RU2240117C1 - Method for treating patients for locally spread carcinoma cases localized in mucous membrane of oral cavity and oral division of the pharynx - Google Patents

Abstract

FIELD: medical engineering.

SUBSTANCE: method involves administering two chemotherapy courses with cys-platine and 5-fluorouracyl being applied. Then, surgical intervention is carried out with bolus 5-fluorouracyl depositing in the primary lesion focus area being done via the corresponding external carotid branch in intraoperative mode before eliminating the lesion focus. 5-fluorouracyl depositing is repeatedly applied to withdrawn tumor bed and plastic repair of the postoperative defect is carried out in single step using two flaps. Mucoperiosteal flap is applied to hard palatine area. Combined artery-bearing cutanomuscular flap including large thoracic muscle is brought under the clavicle.

EFFECT: enhanced effectiveness if treatment; reduced risk of traumatic complications.

6 dwg

Description

The invention relates to medicine, namely to Oncology, and can be used to treat patients with locally advanced forms of cancer of the oral mucosa and oropharynx.

Known methods of treating patients with locally advanced forms of tumors of the oral mucosa and pharynx, including radiation therapy and surgery in various combinations (Paches A.I. - Tumors of the head and neck. - M .: Medicine, 1997, p. 142 -177, 329-340).

However, the method is ineffective and causes a large number of complications.

The closest to the achieved positive result (prototype) is a method of treating patients with locally advanced forms of tumors of the mucous membrane of the oral cavity and oropharynx, which consists in the appointment of chemotherapy by intravenous administration of cisplatin in a dose of 100 mg / m ² on the 1st day of treatment of each course, 5 fluorouracil in a dose 1000 mg / m ² from day 2 to 6 (2 courses), and during the second stage of combined treatment of surgical intervention, followed by radiation therapy at a dose of 40-46 GR. (Kitsmanyuk Z.D. Malignant tumors of the head and neck. - Tomsk, 1998, p. 122-143).

However, the known method is ineffective and there is a high frequency of complications of chemotherapy and the postoperative period.

The authors propose a new effective method of treating patients with locally advanced forms of tumors of the oral mucosa and oropharynx, consisting in phased treatment: chemotherapy, surgical intervention and simultaneous primary surgical rehabilitation followed by radiation therapy.

The positive results of the proposed method are to increase the effectiveness of treatment by increasing the effectiveness of chemotherapy, increasing the flexibility of surgical intervention, reducing the number of postoperative complications and primary functional rehabilitation of patients.

A positive result is achieved by the fact that at the first stage of combined treatment, 2 courses of neoadjuvant intraarterial regional chemotherapy are carried out: cisplatin at a dose of 100 mg / m on 1 day of treatment of each course, 5-fluorouracil in the form of a 6-hour infusion at a dose of 750 mg / m ² s On the 2nd to 6th day of each course, at the second stage of the combined treatment, a simultaneous surgical intervention is performed on the lymphatic drainage pathways and the primary focus, with intraoperative deposition of chemotherapy drugs in the tumor bed, and at the third stage, the simultaneous eraser defect oropharyngeal difficult arterialized musculocutaneous flap or a combination of patches.

The proposed method is as follows.

The treatment is carried out in stages:

Stage I - the patient is given 2 courses of polychemotherapy,

Stage II - simultaneous extended-combined surgical intervention with intraoperative 2-fold deposition of chemotherapy drugs before removal of the primary focus and in the bed of the removed tumor.

Stage III - simultaneous primary surgical rehabilitation by means of plastic tissue defect followed by a course of radiation therapy.

The first stage of polycheotherapy includes the introduction of two drugs:

1) cisplatin in a dose of 100 mg / m ² on the background of hyperhydration on the first day of each course intraarterially, which is introduced through a catheter installed in one case into the superficial temporal artery, in the other through the occipital artery (figure 1);

2) 5-fluorouracil at a dose of 750 mg / m ² , which is administered to the patient on days 2-6 of each course by a long 6-hour intra-arterial infusion.

The infusion is carried out using a dispenser of medicinal substances "Lineomat" (KARL-MARX-STADT).

