2.
It is a known fact that the tissue response to irradiation depends of: The cellular apoptosis through disruptions at the DNA level and through the production of free oxygen radicals.
The cellular destructions that affect tumour proliferation. The fibrosis and the densification of the rectal wall. The obliterating arteritis through hyalinisation process.
The blockage of the cells which block the apoptosis. The destruction of the micro-angiogenesis network.
Probleme actuale privind aplicarea protocolului de tratament în cancerul de rect
It must be remembered that hypoxia decreases the destruction of the tumour cells. The different response to cancer and aggressive behaviour is conditioned by several factors: The tumour dimensions The cellular phenotype The tumour angiogenesis. The type of the peri-tumour inflammatory infiltrate - the tumours with mixt infiltrate have a better prognosis. The intra-tumour microvascular density the greatest number of vascular lumen without a muscular wall in an objective field 40X.
The response to radio-chemotherapy may be appreciated: Macroscopic: The decrease of the cancer and aggressive behaviour dimensions Conversions to a more inferior stage. The post-radiotherapy regression reaction was quantified by Bazzetti inwho established 5 degrees of regression of cancer and aggressive behaviour rectal tumour after radiotherapy. R5 - the absence of the regression.
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A good response to R2 radiotherapy almost complete regression was achieved in nearly Therefore, we can say that the radiotherapy response was correlated directly with the initial stage cancer and aggressive behaviour the disease, being favourable for patients in stage II of evolution and weak for those in stage III 3. Under these conditions, a very important problem is the identification of the degree of response to radiotherapy of the tumour and also to the metastases potential, as long-term radiotherapy lasts cancer and aggressive behaviour 4 weeks, to which one may add around a minimum of weeks until the moment in which the patient will be operated on, a total of weeks.
Actual problems regarding the implementation of the treatment protocol in rectal cancer
If the tumour has a low potential for the radiotherapy response, but a high potential for metastases, the benefit of radiotherapy will be decreased and the risk of metastasis will increase exponentially, taking into account the fact that radiotherapy is a form of local treatment and does not prevent metastases.
It is to be noticed that the cancer and aggressive behaviour of the genetic studies are inconstant and have not allowed so far the identification of a genetic marker of predisposition of the rectal tumours to radio-chemotherapy.
Another problem that we cancer and aggressive behaviour like to analyze is regarded to the attitude towards the patients with an R1 response in the Bazetti classification.
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In the treatment guide of the Ministry of Health for colorectal carcinoma in stage I TNM TN0M0it is mentioned that, in carefully selected cases which are correctly staged preoperatively, in centres with experience, one might choose local transanal resection, exclusive radiotherapy or a combination between radiotherapy and limited surgery. The post-radiotherapy regression R0 and its follow-up wait-and-see has the advantage that the patients are spared the complications of surgery and there are two studies mentioned Habr-Gama et al.
Nevertheless, we must state the fact that the surgical treatment in rectal cancer may assume the following complications: Abdominal perineal resection: Impair of the sexual activity Decrease of the quality of life Para-stomal hernia. One must remember that the physiologic mechanisms of defecation are the more affected as the resection descends at the level of the rectum, so that in the case of ultralow resections and in those with colo-anal anastomosis, they are cancer and aggressive behaviour disappeared.
Some of these potential complications induce a big discomfort for the patient and produce a degree of invalidity. They may represent reasons for accusation of malpraxis in the case of a patient in which the anatomical specimen does no longer contain tumour tissue after radiotherapy, and which in the postoperative period remains one of the downfalls of the surgery of the rectum.
It is a reason why the studies regarding this cancer and aggressive behaviour approach have continued.
Rolul genei p53 în prevenirea cancerului de sân - Revista Română de Medicina Familiei
Therefore, a study from Maas et al. In batch II - 20 patients who completely responded from another batch had resection.
Only one patient in batch I presented with local relapse after 25 months, being resolved through surgical treatment. After complete information of the patient regarding the protocol and the surgical complications of the abdominal perineal resection and of the low and ultralow rectal resections, the 4 patients without parietal lesions and without identifiable nodes post radiotherapy have opted for clinical follow-up, denying the surgical treatment.
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Five patients were operated on: Four patients with remaining lesions batch II. One patient with lymph nodes at the level of the mesorectum, but without a remaining lesion at the level of the rectal wall batch I.
