Method for prediction of duration of recurrence-free interval in patients with rectal cancer

FIELD: medicine.

SUBSTANCE: method for prediction of duration of a recurrence-free interval in patients with rectal cancer consisting in the fact that the surgical removal of a peritumoural recurrence is followed with biochemical analysis of the concentration of polypeptide hormone prolactin, and its specified tissue value enables to determine duration of the recurrence-free interval.

EFFECT: method allows predicting duration of the recurrence-free interval following the removal of the recurrence.

1 tbl

 

The invention relates to medicine, namely to biochemical research in Oncology, and can be used to identify prognostic factors in individual assessment of the timing of the development of relapse in women with cancer of the rectum.

Data of medical statistics show that in recent decades in many countries, including in Russia, there has been a steady increase in the incidence of rectal cancer in the background of the continued mortality from this disease. However for a number of reasons at the primary treatment in the majority of cases (80%) patients diagnosed tumors in advanced stages. Colorectal cancer is characterized by a high frequency of recurrence, and therefore 40-50% of patients die within the first 5 years from processes associated, primarily, with the development of relapse, and with the appearance of distant metastases. This situation determines the necessity of the search for prognostic factors for individual assessment of an increased risk of relapse in cancer patients this localisation planning adequate medical tactics in the process of dynamic monitoring of such patients.

There is a method of forecasting resetstatistics and overall survival of patients with recurrent breast cancer (Lopez-Guerrero lose A.et al. Int. J. Cancer, 2006, v.118, p.1743). The authors investigated the contents of the oncoprotein HER2 tissue recurrence of breast cancer using the Hercep Testa R, and method of fluorescent hybridization. It was found that amplification of this protein in the tissue of tumor recurrence is an adverse prognostic factor is the increase in the concentration of protein was negatively correlated with life expectancy of patients without the development of metastases, as well as with their overall life expectancy. On this basis, the authors propose to use the value of the content of HER2 tissue recurrence of breast cancer as a prognostic factor for possible evaluation resetstatistics and overall survival in women with advanced recurrent breast cancer. The disadvantage of this method is the fact that HER2 protein is detected in the tissue of malignant tumors of the breast, however, there is currently no information about its content in intestinal tumors, and therefore this method of forecasting can not be used in patients with this localization process. In addition, the authors suggest the use of the investigated factor when predicting General and resetstatistics survival, but not as a forecast of development of recurrent disease.

Known prognostic role of system state act is activate your product plasminogen in tumors of patients with gastric cancer (Gerstein Y.S. and others will Accompany therapy on Oncology., 2007, No. 1-2, p.57). The authors found that in cancer of the stomach is increased plasminogen activation by urokinase type (increase Ira) with a parallel increase in the concentration of the inhibitor of plasminogen activator PAI - 1 in the tumor compared with the surrounding mucosa of the stomach. Discovered by the authors of the changes are most pronounced in the later stages of the disease. Analysis of the results of the study allowed the authors to conclude that high concentrations of uPA (more 0.37 ng/mg protein) and PAI - 1 (more to 1.61 ng/mg protein) in tumor tissue of patients with gastric cancer can be regarded as adverse prognostic factor associated with lower overall survival of patients. The disadvantages of this method of prediction can be attributed to the well-known fact of differences in the nature of metabolism in different sections of the gastro-intestinal tract, and therefore the performance characteristic of the pathological process in the stomach, may have a different orientation dynamics and a different relationship with clinical factors in the development process in other departments, in particular in the rectum.

There is a method of assessing the expression of the kinase Aurora-A in centrosome-associated and mt-P53 in colon cancer and their significance in malignant process of this localization (Su Xiao-Lu et al. J. Forth Milit. Med. Univ. 2007, 28, No. 4, p.2263), chosen as protot the PA. The authors have investigated the protein expression of Aurora-A and mt-P53 in the preparations of colon cancer, adjacent to tumor tissue and normal tissue of the colon. When comparing the obtained results with clinical and morphological parameters, it was found that overexpression of Aurora-A and mutation mt-P53 plays a critical role in tumor Genesis and tumor progression of colon cancer. Based on this, the authors propose to use the simultaneous determination of Aurora-A and mt-P53 as factors for early diagnosis of colon cancer and prediction of prognosis of patients with this pathology. The disadvantage of this method can be considered as the development of the proposed indicators for early diagnosis and evaluation of the progression of colon cancer, while in relation to the development of recurrent rectal cancer the significance of these indicators has not been studied.

