I. New views and hypotheses on the causes of urinary stones
1. Abnormalities in membrane phospholipids are involved in the formation of idiopathic calcium oxalate stones
Increased membrane oxalate transport promotes the formation of hyperoxaluria, leading to calcium oxalate stones.
2, Idiopathic recurrent calcium-containing stones (IRCU): a disease that occurs at the cellular level, where oxidative/antioxidant imbalance and disturbances in mineral metabolism may contribute to the pathogenesis. Plasma levels of antioxidants are significantly reduced. It is associated with decreased blood uric acid and albumin concentrations, increased uric acid excretion, and decreased metabolic rate, which may promote urinary phosphorus excretion.
3. Relationship between inflammation and urinary tract genesis
Monocyte chemotactic protein-1 (MCP-1) is a potent chemotactic cytokine, in which the MCP-1-mediated inflammatory response is a key step in the early stages of stone formation.MCP-1-mediated inflammatory response plays an important role in the formation of non-infectious stones.
4. Hypoxia induces urinary tract formation
Hypoxia in the renal papillae can cause tubular damage and abnormal urinary acidification, which in turn promotes crystalline attachment. Hypoxia is further exacerbated if vascular damage (atherosclerosis) leads to interstitial calcification, which is involved in stone formation. Hypoxia in the papilla increases susceptibility to oxalic acid toxicity. Oxalic acid acts on tubules and interstitial cells, leading to intraluminal crystalline adhesions.
5. Polygenic genetic basis of idiopathic stones
Idiopathic stone disease is a complex, multi-causal group of diseases that result from a combination of genetic and environmental factors. Clearly recognized risk factors include hyperoxaluria, hypercalciuria, hypercitraturia, hyperuricuria, and lithogenic inhibitor deficiency. Research focusing on susceptibility genes and lead genes is also a target for future gene therapy.
Known susceptibility genes that may be relevant include:
( 1) idiopathic hyperoxaluria
( 2) idiopathic hypercalciuria
( 3) idiopathic hypocitraturia
( 4) Idiopathic calcium oxalate stone formation matrix or inhibitor abnormalities
6. Cystinuria is a genetic disorder caused by a genetic mutation.
Impaired cystine reabsorption in the renal tubules, which in turn causes decreased cystine solubility in the urine, leading to the formation of cystine stones.
7. Interrelationship between uric acid stones and calcium oxalate stones
Uric acid crystals can induce the formation of calcium oxalate crystals through an orientation attachment mechanism or promote the formation of calcium oxalate stones by decreasing the level of inhibitory factors in the urine. Soluble urates promote nucleation and aggregation of calcium oxalate crystals through salting. The lowering of urinary pH by uric acid also facilitates the formation of calcium oxalate crystals.
The urinary uric acid level of patients with calcium oxalate stones is higher than normal, and the recurrence of calcium oxalate stones can be reduced by applying allopurinol to reduce urinary uric acid.
8, obese patients with urinary abnormalities lead to high incidence of stones
(1) The secretion of various crystal formation-related components in urine increases significantly, resulting in high uric acid urine, high calcium urine, high oxalic acid urine, etc.
(2) The decrease in the content of citrate, an inhibitor of urinary stone formation, further increases the risk of urinary stone formation.
(3) The high intake of animal protein in the diet increases the acid load of the body, resulting in a decrease in urinary pH, which in turn leads to an increase in calcium excretion and a decrease in citrate excretion.
(4) High incidence of diabetes mellitus, high sugar promotes the formation of hypercalciuria.
(5) High incidence of gout, which promotes the development of hyperuricuria.
(6) Insulin resistance reduces the secretion of ammonia by the kidneys, resulting in a decrease in urinary pH (acidification), and there is an inverse relationship between body weight and urinary pH.
9. Correlation between cholesterol and urinary stones
Analysis of stone composition revealed that stones contain cholesterol, both non-esterified and esterified cholesterol. Vascular factors (associated with esterified cholesterol levels, such as atherosclerosis) may be involved in stone formation and may be an early event in stone formation.
