RU2585431C1 - Method for combination therapy of benign prostatic hyperplasia of large dimensions in aged patients or patients with marked intercurrent pathology - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to medicine, specifically to urology. Transurethral prostate resection is performed with creation of a channel at 12 hours and subsequent expansion thereof for 11 to 1 hour. Before operation, patient is administered 0.5 mg × dutasteride once a day for three months. Method includes performing bipolar transurethral prostate resection in physiologic saline to form channel in effectively loop bipolar loop, starting from bladder neck on 12 hours of conditional clock with depth of up to 3 mm, with expansion from 11 to 1 hour. Channel is completed by resection of side lobes of prostate on 5 and 7 hours with thickness of up to 5 mm from bladder neck to seed tubercle. In postoperative period method includes continuing administration of 0.5 mg × dutasteride to patient once a day until prostate volume is not more than 40 cubic centimetres.

EFFECT: method allows considerably reducing number of complications of surgical management, recovering independent urination or considerably improved, higher quality of life in said patients.

1 cl, 2 ex

Description

The invention relates to medicine, in particular to urology, and can be used to treat patients with benign prostatic hyperplasia (BPH) of large sizes (more than 60 cm3).

Benign prostatic hyperplasia (BPH) is a progressive condition characterized by an increase in the prostate gland (pancreas), accompanied by symptoms of the lower urinary tract (LUTS). Approximately 75% of men over 50 have symptoms resulting from BPH, and 20-30% of patients will need surgery for BPH (Roehrborn CG. Male lower urinary tract symptoms (LUTS) and benign prostatic hyperplasia (BPH) during their lifetime. Med Clin North Am., 2011, Jan; 95 (1): 87-100; Kuzmenko BB, Kochetov MB, Semenov BV Benign prostatic hyperplasia. - Voronezh. - 2008).

Progression of BPH is manifested in increased urination disorders, deterioration in the quality of life (QOL), increased risk of acute urinary retention (OZM) and the need for surgical intervention (Loran O. B., Lukyanov I.V. Practical urology: what's new in the treatment of BPH - expert opinion Russian Medical Journal. 2008. No. 29. S. 1988).

The goal of the treatment of BPH is to improve the patient’s QOL, reduce the severity of LUTS and prevent the development of complications.

Surgical intervention is indicated if: there is no effect of drug treatment; the patient does not want to receive drug therapy and insists on a more aggressive treatment; there are strict indications for surgery - not resolving urinary retention, chronic renal failure due to BPH, bladder stones, persistent urinary infection, repeated episodes of hematuria, refractory to therapy with 5a-reductase inhibitors. An important factor is allergy or contraindications to the use of appropriate medications, as well as the desire of the patient himself, who chooses in favor of a faster and riskier achievement of the result (Höfher K. et al, 2007; Matthew A et al, 2011).

Transurethral resection (TUR) of the pancreas still remains the universally recognized “gold standard” for surgical treatment for BPH and associated LUTS (Rassweiler J et al, 2006). According to the European Association of Urology (2006), TUR pancreas currently accounts for up to 95% of all operations performed in patients with BPH. According to K. Höfher et al (2007), about 60,000 people are operated on annually in Germany for BPH. Having high clinical efficacy, TUR pancreas has a number of complications that are detected in 11-19% of operated patients (Tkachuk I.N., 2011). These complications are divided into intraoperative, early and late postoperative (Rassweiler J et al, 2006; Abrams Ρ et al, 2009; Hahn R. et al, 2007; Kevin T. et al, 2010; Collins M., Kim E, 2011) . According to Sergienko N.F. et al., 2010, the total number of immediate postoperative complications (14.5%) and complications in the long term (16.7%) after pancreatic TUR was 31.2%. A significant number of authors note that in 10-20% of operated patients, during and after monopolar TURP, severe complications and life-threatening conditions are observed, which limits the use of this method, especially in somatically burdened patients (Mosoyan M.S., 2004; Koroteev M .A., 2010; Kamalov A.A., Sevryukov F.A., 2012).

