LONG-TERM SURVEY OF 538 PATIENTS WITH UPPER URINARY TRACT STONE

LONG-TERM SURVEY OF 538 PATIENTS WITH UPPER URINARY TRACT STONE’

By R. E. WILLIAMS, F.R.C.S.(Ed.) Senior Urological Registrar, Department oJ Urology, The General litfirtitmy

and St James’s Hospitrrl, L e e h

RECURRENCE of upper urinary tract stone is often delayed many years and can be detected only by long-term follow-up. The complicated pattern of stone formation and recurrence makes a prolonged survey difficult for calculi may follow one another in quick succession or be delayed many years, either or both kidneys may be affected and often the distinction between true and false recurrence is uncertain. Most surveys have been limited to the investigation of recurrence within a short period following specific operations or groups of operations. In recent years there have been few investigations into the frequency of post-operative stone recurrence and no attempt to assess stone formation and recurrence over a long period in the life history of a large number of patients.

This paper assesses the incidence of stone formation and recurrence in a large series of patients, all of whom had a history of calcium-containing upper urinary tract stone for a minimum period of ten years. The known atiological factors are described and recurrence rates for various operations are compared.

General Incidence of Stone Formation.-It is difficult to estimate the true incidence of renal lithiasis in the general population for calculi may be symptomless and undetected, or may appear only as an incidental finding on X-ray; patients may pass small calculi without attending their medical practitioner or may be treated by him and not referred to hospital for urological examination. A definite geographical distribution for urinary calculi has been observed though there were no causative factors common to the areas of high incidence. The incidence may alter at different times in the same area and Grossman (1938) observed the extreme increase of oxalate stone formation in Central Europe from 1924 to 1930. In some districts the incidence increased one-thousand-fold and he considered that this could not be due solely to better diagnostic facilities.

Boyce, Garvey, and Strawcutter (1956) found, from questionnaires sent to hospitals throughout the United States of America, that 9.47 persons per 10,000 (0.1 per cent.) of the general population were admitted to hospital in 1952 for upper urinary tract and bladder stone. Evidence of geographical distribution was found, the individual States varying from four to nineteen persons per 10,000 of population. The incidence was lower among children than adults and lower among negroes than whites living in the same area. Rosenow (1940) found rznal calculi present in 5.4 per cent. of 239 autopsies, but most were small symptomless calculi. Anderson (1963) reviewed the results of 26,834 autopsies performed at the General Infirmary, Leeds, between 1928 and 1961, on patients not admitted for treatment of stone and who had no previous history of this condition. Macroscopic renal calculi were found in forty-eight autopsies, an incidence of 0.18 per cent.

Previous Investigations,-Table I shows the post-operative recurrence rates of the largest surveys. Among the earlier reviews, Cabot and Crabtree (1915) reported over 50 per cent. recurrence following nephrotomy and pyelolithotomy. Brongersma’s paper, read to the

Read at the Nineteenth Annual Meeting of the British Association of Urological Surgeons at Lccd.;. July 1963.

416

U P P E R U R I N A R Y T R A C T S T O N E 41 7

International Society of Urology in 1924, showed recurrence rates of 35.5 per cent. for nephrolithotomy and 23.6 per cent. for pyelolithotomy in 100 patients whom he had re-examined carefully. The superiority of partial nephrectomy was emphasised by Hamilton Stewart (1 952), who examined eighty-seven patients following this operation and found recurrent calculi in only 6.8 per cent. Sutherland (1954) reviewed 345 stone-forming patients for post-operative recurrence, assessed previous investigations, and drew attention to some of the factors which produced wide variation in reported recurrence rates. He re-examined 189 patients and found 62.5 per cent. recurrence after nephrolithotomy, 47 per cent. recurrence after pyelolithotomy, and 37 per cent. after ureterolithotomy.

Writer Year

TABLE I

Previous Investigations of Post-operative Recurrence

I Percentage Recurrence following Number ~

Partial Cases Re- examined Nephro- Pyelo- Uretero-

l lithotomy lithotomy lithotomy ' Nephrec- I I I 1 tomy

~ ~~~~~ -~

CabotandCrabtree 1915 1 155 87 56 51 1 29 ...

24 I "' 1 .' Brongersma . . 1924 100 100 36

Twinem . . 1937 1 252 1 115 28 21 ... ... Oppenheimer . 1937

Hamilton Stewart . 1952

Pyrah . . . 1953

Sutherland . . 1954

Total Duration of ~

Recurrence Follow-up Percentage (years)

_ _ _ _ _ _ _ _ _ _ ~

... ...

... 5 1 (minimum) I

... ... (ipsilalteral)

169 141 53 1 24 I ... 1 ... ... 4 , I (average)

(average) ... ... 1 6 . 8 1 ... 6 4

21 ... ... 5 to 20 " I

101 87

156 156 60 35

240 240 63 47 ~ 37 , ... ... ' 8.4 I I I (average) ~

Baker and Connelly 1956 357 ... ... l . . . I . . . ... I I

Comparison of Reported Post-operative Recurrence Rates.-Different investigators have reported wide variation in recurrence after operation. Sutherland (1954) demonstrated that several factors were involved including the percentage of patients re-examined, thoroughness of investigation, duration of follow-up, and distinction between true and false recurrence.

1 . Percentage of Patients Re-examined.-Many recurrent calculi are symptomless and questionnaire follow-up is not reliable. Ideally all patients should be traced, questioned, and re-examined, but this has seldom been possible.

2. Investigation.-Thorough assessment requires that the patient is interviewed and at least an X-ray of the renal tract obtained and a specimen of urine examined microscopically and bacteriologically.

3. Duration of Follow-up.-Few writers have stated clearly the duration of follow-up. Oppenheimer (1937) appreciated the importance of this factor, and while he followed his own series for an average of four years, he thought that a ten-year or fifteen-year period would give more accurate results. Hamilton Stewart (1952) followed his patients for an average of 6.4 years after partial nephrectomy and excluded patients on whom he had operated within the previous

41 8 B R I T I S H J O U R N A L O F U R O L O G Y

two years. Sutherland’s (1957) series of 974 patients had an average follow-up of 8.4 years, and Pyrah (1953) collected cases where operation had been performed five to twenty years previously.

4. True and False Recurrence.-The distinction between true recurrence in which new calculi are formed, and false recurrence in which stones or portions of stone have been left behind at operation, can be made only if an X-ray was taken at operation or shortly afterwards. Repeated X-rays should follow at regular intervals. In this way false recurrence will be recognised and the formation of fresh symptomless calculi detected.