10. Neuroendocrine correlation with urinary stones
Stressful life events lead to increased excretion of crystallization-related components (urinary calcium, oxalic acid and uric acid) in the urine. Neuropsychological factors are associated with the type of urinary stones. Neuroendocrine factors may be involved in the development of stones.
11. Role of matrix in the genesis of urinary stones
The matrix is composed of matrix proteins, aminoglucan (also known as acidic mucopolysaccharides) and carbohydrates. The specific mechanisms of matrix role in urinary stone formation include: matrix can act as an inducer of heterogeneous nucleation and thus promote nucleation; urinary proteins can strongly bind calcium and/or phosphorus, which can lead to supersaturation of calcium and/or phosphorus during matrix formation and promote crystal formation; matrix can act as a binder in the process of stone The matrix can act as an adhesive during crystal formation to reinforce the aggregation of stone crystals, or form a template to provide orderly mineralization of stone crystals, or form a fibrous network to entangle the crystals into clusters, or fill around the crystals to form agglomerates; the matrix can adhere the crystal clusters to the uroepithelial surface to form fixed particles and continue to grow; the matrix surrounding the surface of the crystals or particles forms a protective film to prevent the crystals from dissolving when they become unsaturated.
II. Recent highlights of urinary stones prevention and treatment
(i) The important role of dietary prevention
1. Drink more water
Low water intake is an important risk factor for the development of urinary stones, and crystal aggregation and retention are necessary for stone formation.
2, High calcium diet
High calcium diet can make the intestinal oxalic acid and calcium combined into non-absorbable calcium oxalate, thus reducing the absorption of oxalic acid, which is the main risk factor for the formation of urinary stones. It is important to note that a high-calcium diet decreases the incidence of urinary stones, while calcium supplementation increases the incidence of stones. A high-calcium diet combined with high water intake and supplementation with potassium, magnesium, and phosphate is necessary to prevent urinary stones, otherwise the risk of developing urinary stones increases.
3. Avoid isotonic sports drinks
Isotonic sports drinks can increase the risk of stone development by inducing the formation of stone matrix in the bladder.
4, Eat more dietary fiber
Dietary fiber intake is negatively correlated with the incidence of urinary stones, probably due to the following mechanisms: ① Decreased absorption of oxalic acid in the intestinal canal. (2) Shortening of intestinal transit time. (iii) alteration of the intestinal environment. ④Change in hormonal response. (5) Less calorie production from high-fiber foods. The combined effect of these factors reduces uric acid production and inhibits stone formation. Therefore, the consumption of dietary fiber is beneficial, but we should be careful to avoid oxalic acid-rich dietary fiber, such as chocolate, spinach, tomatoes, potatoes, beets, coffee, cola, various nuts, rhubarb, strawberries, tea and wheat bran, etc., in order to reduce the absorption of intestinal-derived oxalic acid.
5.Change of dietary habits
Stones are closely related to high animal protein, high sugar diet and habitual low water intake, preference for marinades, salty taste, preference for pickled products and other dietary habits and reduced physical activity.
(ii) The preventive effect of drugs on urinary tract stones
1, regulation of intestinal flora, treatment of stone inflammatory bowel disease in the formic acid producing bacillus oxalicus (can break down the normal flora of gastrointestinal oxalic acid) colonization is one of the causative factors of urolithiasis. By regulating the intestinal flora can reduce the intestinal source of high oxaluria, so as to achieve the purpose of treatment of stones.
2, control antibiotic abuse, prevention and treatment of stone antibiotic application can reduce the human gastrointestinal tract formic acid-producing bacilli, resulting in the occurrence of enterogenic hyperoxaluria. Control the abuse of antibiotics, especially antibiotics that can act on the gastrointestinal tract gram-negative anaerobic bacteria, such as fourth-generation quinolones moxifloxacin, etc.
