RU2269341C1 - Method for carrying out combined treatment of rectal cancer cases - Google Patents

Abstract

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.

Description

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

A known method for the treatment of malignant tumors of the rectum [1], which to enhance radiation exposure to cancer cells involves the introduction of a radio modifier (metronidazole) injection directly into the tumor tissue while simultaneous local hyperthermia followed by fractional irradiation of the tumor with a dynamic course in a total dose of 20 Gy.

However, the known method does not provide sufficient radiomodification of tumor tissues located endophytic (along the periphery of the tumor), and thus does not eliminate the risk of implantation and lymphogenous metastasis during surgery. In addition, there is a chance of infection and abscessing of the tumor, which negatively affects the course of surgery and increases the risk of postoperative purulent-septic complications.

There is a method of treating colorectal cancer [2], which provides for bringing a radio modifying mixture (diprofillin, partusisten and dimexide) directly to the tumor in the rectal cavity 0.5-1 hour before the radiation therapy session. Radiation therapy is carried out for 4 weeks by traditional fractionation.

However, this method also does not provide sufficient radiomodification of the tumor. Only layers of tumor cells located exophytic are available in contact with a mixture of pharmaceuticals. And in the presence of gross violations of intestinal patency, contact is possible only with the distal parts of the tumor. Thus, a high probability of implantation and lymphogenous metastasis remains. The increase in the terms of preoperative radiation therapy creates additional technical difficulties during the operation due to developing tissue fibrosis in the area of intervention.

A known method of treating rectal cancer [3], which involves the introduction of a radio modifier (metronidazole) through the mouth 3-3.5 hours before summing up a large fraction of the radiation (in total, in four doses 32-48 g of the drug). Radiation therapy is carried out fractionally for 3 weeks. Large fractions (two 6 Gy every other day) patients receive at the beginning and at the end of the course in combination with taking metronidazole (8-12 g once).

However, this method of introducing a radio modifier does not provide selective accumulation in the tumor tissue, has a low radiomodifying effect. However, the method has pronounced side effects associated with organoleptic properties, the irritating effect of the drug on the mucous membrane of the gastrointestinal tract and neurotoxicity.

The closest but technical solution was chosen as the method of selective intra-arterial infusion of chemotherapy followed by balloonization of the artery directly feeding the malignant tumor [4]. The authors showed that intra-arterial infusion, followed by balloonization of the artery, leads to an increase in the concentration of chemotherapy in the tumor by 20-30 times.

For chemotherapy of pelvic tumors (genitalia, bladder), the procedure begins with Seldinger aortic catheterization. Manipulation is carried out under local anesthesia. Then the catheter is set selectively in the area of the branches of the anterior (visceral) portion of the internal iliac artery (VPA). An endoarterially locally drip is administered chemotherapy. Then carry out the reduction of regional blood flow by installing a balloon catheter in the area of the branches of the VPA. Thus, it was shown that a slowdown in blood flow leads to an increase in the duration of contact of the chemotherapy drug with the tumor tissue, its concentration and, accordingly, the effectiveness of the treatment effect are increased.

However, this method of treatment for malignant tumors did not provide for local endovascular radiomodification of the tumor with occlusion of its blood flow and preoperative remote radiation therapy with a single dose of 10 Gy.

The objective of the invention is to enhance the damaging effect of radiation exposure on radioresistant forms of colorectal cancer before surgery, increasing radiation ablasticity and reducing the risk of dissemination of cancer complexes during surgery.

The task is achieved due to the fact that local radio modification is carried out by endovascular perfusion of 5% metronidazole solution into the tumor tissue through the upper rectal artery in the upper ampullar rectal cancer, the upper rectal and one of the internal iliac arteries in the middle and lower ampullar rectal cancer with occlusion of these vessels non-lysing radiopaque emboli, and a single remote radiation therapy with a dose of 10 Gy is carried out 1 hour after radiomodification, and the operation Establish no more than 24 hours after irradiation.

