Lower urinary tract lithiasis is among the oldest of known human maladies, with an often dubious and barbaric legacy spanning the full course of recorded human history. Notable sufferers of lower urinary tract lithiasis include Isaac Newton, Benjamin Franklin, Francis Bacon, John Marshall, Peter the Great, Louis XIV, George IV, Boerhaave, Scarpa, and Napoleon Bonaparte and his descendants (Ellis, 1969; Khai-Linh and Segura, 2006).

In 1905, Shattock described what may be the earliest known case of lower urinary tract stone disease, when excavation of gravesites in Egypt revealed a 6.5-cm bladder calculus within the pelvis of the body of a 16-year-old boy, dating back to approximately 4800 BC. Given that the methods of burial diverged from Egyptian tradition, little else about the background of the remains could be surmised (Shattock, 1905).

Although little is known about the understanding and treatment of urinary lithiasis in ancient civilizations, it is apparent that the affliction was so commonplace by the 5th century BC that it warranted specific mention in the works of the prolific Greek physician Hippocrates (Pardalidis et al, 2007; Herr, 2008). Perhaps the most famous instance is his proclamation within the oath bearing his name, stating “I will not cut for stone, even for patients in whom the disease is manifest; I will leave this operation to be performed by practitioners, specialists in this art” (Adams, 1938). Whether this was an early acknowledgment of the emerging field of urology or a caution for physicians to exclude themselves from the lowly butchery perpetrated by early lithotomists remains a matter of debate (Herr, 2008).

Vague descriptions of urinary stone extraction can be found in ancient texts of the Roman, Greek, Persian, and Hindu civilizations; however, the term lithotomy was not coined until 276 BC by the Greek Ammonius, and the procedure was not described in detail until the writings of the Roman Cornelius Celsus nearly 300 years later in AD 20 (Pardalidis et al, 2007; Herr, 2008).

Accounts of the Celsian method of cystolithotomy conjure up terrifying images of harrowing, regularly fatal interventions in which the patient, generally a child no older than 14, would be bound or held fast to a table with his legs severely jackknifed and abducted to expose the perineum. One or two fingers would be inserted into the rectum to locate the stone and manually draw it down toward the bladder neck. The perineum was then incised widely with a chisel-like razor, rending the flesh until the bladder was entered, and the stone was then extracted using a forceps or a hook. If the patient were lucky enough to survive the operation before exsanguinating, the surgeon would leave this wound open, applying a dressing of oil-soaked wool or freshly killed and gutted fowl (Moore, 2005; Pardalidis et al, 2007; Trompoukis et al, 2007; Herr, 2008). Recovery was often as agonizing as the initial procedure, when leakage of urine through the wound proved excruciating for the young patient (Trompoukis et al, 2007). Infection, incontinence, impotence, and fistula formation were all-too-common morbidities of the procedure, and nearly half of all patients died soon after the operation (Moore, 2005; Herr, 2008).

The grotesque and morbid nature of the procedure, however, hardly served to dissuade many sufferers of bladder stones from submitting themselves to the procedure. Galen and other notable physicians of the day began performing lithotomy, thereby legitimizing the procedure to some degree. In addition, midwives underwent instruction and education in the technique to offer treatment to female patients. By the Middle Ages the practice of lithotomy was a booming business, performed mostly by roving lithotomists of varying skill and competence who would ply their trade for a fee, performing the procedure on as many patients as possible before being driven out of town as their patients expired en masse (Herr, 2008).

Although small refinements were made to the procedure over the ensuing centuries the practice of lithotomy remained largely unchanged for nearly 1500 years (Herr, 2008). In Paris, during the early 16th century, Jacques de Beaulieu, a poorly trained and uneducated monk known more famously today as the subject of the children’s song “Frere Jacques” than as a pioneering surgeon of his time, refined the techniques of Pierre Franco, using a lateralized perineal approach that proved a slightly less morbid operation. Although many surgeons of the time dismissed Frere Jacques as a quack, he became a prolific practitioner of lithotomy, providing his services to over 5000 patients throughout Europe (Kelly, 1909; Bail, 1932; Moore, 2005; Herr, 2008). De Beaulieu’s methods were later adopted by William Cheselden, a Briton, who perfected the techniques of his forebears, introducing new instrumentation and an informed anatomic approach that reduced the mortality of lithotomy to less than 10% (Gross and Gross, 1876; Moore, 2005; Herr, 2008).