3. Vitamins
(1) Vitamin C: It is a good antioxidant and can prevent the formation of calcium oxalate crystals by preventing free radical damage to kidney epithelial cells.
Vitamin B 6: Vitamin B 6 is a coenzyme that catalyzes the formation of glycine from glyoxalate. When deficient, glyoxalate cannot form glycine, which raises oxalate and contributes to the formation of calcium oxalate stones.
③Vitamin K: It can significantly reduce urinary oxalic acid content and reduce the number of renal calcium oxalate crystals.
④ Vitamin E: can prevent peroxidative damage, restore the antioxidant mechanism of renal tissue and the balance of glutathione redox system, and can inhibit the deposition of calcium oxalate crystals.
4. Thiazide diuretics
Thiazide diuretics can reduce the amount of urinary oxalic acid and intestinal absorption of oxalic acid, resulting in a decrease in urinary calcium, with the adverse effect of leading to the omission of hyperparathyroidism with normal blood calcium, aggravating diabetes, gout and erectile dysfunction.
5.Citrate root
Citrate is the main anion in the urine, and is an important inhibitor of calcium urinary stones.
6.Sodium thiosulfate for recurrent calcium-containing stones
Sodium thiosulfate may be a lithogenic inhibitor and has antioxidant damage, reversing the oxidative/antioxidant imbalance in patients with idiopathic recurrent calcium stones.
7, Oxidative thiosulfuric acid bacillus lysis therapy
Animal studies have demonstrated that specialized autotrophic and extremely eosinophilic Thiobacillus oxidans can lyse all types of urinary stones, with the best lysis effect for calcium phosphate stones. This innovative therapy can be applied to the lysis of residual stones after ESWL and to the lysis of stone crystals covered by urinary stents.
(iii) Drug lithotripsy
1. Calcium channel blocker: nifedipine
Since the ureteral wall is mainly composed of smooth muscle cells, and its peristaltic function is regulated by the intracellular calcium ion concentration, reducing the intracellular calcium ion concentration can inhibit ureteral contraction, which can relieve pain and reduce the occurrence of renal colic. Increase the rate of stone discharge.
2. α-adrenergic receptor antagonists.
The α1A receptor plays a major role in ureteral constriction. The expression density in the distal ureter is higher than that in the proximal and middle ureter. Highly selective α1 receptor antagonists such as tamsulosin can promote ureteral stone expulsion, reduce renal colic, and improve the stone expulsion rate after ESML and URL surgery.
New advances in urinary stones treatment technology
With the continuous development of minimally invasive surgical techniques, the treatment of urinary stones has undergone a radical change, changing the traditional treatment method of mainly open surgery. In recent years, the development of optoelectronic technology, biomaterials and new lithotripsy techniques have also pushed the stone treatment methods and methods forward.
(i) Open surgery
Open surgery is the traditional method of treating urinary stones. At present, surgery is still the main treatment method for complex kidney stones such as giant deerstalker, as well as for complicated kidney stones with infections, complications of renal cysts and pelvic ureteral junction stenosis deformities.
(ii) Minimally invasive treatment advances Minimally invasive treatment methods include
extracorporeal shock wave lithotripsy (ESWL)
ureteroscopy lithotripsy (URL)
percutaneous nephrolithotripsy (PCNL)
minimally invasive percutaneous nephrolithotripsy (mini-PCNL)
Laparoscopic Lithotomy (Laparoscope Lithotomy)
Extracorporeal shock wave lithotripsy (ESWL)
In February 1980, the world’s first ESWL machine was successfully developed by Dovnier, Germany, which opened a new era of non-open surgery for stone treatment in the history of human medicine.
In 1982, the first ESWL machine was developed in China, and it was used in clinical practice in 1985.
Indications: ESWL can be performed for all urinary tract stones, and is the preferred method for kidney stones <2cm in diameter and ureteral stones ≤1cm in diameter.