Currently, to eliminate the shortcomings of monopolar TUR, a method of transurethral endoscopic treatment of BPH with a bipolar arrangement of electrodes in a resectoscope has been developed - bipolar TUR of the pancreas (Petrov, S.B., 1998; Popov, S.V. et al., 2010; Beiko DT et al, 2008; Singh H et al., 2008; G. Wendt-Nordahl et al., 2005; Shellock, FG, 2003; M. Alschibaja F. et al., 2005). This method has advantages over the monopolar method in that it eliminates the risk of unintentional tissue burns, reduces the volume of surgical trauma [Lai J., et al. 2004; Kirillov S.Α. 2004.]. In addition, saline solution used in the bipolar technique as a washing liquid helps to increase safety. The advantages of this method over monopolar TUR are also a reduced risk of massive bleeding during surgery, TUR syndrome, hyponatremia; reduction of the risk of infection and sclerosis of the urinary tract in the postoperative period due to a reduction in the timing of the placement of the urethral catheter; good tolerance in patients with severe cardiovascular disease and in the presence of a pacemaker [Yael W. 2004; Egote A.K. 2006. Kirillov S.Α., 2004; Yoo T.K. et al, 2004; Beiko D.T. et al., 2008; Hausner, C.Y., 2003; Monga, M., 2002; Patel, Α., 2003; Berger AP et al., 2004; European Association of Urology Guidelines, 2014).

Drug treatment for BPH according to EAU recommendations includes the use of drugs from the groups of 5 α-reductase inhibitors and α-blockers (Oelke M. et al. Guidelines on Management of Male Lower Urinary Tract Symptoms, 2013).

Inhibitor 5 of α-reductase dutasteride reduces the degree of intraoperative bleeding when performing bipolar TUR in patients with a large prostate volume (≥50 ml) if taken within 8 weeks due to a decrease in prostate vascularization (Pushkar D.Yu. et al., 2010; Busetto GM et al., 2014).

There is a group of patients with a large prostate (more than 60 cm3) who have a high degree of anesthetic risk - these are patients with BPH of old age (over 75 years old) or earlier, but with a pronounced intercurrent pathology. Treatment of patients in these groups is relevant, since according to many researchers there are a lot of such patients. There is an extensive group of patients who are younger than 75 years old, but have severe concomitant pathology that interferes with surgical treatment. Many of these patients have obstructive urination, and a significant proportion have cystostomy drainage. These patients are usually denied surgical treatment due to the high risk of blood loss, duration of surgery, prolonged postoperative drainage of the bladder, significant intra- and postoperative mortality, and also due to decompensation of body systems and organs.

At the same time, long-term conservative therapy in these patients in most cases is ineffective due to severe urination disorders, large volumes of the prostate.

Thus, it is relevant to search for further ways to improve the treatment of large-scale BPH (more than 60 cm3) in senile patients or with severe intercurrent pathology.

A known method for determining the type of treatment of patients with benign prostatic hyperplasia according to the patent of the Russian Federation No. 2205001 (05.27.2003), which consists in performing uroflowmetry, characterized in that repeated uroflowmetry is performed 2 weeks after taking 1-blocker, for example tamsulosin, and in case of improvement urodynamic indicators continue drug therapy, and in case of deterioration, surgical treatment is prescribed. The disadvantages of the method are: low efficiency of the method of uroflowmetry, the possibility of a sharp decrease in blood pressure in the patient. In addition, 1 α-blocker affects only smooth muscle receptors, that is, on irritative symptoms.

A method for the treatment of BPH by prescribing dutasteride is described, in which the minimum term for prescribing dutasteride is 6 months (Kogan M.I. Clinical analysis of the case of benign prostatic hyperplasia. Breast cancer. Volume 19, No. 16 (410), 2011). According to the author, the criterion for the effectiveness of the drug is TRUS data, which is performed initially before therapy and after 6 months. treatment.

The disadvantage of this method is the low effectiveness of treatment in groups of patients of senile age or with a pronounced intercurrent pathology.

The prototype of the invention selected a method of treating BPH (Fichtner I., Macedo Α., Voer M., Yoshioka M., Hohenfellner R. Minimally invasive transurethral resection of the prostate gland // Operative urology. Classics and innovations: Guide for doctors / L.G. Managadze N.A. Lopatkin, O.B. Laurent, D.Yu. Pushkar, S.P. Darenkov, N.L. Turmanidze, R. Hohenfellner. - M .: Medicine, 2003. - C. 262-263) . The authors modified the original technique of TURP of the pancreas according to Nesbit, developing a minimally invasive monopolar TUR of the pancreas, which consists in creating a channel by resection of the pancreas for 12 hours and then expanding it from 11 to 1 hour without removing the middle and lateral lobes of the gland under epidural anesthesia. The authors performed surgery in 35 patients for whom the implementation of a standard TUR of the pancreas was impossible due to the high anesthetic and surgical risk.

The disadvantage of the prototype method is the high risk of relapse, the use of this method only with a small amount of pancreas, the use of a monopolar electrode, which increases the risk of complications.

These disadvantages are eliminated in the claimed invention.

