Method for carrying out combined treatment of rectal cancer cases

FIELD: medicine.

SUBSTANCE: method involves administering local tumor cell radiomodification with following radiation therapy and radical surgical operation being applied. The local radiomodification is carried out by applying endovascular tumor tissue perfusion with 5% Metronidasole via superior rectal artery in superoampular rectal cancer cases and via superior rectal artery and one of internal iliac arteries in medial and inferoampular rectal cancer cases with said blood vessel occlusion done using non-lytic radiopaque emboli. Single remote radiation therapy is carried out at a dose of 10 Gy 1 h later after radiomodification being over. Surgical operation is done not later than in 24 h after the irradiation.

EFFECT: increased radiation therapy destruction effectiveness.

 

The invention relates to medicine, namely to oncopathology, and can be used for the combined treatment of malignant tumors of the rectum.

There is a method of treatment of malignant tumors of the rectum [1], which is to enhance radiation effects on cancer cells provides for the introduction of radiomodifying (metronidazole) injection directly into the tumor tissue while conducting local hyperthermia with subsequent fractional irradiation of the tumor dynamic course in a total dose of 20 Gy.

However, the known method does not provide sufficient radiological tissue tumors located endofitno (on the periphery of the tumor), and thus does not eliminate the risk of implant and lymphogenous metastasis during surgery. In addition, there is a possibility of infection, abstsedirovaniya tumor that affects the course of surgery and increases the risk of postoperative septic complications.

There is a method of treatment of rectal cancer [2], which involves summing radiomodification mixture (diprofillina, effects and Dimexidum) directly to the tumor in the cavity of the rectum for 0.5-1 hour prior to radiation treatments. Radiation therapy within 4 weeks of the traditional is authorized by fractionation.

However, this method also does not provide dostatocna radiological tumors. Contact with a mixture of pharmaceuticals available only layers of tumor cells located aktfoto. And if there are gross violations of intestinal permeability contact is only possible with distal departments of the tumor. Thus there is a high probability of implantation and lymphogenic metastasis. The increase in terms of preoperative radiation therapy creates additional technical difficulties during the operation because of developing fibrosis of the tissues in the treatment area.

There is a method of treatment of rectal cancer [3], which provides for the introduction of radiomodifying (metronidazole) through the mouth for 3-3 .5 hours before summing up a large fraction of radiation (total, four 32-48 academic admission g product). Radiation therapy is fractional for 3 weeks. A large fraction (two to 6 Grams a day) patients receive at the beginning and at the end of the course in combination with taking metronidazole (8-12 g once).

However, this way of introducing radiomodifying does not provide its selective accumulation in tumor tissue, has a low radiomodification effect. However, the method has severe side effects associated with organoleptic properties irritant effect of the drug on slit the net membrane of the gastro-intestinal tract and neurotoxicity.

The closest but the technical solution chosen method of selective intra-arterial infusion chemotherapy with subsequent balanitaceae artery, directly feeding a malignant tumor [4]. The authors have shown that intra-arterial infusion with subsequent balanitaceae artery leads to an increase in the concentration of chemical in the tumor 20-30 times.

For chemotherapy of pelvic tumors (of the genitals, bladder) the procedure starts with catheterization of the aorta according to Seldinger. The manipulation is performed under local anesthesia. Then the catheter set selectively in the region of the branches of the anterior (visceral) portions of the internal iliac artery (WPA). Endarterial locally infusions of chemotherapy. Then carry out the reduction of regional blood flow by installing a balloon catheter in the region of the branches of the WPA. Thus, it was shown that the slowing of blood flow leads to increased duration of contact of the chemical with the tissue of the tumor, increasing its concentration and, consequently, the efficiency of therapeutic effects.

However, this method of therapeutic effects on the malignant tumor did not involve the local endovascular radiological tumors with occlusion of its blood flow and preoperative remote radiation therap and a single dose of 10 Gy.

The task of the invention is to enhance the damaging effect of radiation exposure on radioresistant forms of rectal cancer before surgery, increasing beam ablation and reduce the risk of dissemination of cancer complexes during the operation.

The task reach due to the fact that local radiomodifying performed by endovascular perfusion in the tumor tissue 5% solution of metronidazole through the upper rectal artery when verhneamudarya colorectal cancer, upper rectal and from the internal iliac arteries in the medium and nizhneamudarya rectal cancer with occlusion of these vessels nasirudeen radiopaque emboli, and a single external beam irradiation dose of 10 Gy spend 1 hour after radiological, and the operation is carried out not later than 24 hours after irradiation.