Contraindications: ① systemic bleeding disorders, cardiopulmonary and renal insufficiency, uncontrolled diabetes mellitus and extreme obesity; ② uncontrolled infectious diseases, the escape of bacteria after lithotripsy may cause serious urinary tract infections;
(3) Obstruction in the urinary tract below the stone site.
④Pregnant or infertile women with lower ureteral stones, because X-rays may damage the fetus, ovaries and fallopian tubes; ④Large antler-shaped stones, for which there is no adjunctive treatment in the hospital.
ESWL is a non-invasive and painless treatment for most upper urinary tract stones. If lithotripsy fails twice, the cause of the failure should be found and the treatment should be changed to other methods to avoid tissue damage caused by repeated lithotripsy.
Endolithotomy for stone extraction
1) Percutaneous nephrolithotomy (PCNL), minimally invasive PCNL (mini-PCNL)
History of percutaneous nephrolithotomy
In the 1940s, Papel and Brow were the first to use endoluminescence to remove residual stones from the nephrostomy, and in 1955, Goodwin proposed the method of percutaneous nephrostomy, which created a new era of percutaneous nephrostomy technique. 1973, Germany, the United States, Japan and other countries continued to produce and improve various rigid and bendable nephrostomy, which promoted the development of this technique.
In 1976, Fernstrom et al. were the first to use nephroscopy to successfully remove stones from the renal pelvis through a percutaneously punctured and expanded nephrostomy channel with a lithotomy basket, pioneering percutaneous nephrolithotomy.
In the 1980s, Alken and Clayman et al. successfully performed nephrolithotomy on this basis, and ultrasonic lithotripsy and electrohydraulic lithotripsy were successfully applied in PCNL, which has gradually become popular among urologists and patients worldwide because of its minimally invasive nature.
In 1997, Jackman et al. introduced the use of minimally invasive nephrolithoscopy ( F11) in children with stones. Minimally invasive nephroscopy laid the foundation for the widespread implementation of intracavitary lithotripsy.
After 1982, PCNL surgery was carried out in Beijing, Guangzhou and Nanjing in China.
The traditional PCNL: percutaneous nephrostomy was performed first, and then lithotripsy was performed one to two weeks later. The caliber of nephrostomy was thicker, and the dilated channel reached F26-30 (10 mm in diameter) or more, which could easily damage the interlobular vessels or tear the calyx neck and cause complications such as intraoperative and postoperative renal hemorrhage and urinary extravasation.
In 1992, Li Xun from the Department of Urology of the First Affiliated Hospital of Guangzhou Medical College put forward the idea of microstomy percutaneous nephrolithotomy, and innovated the technique of percutaneous nephrostomy microstomy and percutaneous nephrostomy ureteroscopy to retrieve stones, but it still needs the second stage of stone retrieval, and the stone retrieval rate is low.
Minimally invasive PCNL: In 1998, Li Xun et al. proposed a minimally invasive PCNL with Chinese characteristics, i.e., percutaneous nephrostomy with working channel F14 or F16, using F8/9.8 ureteroscope instead of nephroscope to enter the renal collecting system or upper ureter through the working channel for first-stage lithotripsy, which not only causes less damage and low risk, but also broadens the scope of application of the operation and promotes the development of PCNL. It is the ideal minimally invasive treatment for complex stones in the upper part of the kidney and ureter.
PCNL has completely changed the awkward situation that urologists can only remove stones from deer-horn-shaped kidney stones by open surgery, which is of great significance especially for patients with recurrent stones after open surgery and those who cannot tolerate open surgery.
2) Ureteroscopic lithotripsy (URL)
History of ureteroscopic lithotripsy
In 1977, Goodman reported the use of pediatric cystoscopy as a ureteroscope to view the ureter in adults.
In 1979, Lyon et al. and Richard Wolf designed and produced a special ureteroscope, F13, with two types of sheaths, F14.5 and F16.
In 1980, Perez-Castro successfully manufactured the first F11 ureteroscope and performed ureteral examination and lithotripsy with this scope.