II stage. After chemotherapy is completed, 2-3 weeks after the relief of adverse reactions, patients undergo an extended-combined surgical intervention on the lymphatic pathways of the neck and on the primary focus. After treatment of the surgical field according to Grossich under local infiltration anesthesia S. Nov. 0.25% - 30 ml perform a tracheostomy without crossing the isthmus of the thyroid gland. After performing a tracheostomy, premedication is performed: atropine, diphenhydramine, relanium and promedol in standard dosages. Next, an induction anesthesia is performed: ketamine, short-acting muscle relaxants. Intubation is performed through a tracheostomy. Basic anesthesia is performed by using a multicomponent balanced anesthesia:

NLA (fentanyl + droperidol), ataralgesia (fentanyl + relanium + droperidol) in standard dosages based on 1 kg of body weight over time. After giving basic anesthesia, surgical intervention is sequentially performed on the lymphatic paths of the neck and the main focus (figure 2). Intraoperatively produce a bolus deposition of drugs in the area of the primary lesion by catheterizing the corresponding branch of the external carotid artery after prior ligation of the external carotid artery, facial vein, pharyngeal veins before removing the primary lesion. 5-fluorouracil is deposited at a dosage of 250 mg / m ² (Fig. 3). Perform tumor resection. Re-produce the deposition of 5-fluorouracil in a dosage of 250 mg / m ² in the bed of the removed tumor (figure 4). The catheter is removed.

Stage III - plastic surgery of the postoperative defect of the oropharyngeal zone with a complex arterialized musculocutaneous flap, including the pectoralis major, sternocleidom or trapezius muscle (depending on the volume of tissue removed). In a number of cases, for plasty of extensive defects (Fig. 5), a combination of arterialized musculocutaneous and mucoperiosteal flap from the hard palate is used), in most cases, the flap with the inclusion of the pectoralis major muscle is carried out in the neck area under the collarbone (Fig. 6), which eliminates the compression of the vascular pedicle of the flap during bending through the clavicle, increases the possibilities and scope of the flap in the form of plastic material by lengthening it and eliminates a cosmetic defect in the form of an additional volume of soft tissues in the region of lucalia and lateral surface of the neck.

3-4 weeks after surgery, patients undergo radiation photon therapy in the postoperative plan. Photon irradiation is performed on a Rocus-M gamma therapeutic unit with an average radiation energy of Co 60 1.4 MEV, a single dose of photon irradiation is 2.0 Gy, the irradiation mode is 5 times a week, and the total dose reaches 40-46 Gy.

Clinical example.

Patient Izvekov V.N., 60 years old, male, has been treated in the Department of Head and Neck Tumors since April 2000, medical history No. 2256. Diagnosis: cancer of the mucous membrane of the oral cavity of the pharynx on the right T4N1M0. G.D.№2459, 04/13/00, squamous keratinizing cancer. The surface area of the patient’s body was 1.7 m ² . Objectively, before the start of treatment, the patient had a ulcerative-infiltrative form of growth of the tumor, occupying the right retromolar region, the anterior palatine arch, the amygdala niche and the palatine tonsil, the posterior palatine arch extending to the right side of the soft palate, to the mucous membrane of the bottom of the oral cavity to the right in the rear third , to the root of the tongue on the right. There was a limitation of mouth opening to 2 cm, which indirectly indicates the spread of the tumor to the inner pterygoid muscle on the right.

04/20/00, the patient underwent catheterization of the external carotid artery on the right by access through the occipital artery on the right.

From 21.04.00 to 27.04.00, a course of intra-arterial regional polychemotherapy was carried out: cisplatin 170 mg on the 1st day simultaneously with hyperhydration (at the rate of 100 mg / m ² ), 5-fluorouracil by prolonged six-hour intraarterial infusion from the second on the sixth day with a total dose of 5.5 g (based on 1000 mg / m ² ). 05/24/00, catheterization of the external carotid artery on the right by access through the superficial temporal artery on the right. From 05.24.00 to 29.05.00, the patient received the 2nd course of polycheotherapy according to a similar program. The total doses of chemotherapy drugs received by the patient during the second course were the same as during the first course.

After polychemotherapy, examination revealed a residual tumor of mixed growth form, occupying the anterior palatine arch, part of the palatine tonsil.

The effect after chemotherapy was more than 50%. During chemotherapy, the patient developed complications such as aphthous stomatitis and alopecia, corresponding to regional blood supply to the scalp in the occipital and superficial temporal arteries.