The method is as follows: the manipulation is carried out using the angiographic complex "PHILIPS BV - 212" (Holland), vascular catheters of the company "COOK" and "CORDIS" are used, emboli are metal spirals with a diameter of 0.3 to 0.6 mm, non-ionic contrast substances (omnipack, ultravist), a radio modifier (electron-acceptor compound) - metronidazole 5% - 100 ml, infusomat.

Manipulation begins with selective catheterization of the inferior mesenteric artery (NBA) through the femoral artery according to Seldinger under local anesthesia. After installing a catheter guide at the mouth of the NBA, lower mesentericography is performed by introducing 5-10 ml of contrast medium. After evaluating the angiogram by a catheter guide, a manipulation catheter is brought to the bifurcation or trifurcation of the superior rectal artery (BPA). Additionally, through the latter, the distal branches of the BPA and the tumor tissue supplied by them contrast. Pathological vascular changes in the tumor zone are assessed: the presence of pathological vessels, tumor infiltration of arteries, avascular zones or hypervascularization, early venous discharge. Through a manipulation catheter into the tumor tissue for 20-30 minutes, a 5% metronidazole solution in an amount of 100 ml is perfused slowly using an infusomat. When the tumor is localized in the lower ampulla of the rectum, one of the internal iliac arteries (VPA) is additionally catheterized from the side of the predominant lesion of the intestinal wall. The procedure is supplemented by combined perfusion of metronidazole in the arterial system of the VPA in half dose (5% - 50 ml). Immediately after the perfusion is completed, regional blood flow is occluded in the BPA system with upper- or middle-ampullary cancer (with lower-ampullary cancer - simultaneously in the pool of one of the VPA) by means of endovascular placement of non-lysing radiopaque emboli - Gianturco-type metal spirals in the above vessels.

Metal spirals are delivered to the occlusion site via a manipulation catheter. For the occlusion of the branches of BPA and VPA, usually 8 to 12 metal emboli are required. The adequacy of occlusion, its level is controlled by the position of the radiopaque emboli and the contrast of the vessels on the monitor screen. Occlusion is stopped in the absence of contrast of the distal branches of BPA (or BPA and VPA at the same time). Research and control over the manipulation is carried out in direct projection. After the endovascular manipulation is completed and the catheter is removed, a pressure bandage is applied to the site of the femoral artery puncture. 1 hour after the REV, the patient is given a remote radiation therapy session with a single dose of 10 Gy on the SL-75 linear accelerator in the 360-degree rotation mode. Subsequently, the patient is operated on no more than 24 hours after irradiation.

A method for the combined treatment of colorectal cancer with preoperative endovascular selective radiomodification of a tumor, occlusion of its local blood flow and subsequent remote radiation exposure with a single dose of 10 Gy has been implemented in clinical practice in 25 patients. There were 17 women, men - 8. The stages of the process - III a - III b. In all cases, the diagnosis is verified (adenocarcinomas of various degrees of differentiation) and confirmed by clinical and instrumental methods, including angiography. All patients underwent X-ray endovascular intervention (REV) with tumor radiomodification (metronidazole) through the superior rectal artery (BPA) and local blood flow occlusion. In 8 cases (with localization of the tumor in the lower ampullar region), an additional REV was also performed through the internal iliac arteries (VPA).

The course of the postoperative period after REV in all patients was normal. No specific complications characteristic of intravascular interventions were noted. All patients 1 hour after REV had a remote single radiation therapy dose of 10 Gy. Surgical treatment was performed within 24 hours after REV and radiation therapy. During the surgical intervention, the phenomena of ischemia from the sigma, rectosigmoid department and rectum were not detected. A decrease in the volume of blood loss by 150-200 ml was noted. Atypical cells in abdominal swabs were detected only in 2 patients after mobilization and removal of the tumor. Atypical cells were not found in the swabs after the final rehabilitation of the abdominal cavity and pelvic cavity. At the same time, a rather pronounced damaging radiation biological effect in the tumor cells was achieved, especially with low-grade formations (grade III).