One of the significant factors in the development of cancer recurrence is the state of the tissue at the site of tumor localization (Frank GA, Grew up. on Oncology. zhurn., 2006, №3, p.50). Depending on the specifics of its metabolic status and differences in the content of bioregulators she can contribute, and, to a certain extent, to prevent the emergence and growth of tumors. The importance of the level of biologically active compounds in ambient the overall fabric is connected, first of all, their ability to influence the rate of cell proliferation and antiproliferative activity. Among the interstitial regulators with similar properties include, in particular, hormones, and therefore the search of informative content values in the surrounding tissue connections that can be associated with particular biological behavior of the tumor, its aggressiveness and frequent recurrence, it is advisable to do by examining the hormonal profile of the tissue adjacent to the pathological focus.

The aim of the invention is the identification of factors predicting the duration of recurrence-free period in patients with rectal cancer.

This goal is achieved by the fact that patients with recurrent rectal cancer, developed through different time intervals after surgical removal of the primary tumor in the tissue of the peritumoral area of relapse determine the content of polypeptide hormone prolactin and its level 360,0-372,0 ng/g tissue ascertain the duration of recurrence-free period of 7.5 to 11 months, and at the level of prolactin 512,0-540,0 ng/g tissue ascertain the duration of recurrence-free period during 36-38 months.

"A method for predicting the duration of recurrence-free period in patients with rectal cancer" runs as follows : the m

Under supervision there were 4 women with recurrent rectal cancer. In tissue samples peritumoral area of relapse, obtained during surgery, was determined by the content of prolactin. The results were compared with one of the clinical parameters describing the individual characteristics of relapse - duration of recurrence-free survival of patients. It is established that patients with duration free from disease period equal to 7.5 and 11 months, the prolactin concentration in the tissue of the peritumoral area was 360,0 and 372,0 ng/g tissue. In contrast, a similar fabric in patients with a longer relapse-free survival was 36, and 38 months was associated with greater saturation of the hormone, the substance of which it was 512,0 and 540,0 ng/g of tissue.

Comparative analysis of the values of the considered laboratory test and clinical factors suggests that the status of prolactin in tissue is one of the most important biochemical parameters affecting the degree of remoteness of relapse from the date of resection of primary rectal cancer. The obtained results allow to consider the level of prolactin in the peritumoral zone malignant pathology in the quality factor of the forecast duration of recurrence-free period in women commissioned by the disease. Patients with low levels of prolactin (up to 372,0 ng/g tissue), in contrast to patients with the content of more than 500,0 ng/g tissue have an increased risk of a more rapid development of relapse, and in the case of removal of already developed recurrence may risk it again. In connection with this contingent of patients requires adequate seal graphics periodicity of the survey during the dynamic monitoring for early therapeutic interventions.

The content of prolactin in the tissue of the peritumoral area and the duration of recurrence-free period in patients with recurrent rectal cancer
No.The content of prolactin (ng/g tissue)The duration of recurrence-free survival
1.360,07.5 months
2.372,011 months
3.512,038 months
4.540,036 months

A specific example of the implementation of the program "Method for predicting the duration of recurrence-free period in patients with rectal cancer".

Patient M., born 1940, history-5341/s, was admitted to the Department of General Oncology, RNII 17.04.09 diagnosed with colon cancer, stage 3, T3N0M0, after - anterior resection of the rectum 28.02.06. in RNII, cancer recurrence in sigarettenautomaat, clinical group 2". Histological analysis No. 851598-601 moderately differentiated adenocarcinoma with invasion of all layers in the adrectal lymph nodes metastases no.

When houses in RNII during 2006-2008 ghosla treatment data for recurrence and metastases are detected. When coming to the clinic, RNII 08.04.09. complained of constipation, occasionally blood in the stool.

If fibrocolonoscopia 12 cm from the anal verge detected recurrence in sigarettenautomaat in the form of infiltration with ulceration. Histological analysis No. 21712-14/9 - adenocarcinoma. The patient was hospitalized at the Department of General Oncology.

Recurrence of rectal cancer has developed in a patient after 38 months after excision of the primary tumor.

After preoperative preparation 24.04.09 the operation - abdomino-perineal extirpation of the rectum with the formation of a single salmostoma. Histological analysis No. 26596-600/9 moderately differentiated adenocarcinoma with invasion of tissue, two adrectal lymph nodes metastases of adenocarcinoma.