Fortunately, modern advances in surgical technology and aseptic technique have transformed this once deadly affliction into an eminently manageable and rarely fatal disease process. In addition, changing diets and industrialization have served to significantly reduce the incidence of lower urinary tract calculi, especially in the Western world.

Bladder Calculi

Bladder stones are the most common manifestation of lower urinary tract lithiasis, currently accounting for 5% of all urinary stone disease and approximately 1.5% of urologic hospital admissions in industrialized Western nations (Smith and O’Flynn, 1975; Schwartz and Stoller, 2000; Papatsoris et al, 2006). Bladder calculi in nonendemic areas are typically found in adults and almost always in association with other disease processes resulting in urinary stasis or the introduction of a foreign body (Schwartz and Stoller, 2000). However, in endemic regions, bladder calculi often arise in children in whom a major anatomic abnormality does not coexist; in these regions, dietary intake and socioeconomic factors primarily influence the formation of bladder calculi (Andersen, 1962; Asper, 1984).

Primary Bladder Calculi

Once common in Europe and the United States, primary bladder calculi of childhood have been practically eliminated by the spread of industrialization and the modernization of the Western diet over the past 100 years (Van Reen, 1980; Schwartz and Stoller, 2000). However, childhood bladder lithiasis remains common in endemic regions, throughout a stone belt reaching from northern Africa, through the Middle East and the Balkans, and into India, Japan, Thailand, and Indonesia; they are uncommon in the southern hemisphere (Valyasevi and Van Reen, 1968; Valyasevi and Dhanamitta, 1974; Thalut et al, 1976; Asper, 1984; Teotia and Teotia, 1990; Hesse and Siener, 1997; Kamoun et al, 1999; Rizvi et al, 2003; Ali and Rifat, 2005). It is important to note that the term primary in this context refers to the fact that these stones develop in the absence of any known functional, anatomic, or infectious factors and does not necessarily imply that stones have formed de novo in the bladder (Andersen, 1962).

Primary bladder calculi are most common in children younger than the age of 10, with a peak incidence at 2 to 4 years of age (Valyasevi and Van Reen, 1968; Thalut et al, 1976; Teotia and Teotia, 1990; Ali and Rifat, 2005). The disease is much more common in boys than in girls, with ratios ranging from 9 : 1 to as high as 33 : 1 in areas of India (Andersen, 1962; Thalut et al, 1976; Van Reen, 1980; Kamoun et al, 1999; Rizvi et al, 2003). Stones are usually solitary and, once removed, rarely recur (Valyasevi and Van Reen, 1968; Van Reen, 1980; Teotia and Teotia, 1990). Ammonium acid urate, calcium oxalate, uric acid, and calcium phosphate are the most common components of primary bladder calculi (Valyasevi and Van Reen, 1968; Teotia and Teotia, 1990).

Predisposition to the formation of bladder calculi appears to arise from a number of nutritional and socioeconomic factors. Children in endemic regions often consume a predominantly cereal-based diet that is poor in animal protein and low in phosphate (Thalut et al, 1976; Van Reen, 1980; Teotia and Teotia, 1990). In some regions, infant diets consist only of predigested rice that is first chewed by the mother, as well as breast milk, both of which are critically low in protein and phosphate (Andersen, 1962; Valyasevi and Van Reen, 1968; Thalut et al, 1976). Low dietary intake of phosphate not only leads to hypophosphaturia but also to hyperammonuria, promoting the precipitation of both calcium oxalate and ammonium acid urate (Noe and Stapleton, 1987; Teotia and Teotia, 1990). In addition, in the poor villages of Thailand, tampala and bamboo shoots, both of which are rife with bioavailable oxalate, are a frequent staple for infants (Valyasevi and Dhanamitta, 1974), which when combined with low dietary intake of vitamins B₁, B₆, and magnesium can lead to hyperoxaluria and formation of calcium oxalate stones. Vitamin A deficiency can also lead to urothelial degeneration, which may also promote stone formation (Teotia and Teotia, 1990).