Other factors, of less importance, also contribute to the variation in reported recurrence. Many series have been too small for comparison of results ; the marked geographical distribution of urolithiasis may affect recurrence rates in different parts of the world, and in recent years improved diagnostic methods, surgical techniques, and antibiotics should help to reduce the incidence of recurrence.

In any retrospective survey valuable information has been lost or not recorded. The ideal survey is a prospective one, with a series of patients fully investigated and followed ten or twenty years into the future with regular re-examination and X-ray.

METHOD OF PRESENT SURVEY

Criteria.-All patients included in this survey had a history of calcium-containing upper urinary tract stone for a minimum period of ten years. Patients with uric acid and cystine stone were excluded.

Source of Material.-During the years 1951 to 1961,20,000 patients attended the Department of Urology in Leeds. There were 1,725 patients with upper urinary tract stone and from them were surveyed 538 patients who had a minimum ten-year history of stone. All patients had comprehensive case notes and X-rays available and had attended at out-patient clinics in recent years. The patients in this survey were a selected series in that they were taken from the records of a urological department of a teaching hospital and may not represent the problem of recurrent urinary stone in the population as a whole. However, the information needed for assessment can only be obtained in sufficient quantity from the well-documented records of such a department.

Method of Review and Investigation.-Of the 538 patients, 309 (57 per cent.) were interviewed personally. Patients who had failed to attend in recent years numbered 229, though all had adequate case notes and X-rays and a history of stone for ten years prior to their last attendance. Of these, fifty-two patients (10 per cent. of total) were traced but were unable to attend because of distance, age, or infirmity. A questionnaire reply from patient or general practitioner was accepted in this small group because the presence or absence of recurrence at their last attendance was known and any error introduced would be minimal. The remaining 177 patients (33 per cent.) could not be traced and were included only up to the time of their last attendance at hospital.

At interview a detailed case history was obtained, noting the chronological order of stones passed or removed surgically and the side of the urinary tract affected. Particular reference was made to the onset of urolithiasis and to previous urinary tract disease. Relevant information about occupations, pregnancies, family history of stone, and time spent overseas was recorded, along with a history of indigestion or peptic ulcer, bone or joint disease, or periods of prolonged recumbency.

All patients had a plain renal tract X-ray and a urine specimen examined for cells and organisms, either at their last attendance or at interview. Only the fifty-two patients traced but not interviewed had a short period not covered by X-ray. Further investigations, both radiological and biochemical, were arranged if indicated.

UPPER U R I N A R Y T R A C T S T O N E 419

Analysis of Case Histories.-The clinical history was broken into separate units called " incidents," each incident representing a stone or group of stones. An analysis of the case history was obtained by listing the incidents in chronological order, marking which side of the renal tract was affected and classifying them as spontaneous passage, surgical operation, or X-ray diagnosis of stone. In this way stone formation and recurrence could be followed in each upper renal tract separately.

Most " incidents " were clear-cut episodes of symptoms followed by the passage or removal of a stone, but occasional difficulties presented. Repeated bouts of colic over a considerable period of time produced by a known calculus were counted as one incident only and classified as its eventual outcome (e.g., operative removal), while a short bout of colic followed by a shower of calculi from a known group of calculi was also regarded as one incident.

The first patient started with a stone on the left side which was passed spontaneously. Six years later ureterolithotomy was done for a recurrence on the same side. His next incident was in 1955, was on the opposite side of the renal tract, and nephrolithotomy was performed. Lastly, in 1960 another stone was found in the left kidney on X-ray-this stone is still present as the patient refuses treatment. Similarly, the second patient started with a staghorn calculus and nephrectomy was performed. Nine years later and again the following year he passed a stone spontaneously. When last seen he was free from calculi.

Two examples are shown (Fig. I ) .

Name No.

I I 1 Side Passed Year ~ -~ - 1 Spon- I X-ray

~ Left ~ Right ~ taneous'y l N . 1 U . I

J. S. ~ 1 2 3

A. P. I 2

... ... I ... 1945 I + i ... + 1951 ~ + I ... 1 ... ... 1 ... -t 1955 + ... ... ...

+ 1 1960 + ... ... K - R T . ~ ... ...

~ 1959 + 1 i- ... ... 1 . .