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The pathology exam: In the patient with increased lymph node noticed on MRI post-RT, a cancerous lesion was confirmed at the level of the lymph node.
In the 4 patients with a remaining lesion an induration of the wall or different degrees of stenosisno tumour cells were identified. The patients were re-biopsied after radiotherapy. The evolution of the non-operated patients after radiotherapy: One patient with liver metastases after one year, treated with radiofrequency ablation and chemotherapy without any relapse or a continuation of evolution 3 years after radiofrequency ablation.
Three patients with favorable outcome with no local recurrence or metastasis to 4, 3 and 2 years of diagnosis after the diagnosis. The evolution of the patients with a cancer and aggressive behaviour response who were operated on: One patient with liver metastases at 1 year postoperatively through radio-ablation and resection plus chemotherapy.
Four patients with a favourable evolution 3 patients: abdominal-perineal resection, 1 patient: a resection plus anastomosis. After correlating the data from our own experience with data from literature, we consider that, in order to apply the non operative treatment strategy wait-and-seethe patient must meet the cancer and aggressive behaviour criteria: 1.
The lack of the lesion at the level of the rectal mucosa post-radiotherapy or small ulcerations with a negative biopsy. The absence of the lesions at the level of the rectal wall and of the increased lymph nodes at the MRI exam, and on the post-radiotherapy rectal ultrasound 6. The absence of the increased lymph node with cancer characteristics in the mesorectum pre-radiotherapy.
Conclusions 1. The radiotherapy response is an obvious factor for the local evolution. Radiotherapy does not influence and may worsen the distant evolution with metastases through the delay of other associated treatment, surgery or chemotherapy.
Rolul genei p53 în prevenirea cancerului de sân
Because, so far, we do not have a biologic, histologic or genetic marker, in order to predict the tumour response of rectal tumors to radio-chemotherapy it is necessary to: Establish an angiogenesis score which correlates with the tumour regression judged by the tumour volume, the depth of the invasion, the incidence of the local and distal metastases.
The role of chemotherapy in this context will have to be reevaluated in correlation with the angiogenesis score taken pre- and postoperatively. The attentive follow-up of the patients with a complete cancer and aggressive behaviour to radiotherapy respects the criteria aforementioned, allows to avoid the surgical treatment and protects from the complications of the low and ultralow anastomoses, and the non-benefit of the abdominal-perineal resection of the rectum.
In order to implement an attitude as such, it is compulsory to respect a treatment protocol for the post-radiotherapy evaluation, such as: Clinical rectal examination. Rectoscopy cancer and aggressive behaviour biopsy in patients with small ulcerations or small scars at the level of the mucosa.
The pelvic MRI exam. The trans-rectal ultrasound must certify the absence of the cancer lesions at the level of the rectal wall and at the level of the lymph nodes. The biology and paraclinical investigations are included in follow-up protocols of the patient with a rectal neoplasm, for 5 years. In the process of the decision making, the patient has an important cancer and aggressive behaviour after the correct communication of the possibility of evolution in the case of the non-surgery, but also of the possible complications of the surgical treatment in the case of medium and inferior rectal tumours, he may opt for the watchful waiting.
Bibliografie 1. Saclarides TJ. New and controversial issues in the management of colorectal diseases. The Surgical Clinics of North America. Grem JL. Intratumoral molecular or genetic markers as cancer and aggressive behaviour of clinical outcome with chemotherapy in colorectal cancer.
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Marincaş, C. Cirimbei, V. Prunoiu, A. Eliescu, R. Buzatu, I. Ştefan, E. Bratucu, D.
Anunță-mă prin e-mail despre comentariile ce urmează.
Muraraşu, L. Puiu, C. Post-radiotherapy regression - a prognostic factor in rectal neoplasm. Chirurgia Nr. Habr-Gama A, et al.
Probleme actuale privind aplicarea protocolului de tratament în cancerul de rect
Complete clinical response after neoadjuvant chemo-radiation for distal rectal cancer. Surg Oncol Clin N Am. Maas M et al.
Wait-and-see policy for clinical complete responders after chemo-radiation for rectal cancer. J Clin Oncol. Marincaş, Cancer and aggressive behaviour. Prunoiu, E. Bratucu, C.
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Ionescu, R. Buzatu, N. Clinical and paraclinical criteria of patient selection for the non-operative treatment in completely responsive rectal cancer after neo-adjuvant radio-chemotherapy. Chirurgia