In addition, substandard living conditions and poor sanitation can lead to a paucity of adequate drinking water and an increased prevalence of diarrhea, leading to dehydration and supersaturation of stone-forming compounds in the urine (Valyesevi and Van Reen, 1968; Thalut et al, 1976; Van Reen, 1980; Schwartz and Stoller, 2000).

Children suffering from primary bladder calculi rarely present acutely. There is often a prodrome consisting of the passage of sandy urine or the presence of dusty crystals in dried urine that heralds the precipitation of urinary solutes. Children often complain of vague abdominal discomfort, dysuria, frequency, and hematuria. Pulling of the penis is considered by some to be pathognomonic, because it indicates the child is suffering from stranguria; frank urinary retention, however, is very rare. In some cases, rectal prolapse and conjunctival hemorrhages may develop as the result of intense straining to void (Thalut et al, 1976; Teotia and Teotia, 1990; Ali and Rifat, 2005).

Prevention consists mostly of dietary modification. In Thailand, phosphate supplementation was found to significantly reduce oxalate crystalluria, even without concomitant reduction in oxalate intake (Valyasevi and Dhanamitta, 1974). However, other authors suggest a transition to a mixed-cereal diet with milk supplementation as the most practicable solution for bladder stone prevention (Teotia and Teotia, 1990).

Key Points

Primary Bladder Calculi

• Primary bladder calculi are more common in children exposed to low-protein, low-phosphate diets.

• Primary bladder calculi rarely recur after treatment.

Secondary Bladder Calculi

Bladder calculi of the type commonly encountered throughout the Western world are typically found in men older than the age of 60 and usually in concert with lower urinary tract obstruction, which prevents complete bladder emptying (Douenias et al, 1991; Takasaki et al, 1995; Hesse and Siener, 1997; Yasui et al, 2008). Over the past 4 decades, the overall incidence of bladder calculi appears to have stabilized or decreased among males and increased slightly for females; these trends are likely due to the increase in the elderly population as life expectancies lengthen, as well as an overall increase in the number of female genitourinary procedures performed annually (Schwartz and Stoller, 2000; Terai et al, 2008; Yasui et al, 2008).

Bladder calculi may arise de novo within the bladder or may result from the maturation of stone nidi that migrate from the upper tracts and subsequently fail to be spontaneously voided. The latter appears to be far less common than initially postulated, because only 3% to 17% of patients will report a history of renal colic to suggest the passage of a calculus from the upper tracts (Aird, 1957; Smith and O’Flynn, 1975; Douenias et al, 1991). The frequent absence of calcium oxalate in the nucleus of most bladder stones further suggests against an upper tract origin (Douenias et al, 1991; Vanwaeyenbergh et al, 1995). The pathogenesis and composition of bladder calculi depend largely on the inciting pathologic process and the presence or absence of infection.

Bladder Outlet Obstruction and Acquired Lower Urinary Tract Pathologic Process

Bladder outlet obstruction resulting in incomplete emptying and the retention of stone fragments is the most common predisposing factor for bladder stone formation in non-neurogenic bladders and is present in 45% to 79% of all patients diagnosed with vesical calculi (Smith and O’Flynn, 1975; Douenias et al, 1991; Takasaki et al, 1995). In men, outlet obstruction is generally related to benign prostatic hyperplasia, whereas urethral kinking from a cystocele or pelvic organ prolapse is often the culprit in females (Smith and O’Flynn, 1975; Douenias et al, 1991; Sarica et al, 1994; Nieder et al, 1998; Schwartz and Stoller, 2000; Papatsoris et al, 2006). Urethral stricture, bladder neck contracture, and bladder diverticula are also secondary causes that may interrupt normal voiding patterns (Smith and O’Flynn, 1975; Douenias et al, 1991).