The objective of the present invention is to normalize the function of urination in large-scale BPH (more than 60 cm3) in senile patients or in patients with severe intercurrent pathology.

The task involves combined treatment - a preoperative three-month course of therapy with dutasteride in a dosage of 0.5 mg once a day and the subsequent implementation of bipolar transurethral resection of the prostate in saline. During the operation, a channel in the prostate is transurethrally formed by a loop of a bipolar resectoscope, starting from the neck of the bladder, for 12 hours of a conventional dial with a depth of up to 3 mm, with its subsequent expansion in the range from 11 to 1 hour, the channel is formed by resection of the lateral lobes of the pancreas by 5 and 7 hours with a thickness of up to 5 mm from the neck of the bladder to the seed tubercle. Assign postoperative dutasteride 0.5 mg 1 time per day until the prostate volume reaches not more than 40 cm3.

The technical result obtained from the application of the proposed method consists in the fact that it allows to reduce the number of complications from surgical aid, to restore self-urination or to significantly improve it in men of old age or with severe incurrent pathology, to improve the quality of life of these patients.

Preoperative three-month preparation with dutasteride provides through the suppression of the activity of 5-α-reductase isozymes of type 1 and 2 atrophic changes in the glandular and stromal components of pancreatic tissue. Atrophy of the tissue leads to a decrease in the volume of the pancreas and directly the hyperplasia itself, as well as a significant decrease in its vascularization. Subsequently, bipolar transurethral resection of the pancreas in physiological saline is performed with the formation of a transurethral tunnel in the pancreas during surgery by a loop of a bipolar resectoscope. Bipolar TURP (V-TURP) does not have the main disadvantage of monopolar TURP (M-TURP), because allows you to perform surgery using saline (NaCl 0.9%). Unlike M-TURP systems in B-TURP systems, energy does not pass through the patient’s body to reach the skin electrode. The bipolar circuit is closed at the resection site between the active and passive electrode associated with one mount on the resectoscope. B-TURP is preferable due to a more favorable perioperative safety profile - elimination of TUR-syndrome; less bleeding, i.e. less coagulation delay and frequency of blood transfusion; shorter duration of infusion, catheterization, and possibly hospitalization time (Recommendations of the European Association of Urology (EAU), http://medsovet.pro/archiv/2014/No_19_2014/MS_19_2014_01.pdf).

Creation of a canal by resection of the prostate gland for 12 hours of a conventional dial with a depth of up to 3 mm, followed by its expansion in the range from 11 to 1 hour, completion of the canal formation by resection of the lateral pancreatic lobes for 5 and 7 hours with a thickness of up to 5 mm from the bladder neck to the seminal a tubercle in physiological saline is performed in a short time (7-10 min), almost bloodless, because while taking dutasteride, the vascularization of the pancreas is significantly reduced.

Subsequent postoperative dutasteride administration provides a further reduction in the volume of hyperplasia to clinically insignificant sizes (not more than 40 cubic cm).

The inventive method of combined treatment of BPH with large sizes of pancreas (more than 60 cm3) provides an improvement in the quality of life, relieves patients of constant cystostomy drainage, has practically no complications and is possible in patients of senile age (over 75 years old) or in patients with severe incurrent pathology.

Detailed description of the method and examples of its clinical performance

The method is as follows.

For this method, patients with large BPH (more than 60 cm3) are selected with cystostomy drainage / severe obstructive urination, over 75 years old or with severe incurrent pathology, which did not seem possible to carry out standard surgical treatment and have a weak response to inhibitor therapy 5 α-reductase.

According to the indications, patients are prescribed preoperative conservative therapy - dutasteride in a dosage of 0.5 mg once a day for 3 months. Three months later, during a follow-up examination, a decrease in prostate vascularization is established when performing TRZ with pancreatic dopplerography.

Before the start of drug therapy, patients are examined in a standard volume (recommendations of a meeting of the Council of Experts on the treatment of prostate adenoma, Moscow, 2009) - filling out the IPSS-QO1 international scale of prostatic symptoms, performing uroflowmetry, determining the amount of residual urine by ultrasound, determining the volume of the pancreas using TRUS , determination of total blood PSA. Record the received data.