Between 1983 and 1985, ureteroscopes were first introduced to China in Beijing and Guangzhou,
After the 1990s, the ureteroscope was continuously improved, and the introduction of fiber optic guide beam greatly reduced the caliber of ureteroscope. The introduction of the fiberoptic beam has greatly reduced the caliber of ureteroscopes. The caliber of endoscopes has been slimmed down and the types of endoscopes (rigid, semi-rigid, and flexible) have been diversified.
Ureteroscopy has significantly changed the situation in the treatment of urinary tract stones and has established its place in endoluminal urology. At present, URL has irreplaceable superiority in the treatment of middle and lower ureteral stones,
3.Intracorporeal lithotripsy system
The ultimate realization of intracavitary lithotripsy depends on the use of various lithotripters, and the progress of lithotripter technology is complementary to the progress of endoscopic technology.
1）Liquid lithotripter
Principle: Electrohydraulic lithotriptor (EHL) is a lithotriptor based on spark gap technology, which was widely used in the 1980s.
Disadvantages: The non-directional spread of electrode heat, when the electrode is not in contact with the stone, the sparks generated may damage the conical lens of the endoscope, and may also damage the urinary collection system causing perforation or bleeding. Therefore, EHL is no longer used as a routine treatment for upper urinary tract stones.
2）Ultrasonic lithotripter
Principle: The ultrasonic lithotripter generates high frequency oscillation through its probe, which leads to ultrasound, which is transmitted to the head end of the probe rod, causing vibration and fragmentation of the stone in contact with it,
Disadvantages: The efficiency of lithotripsy is low, and it is not widely accepted by clinicians.
3) Laser (Ho: YAG) lithotripter
A review of the use of laser in urology
In 1966, Parsons et al. experimented the effect of pulsed ruby laser on open tissues of dogs, which was the first use of laser in urology.
In 1984, Beisland and Sander used the Nd:YAG laser for prostate cancer treatment, respectively,
In 1992, Johson et al. reported an experimental study on the use of holmium laser in urology, which pioneered the use of holmium laser in urology,
In 1995, Bagley first reported the use of holmium laser as an intracavitary lithotripter for the treatment of upper urethral calculi.
Principle: The holmium laser is mainly used to break up stones by gas cavitation due to the photothermal effect,
Holmium laser has a high absorption coefficient in water and the most water content in the tissue, therefore, the main energy of holmium laser is concentrated in the surface layer of the tissue, which gives the holmium laser excellent cutting and tissue removal ability.
Advantages: ①High primary lithotripsy rate; ②Significantly shorter hospital stay and stone evacuation time; ③Simultaneous treatment of polyps, ureteral and urethral strictures, and bleeding; ④Short operation time, less tissue damage, and facilitated stone evacuation after surgery, increasing the cure rate.
Disadvantages: The photothermal effect of holmium laser makes it easy to cause pelvic and ureteral damage and perforation during accidental exposure, and it is slightly underpowered for larger stones in the renal collecting system. The holmium laser is less likely to perforate the ureter at a distance of more than 1 mm from the ureteral wall.
So far, holmium laser is the ideal system for in vivo lithotripsy and is currently the first choice. Holmium laser lithotripters can not only break up stones of various compositions, densities and locations, but also cauterize polyps and cut through narrow ureteral walls to achieve similar results as open surgery.
(4) Combined ultrasonic pneumatic ballistic lithotripsy system
In 1986, the world’s first intracavitary pneumatic ballistic lithotripter was developed by EMS, Switzerland,
In 2001, the third generation of lithotripsy system (EMS III) was developed, which brought the lithotripsy into the era of simultaneous minimally invasive lithotripsy and lithotripsy.