... ... I .'. 1 9 4 9 i + ~ i 1 ... ... . . . . . . . l . . . l . . . 1958 ...

+

~~~

Operat ion

I ... ... + I ... ... I ::: 1 ... ... 1

* K-RT signifies a stone present in the kidney on X-ray for which the patient refuses treatment.

FIG. 1 Analysis of case history.

Results have been calculated from an analysis of stones made for every patient. When details were available of time and side affected, an accurate pattern of stone formation was made. About 5 per cent. of patients produced many stones in rapid succession, and it was difficult to form an accurate case history ; most of these patients were included in the Unclassified Group described later.

Classification of Incidents.-All incidents of stone in the patient's history were classified as spontaneous passage, surgical operation, or X-ray diagnosis.

1. Spontaneous passage was accepted if the patient had seen or recovered the stone, or if it had been seen on a previous X-ray.

2. Surgical Operations. - These were described as nephrolithotomy, ureterolithotomy, pyelolithotomy, partial nephrectomy, and nephrectomy. On twenty-nine occasions calculi were removed from two separate sites in the urinary tract at one operation; these were classified as the operation considered to be more important.

420 B R I T I S H J O U R N A L O F U R O L O G Y

3. X-ray Diagnosis.-This group comprised stones identified by X-ray and still present at the patient's last attendance. Most calculi in this group were small and produced minimal symptoms. Others needed surgical removal but either the patient refused treatment or intercurrent disease was present. Lastly, in some patients, small scattered calculi were present and surgical removal was not possible.

RESULTS

Duration of Survey (Fig. 2).-The survey extended from the onset of symptoms of stone until the date of the patient's last attendance (or reply to questionnaire) and therefore in some patients included a short period of time during which they had stone symptoms before diagnosis. The minimum history was ten years and the mean for all patients was 18-5 years. Addition of the

periods of survey for all patients totalled 9,925 years and 20 per cent. of the patients had a history longer than twenty-five years.

DURATION OF HISTORY PATENTS

(1°1

n r

10 I5 20 hIl 25

MEAN 18.5 YEARS Distribution of Incidents.-The survey included MALES 358 1,949 incidents of stone for 538 patients. FEMALES 180 1. Spontaneous passage of stone accounted

for 1,209 incidents (62 per cent.). On fifty-one occasions the passage of the stone had been assisted by some form of transurethral instru- mentation, e.g., ureteral meatotomy, ureteric dilatation, etc. I t was impossible to assess the value of these manoeuvres.

2. Surgical operation for removal of stone JO 35 40+ had been performed 554 times (28 per cent.) and the

n u YEARS frequency of operations used is shown in Table 11.

FIG. 2 3. X-ray diagnosis of stone accounted for 186 incidents (9.5 per cent.), eight of which were

ureteric stones and thc remainder renal stones. Of the 186 incidents, 125 were small calculi with minimal, if any, symptoms ; for twenty-seven incidents intercurrent disease prevented surgical removal, while seventeen patients were advised operation but refused ; lastly, on seventeen occasions multiple small calculi, not suitable for surgical removal, were present.

TABLE I1 Analysis of 554 Operations for Upper Urinary Tract Stone

performed on 358 Males and 180 Females

..,.... Nephrolitholomy . Pyelolithotomy . . Ureterolithotomy . Partial nephrectomy . Nephrectomy .

134

I48

101 52 '

I - I

84 50 62 57

I I7 31 35 17 46 55

I -~ ~~

Total . 554 344 210 ~

Rtiological Factors.-The significance of local factors (Randall and Perry, 1937) and general factors (Butt, 1952; Howard, 1962) has been emphasised, while Grossman (1938) and Chapman

U P P E R U R I N A R Y T R A C T S T O N E 42 1

(1946) pointed out that a single cause of stone formation probably did not exist. Multiple factors acting independently or together may be responsible, and even these may alter during the stone-forming years of the patient's !ife. The atiological factors in this series are shown in Table 111. In a small number of patients stone formation was secondary to an anatomical abnormality in the urinary tract, to prolonged recumbency, and to hyperparathyroidism ; most of these patients had recurrent calculi. Apart from a small Unclassified Group, the remaining idiopathic patients were separated into those with only a single stone during the survey and those with recurrent stones. Infection, present to some extent in all groups, will be discussed separately. Other contributory factors were associated bone disease, the onset of stone during pregnancy, and a family history of urolithiasis.

TABLE 111

Etiology of Stone Formation in 538 Patients ~ ~ ~ ~~ _ _ ~

Females ' Total ~ Single Recurrent ~ Ma,es 1 Number Stone Stones

~

Etiology I- Anatomical abnormality ,

Recumbency . Hyperparathyroidism . Idiopathic with single stone . Idiopathic with recurrent stones . Unclassified . .

Total .

24 14 10

129 339 22

538 _ _

8 2 0

I29

0 ...

16 12 10

339 22

...

139 399

14 10 12 2

64 1 65 249 1 90

15 7

4 1 6

358 I80

Anatomical Abnormality.-A gross urinary tract abnormality producing stasis was present in twenty-four patients (4.5 per cent.) and may have been missed in others if the lesion had progressed to destroy the kidney and hide the original abnormality. The commonest abnormality was hydronephrosis which was present in thirteen patients and was due to an aberrant renal artery in five patients, ureteric achalasia in four patients, and was unexplained in four patients. Other abnormalities were polycystic disease of the kidneys (three patients), horseshoe kidney (three patients), and a bifid urinary tract (two patients). Congenital bladder-neck obstruction, medullary sponge kidney, and a non-rotated kidney accounted for the remaining three patients. Hunner (1928) suggested that stasis, particularly following ureteric stricture, was an important factor in stone formation. Barney (1922) found only five patients (horseshoe kidney, three ; aberrant renal artery, two) in his review of seventy patients and Sutherland (1954) only three patients (horseshoe kidney, two ; pelvi-ureteric stenosis, one) in 21 6 patients.

Recumbency.-A prolonged period of recumbency preceded the onset of urolithiasis in fourteen subjects. Fractures of pelvic girdle and lower limbs were responsible in nine patients, often as a result of war injuries. Chronic bone and joint disease such as tuberculosis, ankylosing spondylitis, and rheumatoid arthritis was present in five patients.

Hyperparathyroidism.-Hyperparathyroidism produced stone in ten patients, all of whom had a parathyroid adenoma or hyperplasia removed surgically and confirmed histologically. A negative exploration of neck had been performed on three of these patients at some previous time. Urinary tract stone had been present in these patients for an average of thirteen years before successful parathyroidectomy, and one patient had produced recurrent calculi over twenty-six years.

Idiopathic.-The remaining patients, with the exception of the Unclassified Group, were rzgarded as idiopathic in that there was no proven atiology, though a few were affected by some of the associated factors described later. The idiopathic stone-forming patients were separated

422 BRITISH J O U R N A L O F UROLOGY

into 129 patients with a single calculus, and 339 patients with recurrent calculi. Included in the latter group are eight patients with biochemical evidence suggesting hyperparathyroidism, but the patients refused exploration of the neck and the diagnosis remained unproven.

Unclussijed.-The patients in the Unclassified Group differed from the majority in that their kidneys were seldom, if ever, free from calculi which they passed spontaneously at short intervals. All had eight or more separate incidents of stone, and it was difficult to analyse their case histories accurately. Patients described as nephrocalcinosis numbered five, of whom three had renal tubular acidosis. Chronic urinary infection was present in four patients, another was diagnosed as familial hyperoxaluria, and no cause was found in the remainder.

Associated Factors.-Factors which may have been associated with stone formation were examined (Table IV). Out of 180 women surveyed, the onset of stone occurred during pregnancy, usually with pyelitis, in thirteen patients (7.2 per cent.). A history of prolonged alkali therapy for peptic ulcer was given by twenty-two patients (4.1 per cent.) and a family history of urolithiasis was obtained from twenty-one patients (3.9 per cent.). Sutherland ( 1 954) reported similar results, associating stone formation with pyelitis of pregnancy in 16 per cent. (sixteen out of ninety-eight women examined), with peptic ulcer in 3-7 per cent. and with a family history of the disease in 6 per cent. Apart from bone and joint disease producing recumbency calculi or the bone changes found in hyperparathyroidism, ten patients had advanced bone and joint disease. Paget’s disease was present in four patients and rickets in two patients ; three patients suffered from arthritis and one from ankylosing spondylitis. Inadequate fluid intake may have been responsible in six patients who started forming stones while in the tropics and in five who laboured in a hot atmosphere. Previous trauma to the kidney was reported by only two patients. The relationships of hypercalciuria and urinary infection to stone formation are discussed later.

TABLE IV

Associated Factors in Stone Formation A. Pregnancy . . . . . . . 13 B. Pepticulcer . . . . . . . 22 C. Family history . . . . . . . 21 D. Bone disease . . . . . . . 1 0 E. Onset in tropics . . . . . . 6 F. Occupation . . . . . . . 5

H. Hypercalciuria . . . . . . . . . . I. Urinary infection . . . . . . . . .

G . Trauma . . . . . . . . 2

Comparison of Single and Recurrent Idiopathic Stone-forming Patients (Table V).-The group of patients with a single stone had an equal sex ratio with sixty-four males and sixty-five females. Out of 129 incidents of stone thirty-six (28 per cent.) were stones passed spontaneously, four (3 per cent.) were diagnosed on X-ray, and eighty-nine (69 per cent.) were removed by operation. There was a high incidence of nephrectomy which accounted for thirty-three of the eighty-nine operations (37 per cent.) while only sixteen calculi entered the ureter and were removed by ureterolithotomy (18 per cent.). By comparison, the 339 patients with idiopathic recurrent stone formation comprised 249 males and ninety females, a ratio of 2.8 : 1. Incidents of stone totalled 1,243 of which 733 (59 per cent.) were stones passed spontaneously, 137 ( I I per cent.) were diagnosed on X-ray, and 373 (30 per cent.) were removed by operation. Nephrectomy was performed on fifty-two occasions (14 per cent. of operations) and 105 calculi were removed by ureterolithotomy (28 per cent. of operations). Comparison of these single and recurrent stone-forming patients showed that recurrent stone formation occurred more frequently in males, and that usually small calculi were formed, capable of passing spontaneously or entering and

U P P E R U R I N A R Y T R A C T S T O N E 423