The composition of stones resulting from anatomic obstruction varies with geography and ethnicity. In Europe, struvite, calcium phosphate, and uric acid predominate, whereas in Japan uric acid calculi are uncommon and calcium stones are increasing in incidence, now representing 72% of all stones in a recent series. Calcium oxalate comprises the majority of bladder stones found in the United States, although uric acid stones predominate among the American Jewish population (Smith and O’Flynn, 1975; Hesse and Siener, 1997; Douenias et al, 1991; Papatsoris et al, 2006; Yasui et al, 2008). Stones are usually solitary, although multiple stones may exist in 25% to 30% of patients (Sarica et al, 1994).

Intravesical Foreign Body

Foreign material within the bladder provides an ideal nidus for stone formation and is responsible for the majority of bladder calculi diagnosed in females (Smith and O’Flynn, 1975; Schwartz and Stoller, 2000; Papatsoris et al, 2006). Often, a foreign body within the bladder will initially encrust with calcium oxalate, as a result of the normal stasis that occurs with the storage of urine. Should infection supersede, rapid coalescence of the stone may occur as struvite is deposited on the nascent stone (Dalton et al, 1975; Khan and Wilkinson, 1990; Vanwaeyenbergh et al, 1995; Schwartz and Stoller, 2000).

The vast majority of intravesical foreign bodies result from iatrogenic interventions, although self-mutilation plays a role in a minority of patients (Dalton et al, 1975; Douenias et al, 1991; Schwartz and Stoller, 2000); complications resulting from urogynecologic interventions predominate. Inadvertent violation of the bladder with suture material during suspension or sling procedures is a common source of an intravesical foreign body. Often this error is not detected intraoperatively, underscoring the importance of thorough cystoscopic inspection before the conclusion of the procedure (Zderic et al, 1988). Along with the rise in popularity of incontinence surgery involving synthetic mesh, such as tension-free vaginal tape procedures, there has been a noted increase in calculi forming on portions of the mesh that have eroded into the bladder (Chamary, 1995; Koelbl et al, 2001; Irer et al, 2005; Mustafa and Wadie, 2007). In addition, erosion of wire suture used for cerclage has been reported (Ehrenpreis et al, 1986). Stone encrustation of migrated intrauterine devices, pessaries, and contraceptive diaphragms have also been reported (Staskin et al, 1985; Khan and Wilkinson, 1990; Mahazan, 1995; Chow et al, 1997; Maskey et al, 1997; Schwartz and Stoller, 2000; Demirci et al, 2003).

In men who have undergone radical retropubic prostatectomy, formation of stone on eroded silk sutures used to ligate the dorsal vein complex have been reported (Scheidler et al, 1990; Miller et al, 1992). In addition, necrotic tissue resulting from chemical ablation of the prostate for benign prostatic hyperplasia has been cited as a nidus for stone formation (Ikari et al, 2005), as has the presence of intraprostatic stents (Chiu et al, 1991; Squires and Gillatt, 1995). Erosion of an inflatable penile prosthesis and artificial urinary sphincters resulting in stone encrustation have also been reported (Dupont and Hochman, 1988; Barroso et al, 2000; Bartoletti et al, 2000).

The development of bladder calculi is an infrequent complication of long-term urinary tract drainage. Encrustation of short-term ureteral stents are a common finding, although significant intravesical stone formation may occur in instances in which the stent is left resident for an extended period of time (Giannakopoulos et al, 2001; Damiano et al, 2002; Hao et al, 2008; Vanderbrink et al, 2008; Waters et al, 2008). Long-term bladder drainage may also result in bladder lithiasis, with a reported incidence of 0.07% to 2.2% in patients with chronic indwelling catheters (Kohler-Ockmore and Feneley, 1996). In instances in which Foley balloons burst intravesically, retained fragments frequently lead to subsequent stone formation (Chute, 1962; Smith and O’Flynn, 1975). Even patients who perform clean intermittent catheterization may not be immune, because inadvertent introduction of hair into the bladder with the passage of the catheter may provide a nidus for stone formation (Derry and Nuseibeh, 1997).

On rare occasions, intravesical calculi may also arise as a result of the migration and erosion of foreign bodies unrelated to genitourinary manipulation. These include orthopedic cement, surgical clips, ventriculoperitoneal shunts, and abandoned gallbladder stones resulting from spillage during cholecystectomy (Radford and Thomson, 1989; Chia and Ross, 1995; Maier and Treu, 1996; Eichel et al, 2002).