The method is as follows: the manipulation is done using angiographic complex "PHILIPS BV - 212" (Holland), use of vascular catheters firm "COOK" and "CORDIS", emboli - metal spiral with a diameter from 0.3 to 0.6 mm, non-ionic contrast medium (omnipaque, Ultravist), radiomodifying (electron-acceptor compound) - metronidazole 5% - 100 ml, the infusion pump.

Manipulation begin with selective catheterization of the inferior mesenteric artery (NBA) through badrena the artery by the Seldinger under local anesthesia. After the catheter was inserted wire in the mouth of the NBA hold the lower mesenterica by injecting 5-10 ml of contrast medium. After evaluating angiograms for catheter-guide to bifurcation or trifurcation upper rectal artery (BPA) fail manipulation of the catheter. Additionally, through the contrast of the distal branches of the ENEMY and krovosnabjaemah their tumor tissue. Assess pathological vascular changes in the area of the tumor: the presence of abnormal blood vessels, tumor infiltration of the arteries, avascular zones or hypervascularization, early venous reset. Through the manipulation of the catheter into the tumor tissue within 20-30 minutes inkjet slowly produce perfusion of 5% solution of metronidazole in the amount of 100 ml using infusion. When a tumor is in nizhneamudarya Department rectum additionally kateteriziruyut one of the internal iliac arteries (WPA) from primary lesions in the bowel wall. The procedure Supplement combined perfusion of metronidazole in the arterial system of the WPA in half dose (5% - 50 ml). Immediately after perfusion produce occlusion of regional blood flow in the system ROTATING with an upper - or srednemolekularna cancer (nizhneamudarya cancer - at the same time and in the pool one of the WPA) via endovascular installation in the above with the courts nasirudin radiopaque emboli - metal spiral type Gianturco.

The metal spiral is delivered to the site of the occlusion through the manipulation catheter. For occlusion of branches of the ENEMY, it usually takes from 8 to 12 metal emboli. The adequacy of occlusion, its level is controlled by the position of the radiopaque emboli and contrast of the vessels on the monitor screen. Occlusion stop in the complete absence of contrast distal branches of the ENEMY (or the ENEMY and WPA at the same time). The study and control over the manipulation is carried out in a direct projection. After therapeutic endovascular manipulation and extraction of the catheter at the site of puncture of the femoral artery impose a pressure bandage. Within 1 hour after the patient REV conduct a remote session of radiotherapy dose of 10 Gy to the linear accelerator SL-75 mode 360 degree rotation. In subsequent patient operate not later than 24 hours after irradiation.

The method of combined treatment of rectal cancer with preoperative endovascular selective radiologicaly tumor occlusion of its local blood flow and subsequent remote radiation exposure to a single dose of 10 Gy implemented in clinical practice in 25 patients. Women were 17 men - 8. Stage of the process - III a - III b. In all cases, the diagnosis is verified (adenocarcinoma various degrees different the programme) and confirmed by clinical and instrumental methods including angiography. All patients produced endovascular intervention (REV) radiologicaly tumors (metronidazole) through the upper rectal artery (BPA) and occlusion of the local blood flow. In 8 cases (tumor localization in nizhneamudarya Department) additional REV conducted through the internal iliac artery (WPA).

The postoperative period after REV all patients was normal. Specific complications characteristic of intravascular interventions that are not marked. All the patients within 1 hour after REV conducted a session remote single radiotherapy dose of 10 Gy. Surgical treatment was performed within 24 hours after REV and radiation therapy. During surgery phenomena ischemia from Sigma, rectosigmoidal Department and the rectum is not revealed. Marked reduction of blood loss in 150-200 ml of Atypical cells in the washings from the abdomen revealed only in 2 patients after mobilization and removal of the tumor. Rinse after the final rehabilitation of the abdominal cavity and pelvic cavity atypical cells were found. While there is a pronounced damaging radiation biological effect in tumor cells, especially in poorly-differentiated lesions (III degree).

Example 1.