Principle: The combined lithotripter consists of a newly invented high performance ultrasonic lithotripter system, a powerful pneumatic ballistic lithotripter system and a negative pressure adsorption device, with a special handle to combine ultrasound, pneumatic ballistic lithotripter and adsorption device into four lithotripter and lithotripter modes: ① using pneumatic ballistic + ultrasound + negative pressure adsorption at the same time; ② using pneumatic ballistic + negative pressure adsorption; ③ using pneumatic ballistic lithotripter alone; ④ using ultrasound + negative pressure adsorption alone. negative pressure adsorption. ,
Advantages: ① Synergistic effect of two highly efficient lithotripsy systems; can break large or particularly hard stones; ② Synchronous lithotripsy function; ③ Maintain low or no pressure in the urinary collection system by negative pressure suction during lithotripsy and lithotripsy, avoiding the potential risk of infection due to intrarenal hypertension which may be caused by intrarenal flushing, thus improving the safety of the procedure. ④There is no thermal effect during treatment, which will not damage tissues and mucous membranes, and will not destroy the endoscope. ⑤The operation time and stone treatment time are shorter than those of other lithotripters. It is more effective than pneumatic ballistic or ultrasound lithotripsy alone.
Disadvantage: It is not possible to use combined lithotripsy in ureteroscopy because of the small working channel.
Combined ultrasound and pneumatic ballistic lithotripsy for stone removal is a safe method of lithotripsy.
4 Laparoscopic ureterotomy for lithotripsy
Wickham was the first to use laparoscopic techniques to perform successful ureterotomy for stone extraction via the retroperitoneal route in 1979.
The introduction of television laparoscopy in the 1990s led to the rapid development of laparoscopic techniques for the treatment of upper urinary tract stones.
Indications: Extra-renal pelvic stones that cannot be treated with ESWL and URL for various reasons or failed treatment,
Large, hard or long-embedded stones in the middle and upper ureter with significant peripheral fibers and granulomatous growth
Laparoscopic treatment route
Transperitoneal route: With large space and clear anatomical landmarks, upper, middle and lower ureteral stones can be treated at the same time, and bilateral ureteral stones can be treated at the same incision, but the scope of surgery is large, contamination of the abdominal cavity is large, and may damage the abdominal organs and intestinal adhesions after surgery, and the upper and middle ureteral segments are not as well exposed as the retroperitoneal route.
The retroperitoneal route has the disadvantages of small operating space, complicated establishment of pneumoperitoneum, and slow absorption of postoperative exudate, but the access is straightforward, easy to separate and reveal the kidney and find the ureter, and the urologist is more familiar with the retroperitoneal route. Therefore, this route is mostly used for laparoscopic ureteral surgery.
Controversy: Some scholars believe that it is not significant in the treatment of urinary tract stones because: firstly, the equipment is more expensive and the learning curve is long; secondly, it is simpler and easier to use URL or mini-PCNL for patients who are suitable for laparoscopic surgery.
IV Summary
With the development of science and technology, most urinary stones can be treated in a minimally invasive and less painful way.
ESWL is still the preferred minimally invasive treatment option for most upper urinary tract stones.
Ureteral stones can be treated by ureteroscopy or lithotripsy, ESWL or a combination of both depending on the nature, location, size and number of stones, the degree of urinary tract obstruction, renal function and the technical conditions of the equipment,
Ureteroscopic lithotripsy is more effective with laser lithotripsy.
Minimally invasive PCNL with pneumatic ballast lithotripsy, holmium laser lithotripsy or combined ultrasound and pneumatic ballast lithotripsy is the preferred minimally invasive option for the treatment of complex stones in the upper part of the kidney and ureter.
Laparoscopic surgery: It is another alternative for the treatment of upper urinary tract stones, which can replace most open surgeries and represents the direction of minimally invasive urological development.
The combination of minimally invasive procedures can cure more than 95% of urinary stones.
Open surgery for stone extraction is suitable for cases where minimally invasive treatment such as ESWL or URL has failed, or where there are complications and congenital malformations of the pelvic-ureteral junction.
In conclusion, the choice of treatment method should take into account not only the stone site, size and density, but also the hospital’s equipment, the physician’s technical level, the patient’s general condition, the patient’s willingness to treat and the cost of treatment, in order to make a reasonable and appropriate treatment method.