Neurogenic Bladder and Spinal Cord Injury

Neurogenic bladder resulting from spinal cord injury or myelomeningocele places patients at increased risk of bladder stone formation. For adults with spinal cord injury the risk for bladder stone formation peaks at 3 months after the initial injury, and within 10 years 15% to 30% of patients will have formed at least one stone (Chen et al, 2001). Unfortunately, once a patient has formed one stone, the risk of forming a subsequent stone quadruples (Ord et al, 2003). The level and severity of the spinal cord injury appears to be closely correlated with the risk of bladder stone formation, especially after the first year (Chen et al, 2001; Sugimura et al, 2008). This is possibly due to the inability of quadriplegics with complete cord lesions to perform intermittent catheterization themselves, relying instead on caretakers or a chronic indwelling catheter for bladder management (Sugimura et al, 2008).

Indeed, the manner in which the bladder is managed in spinal cord injury appears to have a significant impact on the risk of stone formation. One large study of over 450 patients noted that the use of clean intermittent catheterization was associated with a significant reduction in the risk of bladder stone formation, with an annual risk of 0.2%, compared with 4% in those patients managed by a chronic indwelling catheter (Ord et al, 2003). This finding has been corroborated by other reports (Mitsui et al, 2000; Chen et al, 2001). In addition, the use of clean intermittent catheterization is associated with a 40-fold decrease in the risk for hospital admissions due to bladder calculi (Ord et al, 2003). As such, clean intermittent catheterization is the recommended form of bladder management in all patients in whom it is feasible (Feifer and Corcos, 2008). However, for patients who must rely on chronic indwelling catheters, suprapubic cystotomy provides no benefit over urethral catheterization in terms of the development of bladder calculi, although patients often report greater satisfaction with the former (Ord et al, 2003; Sugimura et al, 2008).

The incidence of bladder calculi in children with neurogenic bladder is far lower than in adults, developing in only 5% to 8% of nonaugmented children performing clean intermittent catheterization. The incidence of bladder stones is slightly higher, however, in children who catheterize through a Mitrofanoff conduit than those who catheterize per urethra (Barroso et al, 2000).

Bladder Calculi in Transplant Patients

Bladder calculi are an uncommon complication of solid organ transplantation, occurring primarily in pancreatic allografts drained via the bladder. In all reported instances, nonabsorbable suture material or surgical clips have been found to serve as the nidus for stone formation (Hakim et al, 1997; Del Pizzo et al, 1998; Hahnfeld et al, 1998; Rhee et al, 1999; Schwartz and Stoller, 2000). Stone formation may be potentiated by low serum pH due to bicarbonate leak as well as urinary stasis and incomplete bladder emptying due to diabetic uropathy. When combined with an increased coincidence of bacteriuria due to colonization of included duodenal segments and the effects of immunosuppression, the ideal milieu for calculus formation can arise (Rhee et al, 1999). The reported incidence of bladder calculi in pancreatic allograft recipients ranges from 0.5% to 10% (Hakim et al, 1997; Del Pizzo et al, 1998; Hahnfeld et al, 1998).

Bladder calculi may also occur after renal transplantation without simultaneous pancreatic transplant, with incidences ranging from 0% to 5% in the literature. In most instances, suture material serves as the nidus for stone formation; however, although two studies identified the development of calculus material on absorbable polyglactin sutures, another large series found calculus formation only occurred in cases in which nonabsorbable suture material had been used for the ureterovesical anastomosis (Leunissen et al, 1987; Klein and Goldman, 1997; Rhee et al, 1999; Lipke et al, 2004).

Key Points

Secondary Bladder Calculi

• Secondary bladder calculi are generally associated with bladder outlet obstruction.

• Patients with spinal cord injury are at increased risk of bladder stone formation.

• Intermittent catheterization decreases the risk of bladder stone formation over an indwelling catheter.

Augmented Bladders and Urinary Diversion

Bladder and pouch stones are a known complication of augmentation cystoplasty and urinary diversion. They arise from a complex interplay of functional, anatomic, metabolic, and infectious factors.