impacting in the ureter. On the other hand, patients with a single stone had a higher incidence of operative removal, especially nephrectomy, and spontaneous passage of a calculus was relatively infrequent. Sutherland (1 954) reviewed recurrence after 240 operations for stone and found that 50.7 per cent. of operations on males recurred and only 24 per cent. of operations on females ; he pointed out that this occurred even though urinary infection was commoner in women and that urinary stasis was often present during pregnancy. It is shown later in this survey that chronic urinary infection was present in 18 per cent. of the idiopathic recurrent stone-forming group, and if present in the single-stone group was associated with another pathological process. Single and recurrent stone-forming patients differed in sex ratio, in the incidence of spontaneous passage and operation, and in their relationship to chronic infection. These factors suggest that different retiological factors may be involved in these groups.

TABLE V

Comparison of Clinical Features between Single and Recurrent Idiopathic Stone-forming Patients

Idiopathic (Single Stone)

, I ' Total number . . 129

i Ratio males/fernales . I 1 : I

Total incidents of stone . Spontaneous passage . X-ray diagnosis . Operation .

Total operations . Nephrolithotomy . Pyelolithotomy . Ureterolithotomy . Partial nephrectomy . Nephrectomy .

129 36 4

89

89 13 18 16 9

33

i Idiopathic (Recurrent Stone)

339 2.8: 1

1,243 133

::: ~

313 96 90

105 30 52

Sex and Side Incidence.-Sex (see Table III).-There were 358 males and 180 females in the survey, a ratio of 2 : 1. Other investigators have noted the higher proportion of males : Twinem (1937), 5 : 3 ; Grossman (1938), 4 : 1 ; Winsbury-White (1946), 3 : 2 ; while Sutherland (1954) found the sexes to be almost equally represented with a ratio of 6 : 5.

In this investigation the high proportion of males with recumbency calculi was related to the occupational liability of the male to severe trauma. It is known that women have a higher incidence of hyperparathyroidism than men : this applied in the present survey but the numbers were too small for significance. The marked difference in sex ratio between the idiopathic patients with a single stone and those with recurrent stones has been discussed, the single stone-forming patients being equally distributed between the sexes while patients with recurrent stone had a male/female ratio of 2.8 : 1 .

The sex distribution of the various operations might be expected to follow the overall sex ratio of two males to one female. However, this ratio applied only to partial nephrectomy (see Table 11). Nephrolithotomy had a higher incidence among women than was expected, and pyelolithotomy even more so. Ureterolithotomy was predominantly an operation of males, especially among idiopathic recurrent stone-forming patients, in which eighty-six ureterolithotomy operations were done on men and only nineteen on women. By comparison, nephrectomy


performed on women outnumbered those on men, particularly among idiopathic patients with a single stone (twenty-two women, eleven men). The total number of stones passed spontaneously was 1,209, of which 893 (74 per cent.) were passed by men and 316 (26 per cent.) by women, a sex ratio of 3 : 1. Out of 1,237 incidents related to males (893 stones passed and 344 removed by operation) the stone passed through the ureter or was removed from it on 1,010 occasions (82 per cent.) whereas of 526 incidents in females (316 stones passed and 210 removed by operation) spontaneous passage or ureterolithotomy accounted for only 347 (66 per cent.). These observations, along with the higher incidence of ureterolithotomy in men, suggested that males produced small calculi, many of which were passed or at least were small enough to enter the ureter, while in women calculi were larger when the patient first attended, producing a high incidence of pyelolithotomy and even nephrectomy. This survey confirmed the increased liability to stone formation and recurrence in the male.

Side.-The initial stone in the case history occurred on the right side in 255 patients (47 per cent.) and on the left side in 246 (46 per cent.) ; thirty-seven patients (7 per cent.) had bilateral calculi at first attendance. There were 1,949 incidents of stone in the survey, of which 900 were on the right side and 1,049 on the left. However, the increased incidence of stone on the left side was produced by two patients in the Unclassified Group, one of whom had passed more than seventy calculi from the left and the other more than thirty calculi. When these two patients were excluded, stone occurred on the right side in 900 (49 per cent.) and on the left side in 949 incidents (5 I per cent.).

The complete series of 538 patients showed that stone affected the right side only in 159 (29.6 per cent.), the left side only in 154 (28.6 per cent.) and both sides (though not necessarily at the same time) in 225 patients (41.8 per cent.). When patients with single stone were excluded, the incidence of bilateral stones rose to 56 per cent. Thirty-seven patients (7 per cent.) had bilateral calculi when they first attended hospital and had no clinical history to suggest that one or other side had been affected first. The remaining patients, initially unilateral who became bilateral, did so in an average time of twelve years. Twinem (1937) and Winsbury-White (1946) calculated that stone was commoner on the left side and the latter suggested that this was due to the proximity of the left urinary tract to the perivenous lymphatics draining genital tract infections. However, Swift Joly (1929) and Sutherland (1954) found no marked difference in the frequency with which the sides were affected. Reports on the incidence of bilateral stone have varied from 8 per cent. (Baker and Connelly, 1956) to 30 per cent. (Hellstrom, 1938). The high incidence of 42 per cent. found in this series was related to the prolonged period of follow-up, for ten years or longer were taken by more than half of those patients who developeda contralateral stone during the survey.

The Onset of Stone Formation.-Age (Fig. 3).-Age was calculated from the date of onset of symptoms which could be attributed to urinary tract stone. The commonest age of onset was in the age groups 20 to 29 and 30 to 39, which included two-thirds of all patients. The high incidence in these two decades was largely due to males, for in females onset was evenly spread from 20 to 49 years of age. The average age of onset was slightly later for women than men, an observation already made by Sutherland (1954), and in the age group 20 to 29 years the proportion of men to women was 5 : 2.

Type.-Almost one-half of all patients surveyed (248 patients, 46 per cent.) had the first calculus in their case history removed by surgical operation. In 275 patients (51 per cent.) the first calculus was passed spontaneously, in eight patients a stone diagnosed radiologically was still present at last attendance, and in seven patients the exact onset was uncertain.

Duration of Symptoms.-An estimate was made of the duration of symptoms attributable to stone preceding the patient’s first attendance. Patients were excluded if accurate information was not available. Symptoms preceding the passage of a stone at the start of the clinical history were obtained in 241 patients and of these 77 per cent. passed the stone within a month of the

UPPER U R I N A R Y T R A C T STONE 425

onset of symptoms. Hellstrom (1949) reported that 70 per cent. of his patients who passed a stone did so within four weeks of the onset of symptoms. The first stone incident in 176 patients was treated by operation and of these 28 per cent. reported symptoms for less than a year, 56 per cent. from one to five years, and 16 per cent. for more than five years. Sutherland (1954)

160-

120-

80-

40-

reported values of 23.5, 46.6, and 30.9 per cent. respectively for the same duration of symptoms preceding operation for stone.

Infection in Stone Formation and Recur- rence.-The part played by urinary infection at the onset of urolithiasis is difficult to assess in a retrospective survey. Some patients did not attend hospital at the time of the first calculus, while others attended but either urine for bacteriological examination was not collected or the result was misplaced. In- fection may be introduced by cystoscopy or operative removal of stone, and often the pattern of infection was obscured by urinary antiseptics and antibiotics given both by hosuital staff and the patient’s own practitioner.

538 PATIENTS

WITIENTS 2007

AGE AT ONSET OF SYMPTOMS

019 10/19 2N9 3019 40f49 50159 aOh9 lQ+ YEARS

FIG. 3

* Method-This survey assessed the relationship of urinary infection to stone formation by examining the case records and bacteriological reports of all patients. There were insufficient data in eighty-seven patients. A total of 1,384 bacteriological reports on urine was examined for the remaining 45 I patients. Each patient was classified as :-

I. No Infection.-All urine samples had been sterile on culture or grew contaminants only. 2. Occasional 1nfecrion.-These patients had an intermittent or occasional infection at some

Often this infection was associated with the time in their history of urolithiasis. presence of a stone and cleared with its spontaneous passage or removal.

3. Chronic Infection.-A persistent infection was present over many years.

Results: (1) Incidence ofZnfection.-Of 451 patients examined 66 per cent. had no urinary infection, 17 per cent. had infection at some time, and 17 per cent. had chronic infection (Table VI).

Idiopathic single and recurrent stone-forming patients showed no infection in 69 per cent. of both groups. Occasional infection was present in 23 per cent. of the single-stone patients, but on every occasion it cleared with the spontaneous passage or removal of the stone, and subsequent urines were sterile. Likewise, 13 per cent. of recurrent stone-formers had occasional infection and, in thirty-four of the thirty-nine patients concerned, this was associated with the presence of a calculus and cleared with its removal. Chronic urinary infection was present in nine of the single-stone patients but this was secondary to another lesion in the urinary tract with only one exception ; three patients had a severe urethral stricture, two had a staghorn calculus and refused treatment, two had disease of the contralateral kidney, one suffered from chronic cystitis in a neurogenic bladder, and in the remaining patient no other lesion was found. By comparison, chronic infection was present in 18 per cent. of patients with recurrent calculi and more than half of them had severe renal damage (chronic pyelonephritis or hydronephrosis) often accompanied by renal failure. Repeated courses of antibiotics and urinary antiseptics made little impression on the chronic infection suffered by these patients. Although most patients with single or recurrent idiopathic stones had sterile urine, when chronic infection was present, it was usually associated with recurrent stones.

(2) Organisms (Table VII).-Of the 148 patients who had occasional or chronic urinary 4 G


infection B. coli was the predominant organism cultured in 116 (78 per cent.), Proteus vulgaris predominated in nineteen patients (1 3 per cent.), and staphylococci, Str. fRcalis, or Ps.pyocyaneus were cultured in the remainder. Infection with mixed organisms, usually B. coli and Proteus vulgaris, was present in thirty-six patients (24 per cent.).

Occasional Jnfection

TABLE VI Urinary Infection Associated with Urolithiasis in 45 1 Patients

Chronic Infection

~~

~ _ _ Idiopathic with single stone . Idiopathic with recurrent stones . Anatomical abnormality . . Recumbency stone . . Hyperparathyroidism . . Unclassified patients . . .

~ -~ ~-

All patients . . . . ~- ~

Number of Patients

106

282

21

13

10

19

45 1

No Infection

73 (6904)

194 (69 %)

(56 %) 9 t 81

12 7 1 -- ~

303 (66%)

Predominant Organism cultured in 148 Patients with Urinary Infection and Stone

I Organism I Patients 1 Percentage