Example 1

Patient Ch., 53 years old, medical history No. 4060, was admitted to the coloproctology department of the Road Clinical Hospital at st. Krasnoyarsk with a diagnosis of Cancer of the lower ampullar part of the rectum (3 cm) T3M0N0P4 (III stage A) with involvement of the posterior wall of the vagina. Clinical manifestations of the disease - within 6 months. I did not immediately seek medical help. Upon admission notes moderate pain in the anus, an admixture of blood in the feces, a change in the shape of feces (ribbon-like feces). The tumor is located in the lower ampullar part of the rectum along the anteroposterior semicircle 3 cm above the dentate line, up to 4 cm long, occupies no more than 1/2 of the circumference of the intestine, narrows the intestinal lumen to 1/3 of the diameter, is mobile, intimately connected with the back wall of the lower third of the vagina. Inguinal lymph nodes are not palpable. Histological analysis No. 50102-05: low-grade adenocarcinoma. The patient was examined. No data were found for the generalization of the oncological process.

The patient underwent combined treatment. Selective catheterization of the superior rectal artery (BPA) was performed under local anesthesia by puncture of the femoral artery to the right according to Seldinger. On angiograms, enrichment of the peripheral channel of BPA is noted, its branches are recalibrated, erratically twisted. In the thickness of the tumor, the accumulation of contrast medium in the form of a “depot” is noted. Metronidazole 5% - 100 ml was perfused with an infusomat for 20 minutes through a manipulation catheter into the arterial pool of the BPA (to the tumor). After this, regional blood flow was occluded in this basin with 4 emboli - metal spirals of the Gianturco type. Next, selective catheterization of the left internal iliac artery (VPA) was performed. An additional 50 ml of a 5% solution of metronidazole was additionally perfused with an infusomat for 15 minutes through a manipulation catheter into the arterial pool of the VPA on the left (to the tumor). VPA is occluded by 4 emboli - metal spirals distal to the place of discharge of the superior gluteal artery. The catheter is removed. X-ray endovascular intervention is completed by applying a pressure bandage to the area of the puncture of the femoral artery.

1 hour after REV, the patient underwent a session of preoperative single remote radiation therapy at a dose of 10 Gy on a linear accelerator SL-75.

The course of the postendovascular and postradiation periods is smooth. No vascular complications, early general and local radiation reactions were noted.

The patient was radically operated 20 hours after the radiation therapy session. A combined shaving-perineal extirpation of the rectum with resection of the posterior wall of the vagina, reduction of the left parts of the colon into the perineum, formation of a coloplastic reservoir with smooth muscle pulp and perineal colostomy were performed. There were no technical difficulties during the operation. Phenomena of ischemia from the side of sigma, rectosigmoid division and the rectum were not detected. Intraoperative blood loss was 350 ml. Atypical cells in the abdominal and pelvic swabs were not detected at all stages of the operation. Histological examination of the removed preparation (rectum with a tumor and posterior wall of the vagina) in the tumor showed a pronounced radiation biological effect - III degree.

The postoperative period is smooth. Discharged in satisfactory condition. Late general and local radiation reactions were not noted. Examined 12 months after treatment - data for a local recurrence of the oncological process and distant metastasis were not revealed.

The proposed method allows to selectively intraarterially bring a radiomodifier to the tumor, create its “depot” and, in combination with preoperative intensive radiation therapy with a single dose of 10 Gy, enhance the radiation damaging biological effect in the tumor tissue, increase radiation ablasticity, and create obstacles to the dissemination of cancer complexes during surgery.

Information sources

1. Patent SU No. 1540072, A 61 N 5/00, 1987.

2. Patent RU No. 2145217, K 31/10, 31/13, 31/52, 1996.

3. Knysh V.I. Colorectal cancer. - M.: Medicine, 1997, p. 54-55.

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

Claims (1)

A method for the combined treatment of colorectal cancer, including local radiomodification of tumor cells, followed by radiation therapy and radical surgery, characterized in that local radiomodification is carried out by endovascular perfusion of its tissue with 5% metronidazole through the upper rectal artery with upper ampullar rectal cancer, upper rectal and one of the internal iliac arteries in the middle and lower ampullary rectal cancer with occlusion of these vessels by non-lysing rents genocontrastal emboli, moreover, a single remote radiation therapy with a dose of 10 Gy is carried out 1 hour after radiomodification, and the operation is carried out no more than 24 hours after irradiation.