Bladder Augmentation

The reported incidence of bladder calculus after augmentation cystoplasty ranges from 10% to as high as 52.5% (Edin-Liljegren et al, 1996; Kaefer et al, 1998; Kronner et al, 1998; Bertschy et al, 2000; Mathoera et al, 2000; Madersbacher et al, 2003). Unlike traditional adult urolithiasis, females are more commonly affected than males, likely owing to the high incidence of cloacal abnormality requiring additional procedures beyond augmentation (Mathoera et al, 2000). Mean time to the formation of first stone ranges from 24.5 to 68 months, and after the first incidence the risk of recurrence is 19% to 44% (Blyth et al, 1992; Palmer et al, 1993; Kronner et al, 1998; Mathoera et al, 2000; Woodhouse and Lennon, 2001; DeFoor et al, 2004; Hensle et al, 2004).

Because bacteriuria and urinary tract infection are commonplace after augmentation cystoplasty, it is not surprising that the vast majority of associated calculi contain a significant struvite component (Blyth et al, 1992; Palmer et al, 1993; Kaefer et al, 1998; Hensle et al, 2004; Robertson and Woodhouse, 2006). Interestingly, however, struvite is not the predominant component in most infection-related stones found in augmented bladders; rather, one study found a predominance of calcium phosphate in these stones, which is likely due to the comparatively lower pH required for precipitation of calcium phosphate, as compared with struvite. In addition, up to 14% of patients were found to have noninfectious stones, consisting of calcium phosphate and calcium oxalate with no struvite component (Allison et al, 1985; Robertson and Woodhouse, 2006). Uric acid calculi are rare in augmented bladders (Blyth et al, 1992; Palmer et al, 1993; Hensle et al, 2004; Robertson and Woodhouse, 2006). The treatment of recurrent urinary tract infections with antibiotics may have the deleterious effect of eradicating Oxalobacter formigenes within the gut, leading to an increase in intestinal oxalate absorption and hyperoxaluria (Robertson and Woodhouse, 2006).

However, infection is just one aspect of the milieu that can lead to stone formation in augmented patients. As in nonaugmented bladders, urinary stasis and incomplete bladder emptying serve to potentiate bladder stone formation. Factors that may contribute to stasis include bladder neck reconstruction, artificial urinary sphincter placement, and urethral sling procedures, all of which are designed to provide hypercontinence (Kronner et al, 1998). In addition, catheterization through nondependent access, such as through Mitrofanoff channels, is associated with a higher risk of stone formation (Kaefer et al, 1998; Kronner et al, 1998; Barroso et al, 2000). Dehydration, hypocitraturia, hypercalciuria, as well as high urinary pH in intestinal augments may also contribute to stone formation (Woodhouse and Robertson, 2004).

The role of intestinal mucus in stone formation remains controversial. Bladder calculi are found almost exclusively in patients who have undergone augmentation cystoplasty with ileum or colon and are rarely encountered after augmentation using stomach or ureter or after autoaugmentation (Kaefer et al, 1998; Kronner et al, 1998; Bertschy et al, 2000; Mathoera et al, 2000; DeFoor et al, 2004; Woodhouse and Robertson, 2004). Although some cite the production of enteric mucus as a predisposing factor in bladder stone formation, both as a nidus for stone formation and as a promoter of bacterial biofilm formation (Bruce et al, 1984; Blyth et al, 1992; Khoury et al, 1997), others have challenged that notion. Two recent studies have evaluated the role of regular bladder irrigation to promote mucus washout; neither found a significant reduction in the incidence of bladder calculi, suggesting that mucus production has little effect on stone formation (Brough et al, 1998; Mathoera et al, 2000). Instead, other authors suggest that it is the low urinary pH associated with gastric segments that inhibit bacterial growth and the precipitation of struvite that explains their decreased propensity for stone formation (Kaefer et al, 1998; Kronner et al, 1998). Indeed, some of the few accounts of vesical stone formation after gastrocystoplasty have resulted in patients on histamine blockade, which raises the urinary pH (Kaefer et al, 1998).