~~~~ ~

B. coli . . . Proteus vulgaris . . Staphylococci . . Str. fecalis . . . Ps. pyocyaneus . Mixed infection . .

~~

116 19 10 2 I

36

78 13 7

l 2 24

~ ~~

Discussion.-Most writers have agreed that infection plays an important part in recurrence of stone, but there is still disagreement about its relationship to original stone formation. Brongersma (1924) and Oppenheimer (1937) both reported recurrence in only 12 to 17 per cent. of patients with sterile urine compared with 33 to 35 per cent. in the presence of infected urine. Hellstrom (1949) detected ipsilateral recurrence in 46 per cent. of patients with infected urine and Sutherland (1954) found recurrence in 64 per cent. In this survey when chronic infection was present it was usually associated with recurrent calculi, but the surprising fact that emerged was the high proportion (69 per cent.) of idiopathic single and recurrent stone-forming patients who had sterile urine at all times. Most of these patients were treated during the era of antibiotics which may be partly responsible for the low incidence of chronic infection. When infection was

U P P E R U R I N A R Y T R A C T STONE 427

associated with the presence of a stone and cleared with its removal, it usually did so without antibiotics. These results suggest that urinary infection is not now a major factor in stone formation, though it may be responsible for some cases of recurrent stone.

Biochemical Findings.-Hyperparathyroidism.-Out of 538 patients, ten were diagnosed as hyperparathyroidism and eight other patients refused parathyroidectomy, though biochemical evidence supported this diagnosis. Only patients with stone formation for ten years were included so this does not represent the true incidence, which has been variously reported from 0.7 per cent. (Nordin, 1962) to 17 per cent. (McGeown, 1961). Hodgkinson and Edwards (1963) estimated the incidence of hyperparathyroidism in this region to be 2.2 per cent. of all patients with renal and ureteric stone, and 5 per cent. of those with recurrent stone. They reviewed the literature and discussed the possible explanations for wide variation in reported incidences.