Sick Hours, 53, case history No. 406, was admitted to the Department of Coloproctology Road clinical hospital at the station Krasnoyarsk with a diagnosis of Cancer nizhneamudarinskogo division of the rectum (3 cm) T3M0N0P4 (III and stage) with involvement of posterior wall of vagina. Clinical manifestations of the disease within 6 months. Medical help is not immediately addressed. When entering notes moderate pain in the anus, blood in the stool, change in the form of feces (ribbon-like stools). The tumor is located in nizhneamudarya Department of the rectum on the front-left semicircle at 3 cm above the dentate line, with a length of 4 cm, takes no more than 1/2 the circumference of the intestine narrows the lumen of the intestine to 1/3 of the diameter, agile, intimately connected with the rear wall of the lower third of the vagina. Inguinal lymph nodes are not palpable. Histological analysis No. 50102-05: poorly-differentiated adenocarcinoma. The patient examined. Data for the generalization of ecoprocess not found.

Patients received combined treatment. Under local anesthesia produced by selective catheterization of the upper rectal artery (BPA) through a puncture in the femoral artery to the right according to Seldinger. On angiogram marked enrichment of the peripheral channel of the ENEMY, her branch is recalibrated, randomly convoluted. In the thickness of the tumor is observed accumulation of contrast agent in the form of a "depot". the via manipulation of the catheter in the blood pool BPA (tumors) were perfusion metronidazole 5% - 100 ml using infusion for 20 minutes. After that produced by occlusion of regional blood flow in the basin 4 emboli - metal spirals type Gianturco. Next carried out a selective catheterization of the left internal iliac artery (WPA). Through the manipulation of the catheter in the blood pool of the left WPA (tumor) performed in addition perfusion another 50 ml of 5% solution of metronidazole using infusion over 15 minutes. The WPA occluded 4 emboli - metal spirals distal to the site of discharge of the upper gluteal artery. The catheter is removed. Endovascular intervention is completed by the imposition of a pressure bandage on the area of the puncture of the femoral artery.

Within 1 hour after REV sick conducted the session preoperative single remote radiation therapy at a dose of 10 Gy to the linear accelerator SL-75.

For postindustrialnogo and postradiation periods smooth. Any cardiovascular complications, early General and local radiation reaction is not marked.

Sick radical surgery after 20 hours of sessions of radiation therapy. Had combined Bruno-perineal extirpation of the rectum with resection of the posterior wall of the vagina, the reduction of the left departments of the colon in the crotch, forming maloplastichnye tank to smooth the muscle sphincter and perineal colostomy. Technical difficulties during the operation is not marked. Effects of ischemia from Sigma, rectosigmoidal Department and the rectum is not revealed. Intraoperative blood loss was 350 ml of Atypical cells in the washings from the abdomen and pelvic cavity at all stages of an operation is not detected. Histological examination of the removed product (rectum with a tumor and the back wall of the vagina) in the tumor marked by a pronounced radiation biological effect of the third degree.

The postoperative period is smooth. Discharged in a satisfactory condition. The late General and local radiation reaction is not observed. Surveyed 12 months after treatment data for local recurrence of ecoprocess and distant metastasis was not detected.

The proposed method allows selective intraarterially be administered to a tumor of radiomodifying, to create the "depot" in combination with preoperative intensive radiation therapy, a single dose of 10 Gy to strengthen radiation damaging biological effect in tumor tissue, increase radiation ablestik, create obstacles to the dissemination of cancer complexes during the operation.

Sources of information

1. Patent SU # 1540072, And 61 N 5/00, 1987.

2. Patent RU NO. 2145217 TO 31/10, 31/13, 31/52, 1996.

3. Knish V.I. Cancer of the colon and rectum. - M.: Medicine, 1997, p.54-55.

4. Chen H., Gross J. Intra-arterial infusion of anticacer drugs: theoretic aspects of drug delivary and review of responses // Cancer Treat. - 1980. - Vol.64, No. 1. - P.31-40.

The method of combined treatment of rectal cancer, including local radiomodifying of tumor cells with subsequent radiotherapy and radical surgery, characterized in that the local radiomodifying performed by endovascular perfusion its tissue 5%solution of metronidazole through the upper rectal artery when verhneamudarya colorectal cancer, upper rectal and from the internal iliac arteries in the medium and nizhneamudarya rectal cancer with occlusion of these vessels nasirudeen radiopaque emboli, and a single external beam irradiation dose of 10 Gy to carry through 1 h after radiological, and the operation is carried out not later than 24 h after irradiation.



 

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