Bipolar transurethral resection of the pancreas is performed in physiological saline (NaCl 0.9%) under subarachnoid anesthesia, which has minimal systemic effect on the patient’s body. For surgical treatment, a 24 Ch bipolar resectoscope from Storz and a high-frequency electrosurgical unit - ERBE VIO 300 B in standard bipolar modes - bipolar cut ++ and bipolar soft coag +, in the form of an unmodulated sinusoidal alternating voltage with a nominal frequency of 350 kHz are used. Transurethrally perform the formation of the channel in the pancreas with a loop of a bipolar resectoscope, starting from the neck of the bladder, for 12 hours of the conventional dial with a depth of 3 mm, followed by its expansion in the range from 11 to 1 hour, complete the channel formation by resection of the lateral lobes of the pancreas for 5 and 7 hours up to 5 mm thick, from the neck of the bladder to the seed tubercle.

In the postoperative period, the patient continues to take dutasteride 0.5 mg 1 time per day until the volume of the pancreas reaches not more than 40 cm3, after which the drug is canceled.

The efficiency of the method is confirmed by the following clinical examples:

Example 1

Patient Eev, 87 years old, was admitted to the department in June 2014. He complained of cystostomy drainage and pain in his area. In January 2014, a cystostomy was imposed on the patient for an OZM. A history of IHD, atrial fibrillation, post-infarction cardiosclerosis (heart attacks in 1997, 2005, 2009), hypertension 3 tbsp. During the examination: a general urine test - leukocyturia, a general blood test is normal; PSA level 2.6 ng / ml. The patient underwent TRUS of the prostate, according to which the volume of the prostate was 79 cm3. The patient was prescribed dutasteride 0.5 mg × 1 time per day. A control prostate TRUS performed after 3 months showed a decrease in blood flow in the paraurethral and paracapsular pancreatic arteries by 15% with a slight decrease in organ volume (72 cm3). Considering the patient’s desire to restore self-urination and the high risk of standard surgical intervention, the patient underwent bipolar transurethral resection of the pancreas in physiological saline according to the claimed method using subarachnoid anesthesia. The duration of the operative benefit is 7 minutes, there was no blood loss. The cystostomy was removed intraoperatively. Urethral catheter removed after 24 hours.

In the postoperative period, the patient continued to take dutasteride 0.5 mg 1 time per day. Follow-up examination after 3 months: a general urine test and a general blood test are normal; PSA level 1.6 ng / ml; residual urine of 40 ml; uroflowmetry: Q max 17.3 ml / s, Q average 10.5 ml / s. Questioning by IPSS - 10 points, QOL associated with urination Qol = 2 points (satisfactory). The patient underwent TRUS of the prostate, according to which the volume of the prostate was 61 cm3. The course of dutasteride therapy was continued. Follow-up examination after 6 months: performed TRUS of the prostate, according to which the volume of the prostate was 39 cm3. Dutasteride has been canceled.

Example 2

Patient Sh-ev, 68 years old, was admitted to the department in March 2014. He complained of sharply difficult urination, a feeling of incomplete emptying of the bladder. Sick for 2 years. During the year, it takes adrenergic blockers without a pronounced effect. A history of ischemic heart disease, supraventricular extrasystole, polytopic supraventricular tachycardia, discirculatory encephalopathy II tbsp. atherosclerotic genesis, with discoordinate syndrome, peripheral cancer with centralization of the lower lobe of the left lung T2NxM0. During the examination: a general urine test and a general blood test are normal; PSA - 4.2 ng / ml; residual urine volume of 150 ml; uroflowmetry: Q max 11.0 ml / s, Q average 5.7 ml / s. Questioning on IPSS - 25 points, QOL associated with urination, Qol = 6 points (horrible). The patient underwent TRUS of the prostate, according to which the volume of the prostate was 96 cm3. The patient was prescribed dutasteride 0.5 mg / 1 time per day for 3 months. A control prostate TRUS performed after 3 months showed a decrease in blood flow in the paraurethral and paracapsular prostate arteries by 12% with a pancreatic volume of 85 cm3. Given the patient's desire to normalize urination and a high risk of standard surgical intervention, the patient underwent bipolar transurethral resection of the pancreas in physiological saline according to the claimed method using subarachnoid anesthesia. The duration of the operating allowance is 8 minutes, there was no blood loss. Urethral catheter removed after 24 hours. After the operation, the patient continued to take dutasteride 0.5 mg 1 time per day.

Follow-up examination after 3 months: a general urine test and a general blood test are normal; PSA 2.5 ng / ml; there is no residual urine; uroflowmetry: Q max 18.0 ml / s, Q average 9.7 ml / s. Questioning according to IPSS 9 points, Qol = 2 points (satisfactory). The patient underwent TRUS of the prostate, according to which the volume of the prostate was 69 cm3.