TABLE VIII

Relationship between Stone Incidence and Hypercalciuria

Number of Incidents

Normal

I 1 : 4

5 6 or more

I

~~~ ~

~

Number of Subjects

258

35 66 36 30 23 52

Percentage with H ypercalciuria

8 *

23 29 50 50 61 25

* Hodgkinson, A., and Pyrah, L. N. (1958). Brir. J . Surg., 46, 10.

Hyperca1ciuria.-Male patients with twenty-four-hour urine calcium output in excess of 300 mg. and female patients in excess of 250 mg. were regarded as hypercalciuric. Urinary calcium estimations were available for 289 patients of whom 161 patients were within the normal range, and 107 patients showed hypercalciuria. The majority of patients with hypercalciuria had recurrent calculi, but this result was biased by the tendency of the surgeon to request urinary calcium measurement in patients with recurrent calculi. It had been measured in only one-quarter of patients with a single stone compared with three-quarters of those with four or more incidents of stone. However, when patients with chronic infection, gross impairment of renal function, and primary hyperparathyroidism were omitted, a relationship was seen between stone incidence and hypercalciuria (Table VIII).l Hypercalciuria was present in 8 per cent. of 258 normal subjects examined by Hodgkinson and Pyrah (1958). In this survey the incidence of hypercalciuria rose from 23 per cent. for patients with a single stone to 61 per cent. for those with five incidents of stone. For six and more incidents of stone there was a marked fall in the incidence of hypercalciuria. These results suggest that, to a certain extent, hypercalciuria is related to the incidence of stone recurrence, but this does not apply to patients who have developed six or more stones. Most of the latter patients were included in the aetiological Unclassified Group as they were observed clinically to follow a different pattern from the majority. Melick and Henneman (1958) found hypercalciuria in 68 out of 207 consecutive patients attending a stone clinic, an incidence of 33 per cent. Anderson, Hodgkinson, and

These results were calculated from urinary calcium measurements made by Dr A. Hodgkinson, M.R.C., Metabolic Disturbances in Surgery Research Unit, The General Infirmary, Leeds.


Pyrah (1 96 1) examined the relationship between urinary calcium excretion, renal calcification, and formation of calculi, and from observations on patients with calcium-containing renal stones they concluded that hypercalciuria was a contributory factor but that other factors. were also involved.

Stone Composition.-Chemical analysis was available for only 181 calculi out of the 1,949 stones in the survey. Calcium oxalate predominated in 103 calculi (57 Der cent.). calcium

160 -

40-

80 -

0 -

I20 -

phosphate in thirty-eight (i 1 per cent.), mixed oxalate and phosphate in twenty-eight (1 5 per WMBER OF NJClDENTS PER PATIENT

IPs9 lNCIDENTS (2 per cent.). No conclusions can be drawn from these results for the composition of the original calculus was known in only a few patients and more care was taken to ensure analysis of calculi from patients with recurrent than with single calculi. Twinem (1937) thought that recurrence was more probable with phosphate than with oxalate stones. Hellstram (1938) stressed that traces of am-

538 PATiENTS

8 .ciu,,i,

RECURRENCE

Recurrence Rate.-Incidents of stone totalled 1,949 for 538 patients, an average of 3.6 incidents per patient. The histogram (Fig. 4) shows that two incidents had the highest frequency. The sexes were equally represented at one incident (sixty-eight males and seventy-one females) but thereafter the proportion of males rose with increasing number of incidents. During the period of survey 399 patients out of 538 had more than one calculus, a recurrence rate of 75 per cent., and it was higher for males (80 per cent.) than for females (60 per cent.). This represents recurrence in patients followed for an average of 18.5 years ; if this period was extended the recurrence rate would increase as some patients with a single stone developed recurrence.

Burkland and Rosenberg (1955) made a questionnaire survey of urolithiasis throughout the United States of America and reported an average recurrence rate of 14 per cent. Other investigators stated that 90 per cent. of patients with one renal calculus never develop another (Baker and Connelly, 1956) and that 85 per cent. of patients have only a single small stone which is passed spontaneously (Garvey and Boyce, 1956). Prince and Scardino (1960) found in patients with ureteric calculi that 15 per cent. had a previous history of calculous disease and 8.8 per cent. developed a recurrence. The high recurrence rate found in the present survey is supported by

UPPER U R I N A R Y TRACT STONE 429

the results of post-operative recurrence produced by Oppenheimer (1 937) and Sutherland (1954) in long-term surveys. It is apparent that the incidence of recurrence depends on the duration of follow-up and the care with which the patients have been assessed.

The First Recurrence.-Time Interval.-The case histories of 399 patients with recurrent calculi were examined for the time interval between the onset of symptoms (or diagnosis) of the initial stone and the same for the first recurrence, either ipsilateral or contralateral. Initial and first recurrent calculi which were passed spontaneously, removed by operation, or diagnosed radiologically were included. The average interval found was 9.5 years and the distribution is shown in Table IX. Recurrence had occurred in less than one year in fifty-four patients (14 per cent.) of whom thirty-seven had bilateral calculi at first attendance, ten recurred within a few weeks, and the remainder during the year. Only 42 per cent. of patients recurred in less than five years and 20 per cent. were fifteen years or more. No significant difference was found in the time interval between patients in whom the first stone was passed spontaneously and those in whom it was removed surgically. Braasch (1917) thought that two years was the usual interval between operation and recurrence and HellstrBm (1938) found that half the patients in his staphylococcal stone series recurred within one year. The results of the present survey show that false recurrence rates are obtained if the duration of follow-up is inadequate.

TABLE IX

Time Interval between Initial Stone and First Recurrence in 399 Patients

~ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ -

I

i

Time Interval Number of (Years) Patients

________ Less than 1 . 54

I I4 13

I t o 4 . 5 t o 9 .

15 to 19 . 41 20 to 24 . 24

10

' I

10 to 14 . . I " 17

. . I 2 5 - .

~~

Total Percentage

14 42 61 80 92 98 I00

Ipsilateral and Contralateral.-The first recurrent stone was on the same side of the urinary tract as the initial calculus in 58 per cent. of 399 patients with recurrent calculi, on the opposite side in 28 per cent., bilateral calculi were present at first attendance in 12 per cent., and there was insufficient information in 2 per cent. Addition of patients with contralateral first recurrence and those with bilateral calculi at first attendance demonstrated that 40 per cent. of patients had stones on both sides of the urinary tract by their first recurrence. Eventually 56 per cent. of this group of patients had bilateral calculi.

True and False Recurrence.-It is important to distinguish between true recurrence, in which new calculi are formed, and false recurrence due to a portion of stone not passed or left behind at operation. This distinction can only be made by radiological examination soon after the passage of a stone or in the immediate post-operative period. In this survey note was taken of all incidents of stone in which there was satisfactory evidence that following spontaneous passage or operation there were no residual calculi in the ipsilateral urinary tract ; doubtful radiological opacities were classified as residual calculi. Out of the 1,949 incidents in the survey, 798 (41 per cent.) were free from residual calculi, 453 following spontaneous passage, and 345 after operative removal of a stone. For the remainder there was either insufficient information, residual calculi

430 B R I T I S H J O U R N A L OF UROLOGY

were present, or nephrectomy made ipsilateral recurrence impossible. Of the 453 incidents of spontaneous passage following which the affected side of the urinary tract was known to be free from calculi, a true ipsilateral recurrence followed 237 (52 per cent.). The average interval for this recurrence was 8.4 years ; this compared with 9-5 years already calculated as the average interval between the initial stone and the first recurrence.

POST-OPERATIVE RECURRENCE

Definition.-In this investigation recurrence was calculated for those operations followed by another stone, either ipsilateral or contralateral, which was passed spontaneously, removed surgically, or demonstrated by X-ray. A calculus present in the contralateral urinary tract at the time of operation and subsequently passed or removed was not counted as a recurrence. These criteria follow those of other published data (Oppenheimer, 1937 ; Sutherland, 1954) and the results are suitable for comparison. True ipsilateral recurrence and true contralateral recurrence are discussed separately. For the purpose of this investigation nephrolithotomy, pyelolithotomy, and ureterolithotomy are described collectively as conservative operations and partial nephrectomy and nephrectomy as radical operations.