From the deleted material highlighted in the peritumoral area, which defined the content of prolactin. Its concentration in the tissue was 512,0 ng/g of tissue.

Thus, the patient, duration of recurrence-free period of 38 months, the content of prolactin in the peritumoral area was at a high level.

The postoperative period was uneventful, with no complications. Sutures were removed on the 12th day. With 08.05.09 on 12.05.09. conducted 1 adjuvant chemotherapy. Total intravenous introduced 5-fluorouracil 2500 mg leucovorin 250 mg

The patient was discharged 14.05.09. in a satisfactory condition for postoperative radiotherapy and continuing adjuvant chemotherapy, the oncologist at the place of residence.

Postoperative diagnosis: colon cancer, stage 3, after anterior resection of the rectum 28.02.06., relapse in sigarettenautomaat, after abdomino-perineal removing the rectum with the formation of a single salmostoma 24.04.09, T3N1M0, clinical group 2.

Patient T., born in 1954, history 14979/x, enrolled in the Department of General Oncology, RNII 29.01.07. diagnosed with colon cancer, stage 3, T3N0M0, after - anterior resection of the rectum 14.06.06 in the city hospital №6 of Rostov-on-don, cancer recurrence in sigarettenautomaat, clinical group 2". Histological analysis No. 5855-57 well-differentiated is adenocarcinoma invasion all layers in adrectal lymph nodes metastases no.

When coming to the clinic, RNII 22.01.07 complained of constipation. If fibrocolonoscopia 11 cm from the anal verge detected recurrence in sigarettenautomaat occupying 1/2 of the circumference of the intestine and stenosing its lumen. Histological analysis No. 915932-37 - adenocarcinoma. The patient was hospitalized at the Department of General Oncology.

Recurrence of rectal cancer has developed in a patient after 7.5 months after excision of the primary tumor.

After preoperative preparation 08.02.07 the operation - abdomino-perineal extirpation of the rectum with the formation of a single salmostoma. Histological analysis No. 921005-019 moderately differentiated adenocarcinoma with invasion of all layers in the first adrectal the lymph node metastasis of adenocarcinoma.

From the deleted material selected peritumoral area, it was determined the content of prolactin. Its concentration in the tissue was 360,0 ng/g of tissue.

Thus, patients with a duration of recurrence-free period of 7.5 months the content of prolactin in the peritumoral area was subdued.

The postoperative period was uneventful, with no complications. Sutures were removed on the 12th day. With 06.03.07 started postoperative radiation therapy.

The patient was discharged 14.03.07 in a satisfactory condition for outpatient prod is Liene postoperative radiotherapy and adjuvant chemotherapy, the oncologist at the place of residence.

Postoperative diagnosis: colon cancer, stage 3, after anterior resection of the rectum 14.06.06., relapse in sigarettenautomaat, after abdomino-perineal removing the rectum with the formation of a single salmostoma 08.02.07, T3N1M0, clinical group 2.

In 09.08. diagnosed with a relapse of the tumor in the pelvis with the formation of perineal fistula developed after 8 months after removal of the first relapse. Conducted chemoradiation therapy without effect. The patient died from the generalization process.

Thus, decreased levels of prolactin in the peritumoral area of the first relapse indicates a high risk of developing as soon as possible after its removal of repeated relapse.

Technical and economic efficiency of the Method for predicting the duration of recurrence-free period in patients with rectal cancer" is that the identified factors predicting the duration of recurrence-free period in patients with rectal cancer. At high prolactin patients have a good prognosis in relation to the duration of recurrence-free period. In contrast, patients with low levels of the hormone are at increased risk of more rapid development of relapse, the more aggressive nature of the disease, and in the case of removal of p is cidia - the risk of resumption. This category of patients requires a consolidated graphics dynamic surveillance for early therapeutic interventions.

A method for predicting the duration of recurrence-free period in patients with rectal cancer, including biochemical, characterized in that after surgical removal of a relapse in his peritumoral area to define the content of polypeptide hormone prolactin and its level 360,0-372,0 ng/g tissue ascertain the duration of recurrence-free period of 7.5 to 11 months, and at the level of prolactin 512,0-540,0 ng/g tissue ascertain the duration of recurrence-free period during 36-38 months.



 

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