Follow-up examination 12 months after surgery: a general urine test and a general blood test are normal; PSA level 1.8 ng / ml; there is no residual urine; uroflowmetry: Q max 19.1 ml / s, Q average 10.2 ml / s. Questioning on IPS S 8 points, Qol = 2 points (satisfactory). The patient underwent TRZ TRZ, according to which the prostate volume was 39 cm3. Dutasteride withdrawal.

Under our supervision in the period 2007-2015. there were 425 patients with BPH who underwent conservative therapy. Two groups of patients with large BPH (more than 60 cm3) were selected from the total number of patients, whose therapy was ineffective, sharply obstructive urination / cystostomy remained, and surgical treatment in the proper amount was not possible due to their aggravated somatic state. The 1st group included 17 patients over 75 years old with large BPH (more than 60 cm3).

In the 2nd group there were 15 patients with severe intercurrent pathology, the average age of which was 67 ± 1.7 years. All had severe concomitant pathology: stage 3-4 hypertension in 11 (73.3%) patients, coronary heart disease in 15 (100%), generalized atherosclerosis with episodes of cerebrovascular disease - 8 (53.3%) patients, diabetes mellitus 5 (33.3%), oncological diseases of extraurogenital localization - 2 patients (13.3%).

Standard surgical treatment in these patients had an extremely high risk. Before the start of drug therapy, all patients were examined according to standards.

The average prostate volume (Vpr) according to transrectal ultrasound (TRUS) of the prostate was 75.7 ± 5.1 cm3, PSA - 2.93 ± 0.56. In those patients who had independent urination: I-PSS - 21.3 ± 1.6 points, Qol - 4.3 ± 0.3 points, the maximum urination rate (Q max) - 8.7 ± 1.5 ml / sec, average urination rate (Q avg.) 3.8 ± 0.7 ml / sec, residual urine volume (V res) - 180.6 ± 20.5 ml.

Patients took a 5-α-reductase inhibitor dutasteride for at least 3 months, after which they underwent transurethral bipolar resection of the pancreas according to the claimed method, after surgical treatment they again resumed taking dutasteride until the size of the pancreas was reduced (no more than 40 cm3). Control examination was performed after 3 months.

Statistical processing of the results was performed using the Statistica 6.1 program. Nonparametric methods were used - Wilcoxon's test for related groups. The differences were considered statistically significant at p <0.05.

During a follow-up visit to patients after 3 months, the following data were obtained: all have self-urination, I-PSS - 12.6 ± 1.0 points, Qol - 1.9 ± 0.2 points, Q max - 17.4 ± 1, 9 ml / s, Q medium - 9.7 ± 1.2 ml / s, V res - 50.3 ± 6.3 ml.

Thus, the claimed method of combined treatment of BPH of large sizes (more than 60 cm3) in senile patients or with a pronounced intercurrent pathology has the following advantages: it improves the quality of life for each patient, reduces the number of complications of the disease, and relieves the patient from permanent cystostomy drainage .

Surgery according to the claimed method is minimally invasive, short-term, prevents blood loss, gives good functional results.

The advantages of this method:

1. The duration of the operation is 7-10 minutes.

2. The absence of significant intraoperative blood loss.

3. The use of saline.

4. Subarachnoid anesthesia with minimal drug load on the patient.

5. Minimum use of the flushing system in the postoperative period.

6. Postoperative drainage of the bladder during the day.

7. Short stay of the patient in a hospital.

8. Minor intraoperative trauma due to the use of a bipolar resectoscope.

9. The use of this method with large volumes of the prostate (more than 60 cm3), when an alternative can only be surgery that is not feasible in this category of patients.

10. High economic feasibility of the method.

The claimed method for the combined treatment of benign prostatic hyperplasia of large sizes in patients of old age or with severe intercurrent pathology was tested on large clinical material and can be recommended in urological practice.

Claims (1)

A method for the combined treatment of benign prostatic hyperplasia of large sizes in patients of old age or with severe intercurrent pathology, including transurethral resection of the prostate gland, with the creation of a canal for 12 hours and then expanding it from 11 to 1 hours, characterized in that the patient is administered preoperatively dutasteride 0.5 mg × 1 time per day for three months, after which bipolar transurethral resection of the prostate is performed in physiological p in a solution with the formation of a channel in the prostate by a loop of a bipolar resectoscope, starting from the neck of the bladder, for 12 hours of a conventional dial with a depth of 3 mm, with an extension of 11 to 1 hour, the channel formation is completed by resection of the lateral lobes of the prostate gland for 5 and 7 hours with a thickness of up to 5 mm from the neck of the bladder to the seed tubercle; in the postoperative period, the patient continues to receive dutasteride 0.5 mg × 1 time per day until the prostate volume reaches not more than 40 cm3.