Types of Operation Performed.-The 554 operative procedures used in this series are shown in Table 11. In addition, there were eighteen occasions when operative treatment was advised and refused and another twenty-seven occasions when removal of a stone was prevented by intercurrent disease. Five conservative operations were followed at an early date by nephrectomy (two for pyonephrosis, two for secondary hremorrhage, and one for a non-functioning kidney) : these operations were excluded from calculation of recurrence. At least one surgical operation was performed on 70 per cent. of all patients during the period of survey and 22 per cent. had 111 ul tiple operations.

Duration of Post-operative Follow-up.-The duration of follow-up was the time interval from the date of operation until the patient's last attendance, and the mean duration showed the time during which a particular group of operations was exposed to post-operative recurrence. Partial nephrectomy, practised with increasing frequency in recent years, had a shorter average follow-up than established conservative operations. Hamilton Stewart (1952) and Sutherland (1954) excluded patients on whom operation took place within two years, but this was not done in the present study. The average post-operative follow-up, recurrence, and average interval until recurrence were calculated for 398 conservative operations (Table X).

TABLE X

Recurrence after 398 Conservative Operations

~ Number Operation

Average 1 Recurrence

(Years) (Percentage) Follow-up ~ Number

Nephrolithotomy 133

Pyelolithotomy . I I7

Ureterolithotomy . ~ 148 I

14.9

11.8

9.5

92 (69 per cent.)

66 156 per cent.)

81 ( 5 5 per cent.)

Average Time Interval I

(Years) '

7. I

5.6

5.9

U P P E R U R I N A R Y TRACT S T O N E 43 1

Recurrence after Conservative Operations.-The average period of follow-up was longer for nephrolithotomy (14.9 years) than for pyelolithotomy (1 1.8 years) or ureterolithotomy (9.5 years), and 50 per cent. of nephrolithotomy operations were followed for fifteen years or more compared with 30 per cent. for pyelolithotomy and 20 per cent. for ureterolithotomy. This longer follow-up reflects the higher incidence of nephrolithotomy performed during the earlier years of stone formation in patients with a long history ; in recent years pyelolithotomy and partiai nephrectomy have been preferred to nephrolithotomy. Hellstrom (1949) and Sutherland (1954) also observed the decreasing popularity of nephrolithotomy.

In agreement with the results of other investigators, nephrolithotomy had the highest recurrence rate, and 92 operations (69 per cent.) developed a recurrence out of 133 operations performed. After 1 17 pyelolithotomy and 148 ureterolithotomy operations another stone was found in sixty-six (56 per cent.) and eighty-one (55 per cent.) respectively. These high recurrence rates were due to the detection of late recurrence by prolonged follow-up. The average interval between operation and the recurrent stone was 7.1 years after nephrolithotomy, 5.6 years after pyelolithotomy, and 5.9 years following ureterolithotomy. Only half of the patients who developed recurrent calculi did so in less than five years (Table XI) and the proportion appearing ten years or more after the operation varied from 18 to 28 per cent. Thus it is not surprising that the incidence of recurrence reported here is higher than that of other series with a shorter follow-up (see Table I). Sutherland (1954) found a similar high incidence of recurrence, of which 58.4 per cent. appeared within five years and 87.6 per cent. within ten years. Oppenheimer (1937) also reported a high recurrence rate (58.5 per cent.) after nephrolithotomy. At the other extreme, Baker and Connelly (1956) stated that the likelihood of recurrence after the spontaneous passage or removal of a stone was about 9 per cent., that recurrence usually appeared in three to five years and was infrequent after eight years. A similar survey by Reddy (1960) reached the same conclusions. Prince and Scardino (1960) found that 15 per cent. of patients with ureteric calculi gave a previous history of calculous disease and 8.8 per cent. developed a recurrence. The factors responsible for the wide variations in reported series have been discussed.

TABLE XI

Time Interval until Post-operative Recurrence after 239 Conservative Operations

Percentage Recurrence in

Operation

Nephrolithotomy .

Recurrence Less than Five to Nine Ten Years ' Five Years ~ Years ~ or More

92 ~ 54 ~ 28

1 Pyelolilhotomy . 66 1 50 , 27 23 I

Ureterolithotomy . 1 81 63 17

Immediate Results of Conservative Operations.-Before the incidence of true ipsilateral recurrence could be calculated, the proportion of conservative operations following which the ipsilateral upper urinary tract was free from calculi was obtained. Operations performed on patients in the Unclassified Group were excluded from this result and from calculation of true ipsilateral and contralateral recurrence as these patients differed from the majority of stone- forming patients and were rarely free from calculi. Table XI1 shows that all ipsilateral calculi


were removed by 80 to 84 per cent. of conservative operations. Residual calculi were usually left by design rather than accident, e.g., ureterolithotomy invariably removed the ureteric stone, but in 17 per cent. of these operations residual calculi were present in the kidney.

Operation

TABLE XI1

Immediate Results of 370 Conservative Operations

Total Number

Pyelolithotomy . . Ureterolithotomy .

116

133

~~

Ipsilateral Urinary Tract '

~-

~ Nephrolithotomy . Pyelolithotomy . Ureterolithotomy .

+ee from Calculi

97 (80 per cent.)

97 (84 per cent.)

110 (83 per cent.)

97

97

110

Residual Calcu

(43 per cent.)

(33 per cent.) 37 1 6.4

24 (20 per cent.)

19 (16 per cent.)

23 (17 per cent.)

~-~ - ~~

116

True Ipsilateral Recurrence (Table XIII).-The incidence of true ipsilateral recurrence was obtained for those operations which were known to have removed all calculi from the ipsilateral upper urinary tract. Operations with residual calculi, which could produce false recurrence, were excluded. A true ipsilateral recurrence developed after 50 per cent. of nephrolithotomy, 43 per cent. of pyelotithotomy, and 33 per cent. of ureterolithotomy operations. The average intervals between operation and recurrence were 10.9, 7.7, and 6.4 years respectively.

TABLE XI11

True Ipsilateral and Contralateral Recurrence following Conservative Operations

I I I

Total Available I Operation

~

Total Ipsilateral Interval Recurrence (Years) True I Average

49 I 10.9 I 121 (50 per cent.) I 7.7

42 I 134

True Contralateral Recurrence

39 (32 per cent.)

31

I Average ' Interval (Years)

11.5 ~

8.8 (23 per cent.)

32 1 7.2 , 1311 ~ P F rent 1

True Contralateral Recurrence (Table XIII).-The outcome of a calculus present on the opposite side at the time of operation was disregarded and only fresh contralateral stone formation was accepted as recurrence. True contralateral recurrence followed thirty-nine times after 121 nephrolithotomy (32 per cent.), thirty-one times after 134 pyelolithotomy (23 per cent.), and thirty-two times after I16 ureterolithotomy operations (28 per cent.), at average intervals of 11.5, 8.8, and 7-2 years respectively. Again the prolonged follow-up showed a higher incidence than previous reports : Oppenheimer (1937) reported contralateral recurrence after 15 per cent., and Sutherland (1954) after 12 per cent. of conservative operations with prolonged follow-up. Twinem (1937) did not state the duration of follow-up, but he concluded that local factors were


responsible for recurrence as he found only 2 to 3 per cent. contralateral recurrence. In this survey the incidence of true contralateral recurrence was not as high as true ipsilateral recurrence and the average interval following operation was slightly longer, thus confirming the suggestion of Hellstrom (1938). In the widely varied opinions and recurrence rates offered by many investigators, all have agreed that nephrolithotomy has the highest incidence of post-operative recurrence. Surprisingly in this study nephrolithotomy also had the highest incidence of contralateral recurrence. This may have occurred because of the longer follow-up available or, alternatively, because general factors which affect both kidneys produced the type and situation of stone for which this operation was performed.

Passed Spontaneously

Residual Post-operative Calculi.-Calculi remaining in the ipsilateral urinary tract after operation may produce false recurrence. In this series the majority of residual calculi were small and situated elsewhere in the urinary tract, away from the site of operation ; usually they were left by design rather than accident. Out of sixty-six calculi not removed by conservative surgery (Table XIV) eighteen (27 per cent.) were subsequently passed spontaneously, thirty-one (47 per cent.) were removed by another operation, and seventeen (26 per cent.) were still present on X-ray at the patient’s last attendance. The forty-nine calculi passed or surgically removed represented false recurrence after 370 conservative operations, an incidence of 13 per cent. If calculi still present radiologically were included, the incidence rose to 18 per cent. Wide variations in the incidence of false recurrence have been reported; 4.5 per cent. (Braasch, 1917). 23 per cent. (Oppenheimer, 1937), and 30 to 40 per cent. (Nay, 1928).

I Operative Position Removal 1 Unchanged

TABLE XIV

Analysis of the Outcome of Residual Post-operative Calculi

Nephrolithotomy . Pyelolithotomy . . Ureterolithotomy .

Operation ~ Number

24

19

23

18 (27 per cent.)

Total . 66 31 1 17 (47 per cent.) (26 per cent.)