3 weeks after the end of chemotherapy, side effects were stopped. 06/27/00, the patient underwent surgery in the amount of: tracheostomy, fascial-sheath excision of the neck tissue in full on the right. After performing fascial-sheath excision of the neck tissue on the right, taking into account the tumor location, after preliminary ligation of the external carotid artery above the level of discharge of the upper thyroid artery, ligation and catheterization of the trunk of the lingual artery was performed. The deposition of 5-fluorouracil in a dosage of 250 mg / m ² . In a single unit, electroresection of the retromolar region, anterior palatine arch, palatine tonsil, posterior palatine arch together with the right half of the soft palate, internal pterygoid muscle, 1/2 tongue with root, and the bottom of the oral cavity was performed. At one time, a through resection of the body and branches of the lower jaw from the articular process on the right to 1 premolar of the lower jaw on the left was performed. Re-deposited 5-fluorouracil in a dosage of 250 mg / m ² in the bed of the removed tumor. The catheter is removed. GD: No. 2072/8, July 4, 00, moderately differentiated squamous cell carcinoma, metastasis to one lymph node. The resulting soft tissue defect in the oropharyngeal zone was compensated by a combination of an arterialized musculocutaneous flap with the inclusion of the pectoralis major muscle and the mucoperiosteal flap from the hard palate, the flap with the inclusion of the pectoralis major muscle was inserted into the neck area under the clavicle and under the sternocleidomastoid muscle. The wound healed by primary intention.

07.17. 00, the patient was discharged from the department for a planned break in treatment.

From 9.08.00 to 7.09.00 the patient underwent a course of remote postoperative gamma therapy, a single focal dose was 2 Gy, 5 times a week, total - 40 Gy. Radiomodification was carried out by introducing 5-fluorouracil at a dose of 500 mg iv twice a week. Complications of radiation therapy: catarrhal epithelitis at a dose of 38 Gy.

According to the proposed method, a total of 22 patients were treated (19 men and 3 women), aged 45 to 70 years. All patients had common forms of tumors of IIIb-IV century, with localization in the region of the oral mucosa - 4 patients, in the tongue - 6 patients, the alveolar process of the upper and lower jaw - 2 patients, oropharynx - 10 patients. All patients underwent 2 courses of polychemotherapy according to the proposed scheme. Efficiency was: complete tumor regression was achieved in 33% of cases (7 patients), partial tumor regression was recorded in 56% of cases (12 patients), stabilization was 11% (3 patients).

Progression was not observed in any patient.

Patients underwent 44 courses of polychemotherapy, during which the following complications were noted: nausea / vomiting of I-II degree - 12 courses, leukopenia of I-II degree - 8 courses, stomatitis - 18 courses, allopecia developed in 14 patients.

Thus, the overall effect of the courses of the studied chemotherapy program was 89%, the toxicity was lower than with standard courses of systemic chemotherapy.

At the 2nd stage of combined treatment, all patients underwent surgical treatment in various volumes, including intraoperative deposition of chemotherapy drugs according to the described method.

In all cases, a radical surgical intervention was performed. In 8 (36% of patients), simultaneous defect plasty was performed with complex arterialized musculocutaneous flaps or mucoperiosteal flaps; in 2 cases, a combination of these types of plastics was used (clinical example).

Postoperative complications developed in 3 (13.6%) patients, 1 patient - seam divergence, healing by second intention with the formation of an orostomy, in 2 patients - seam divergence, healing by second intention with the formation of orthoses, which subsequently closed independently and did not require any additional activities.

At the last stage of treatment, all patients received a course of remote gamma therapy in the postoperative SOD 40-46 Gy plan, depending on the prevalence of the TNM process using 5-fluorouracil at a dose of 500 mg twice a week as a radio modifier.

Thus, the method is highly effective and can be used in specialized oncological institutions involved in the complex treatment of patients with tumors of the oral cavity and oral cavity of the pharynx.

Claims (1)

A method of treating patients with locally advanced forms of cancer of the oral mucosa and pharynx, which involves the appointment of polychemotherapy, including regional intraarterial administration of cisplatin at a dose of 100 mg / m ² on the first day of each course and 5-fluorouracil at a dose of 750 mg / m ² with 2 to 6 days of each course and after 3-4 weeks of surgical treatment, followed by a course of radiation therapy, characterized in that the additional 5-fluorouracil is administered intraarterially by a long 6-hour infusion and during op For treatment, a two-fold intraoperative bolus deposition of 5-fluorouracil in the tumor bed is carried out in stages: after lymphodissection by catheterization of the corresponding branch of the external carotid artery after preliminary ligation of the external carotid artery, facial vein, pharyngeal veins before removal of the primary focus and after removal - in the tumor bed and simultaneously carry out primary surgical rehabilitation by plastic surgery of a postoperative defect with a combination of 2 flaps: a mucoperiosteal flap with Verde sky, complicated arterialized musculocutaneous flap with holding the flap with the inclusion of the pectoralis major muscle under the clavicle.

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