~~~~ ~~

4

7 l 3 I 7

7 5 i 4 1 1 3 1 6

Recurrence following Partial Nephrectomy.-In this survey only fifty-two partial nephrectomies had been done, usually in recent years, and the average follow-up was shorter for this operation than the established conservative procedures. The incidence of true ipsilateral recurrence was the most satisfactory measure of the success of partial nephrectomy. In this series out of fifty-two partial nephrectomies five were excluded as unsuitable, one had nephrectomy for secondary hzmorrhage, two died soon after operation from unrelated causes, and two still had stones elsewhere on that side. The remaining forty-seven operations were followed for an average of 5.8 years, during which time true ipsilateral recurrence developed seven times (15 per cent.) in an average interval of 4.1 years (Table XV). The follow-up for seven operations was only one year, and if these were excluded the recurrence rate increased to 17 per cent. True contralateral recurrence followed 34 per cent. of partial nephrectomies, a value similar to that found for nephrolithotomy. Of the seven patients who developed an ipsilateral recurrence, six of them also had contralateral recurrence. The significant proportion of late recurrence


after conservative operations has been emphasised in this survey, and the shorter follow-up with a small number of partial nephrectomies makes comparison difficult. Recurrence may increase with the passage of time, but at present the results are encouraging. Stewart (1952) found recurrence in only 6.8 per cent. of eighty-seven patients carefully re-examined and with an average follow-up of 6.4 years.

I

...

TABLE XV

Recurrence after Partial Nephrectomy and Nephrectomy

4.1 16

...

~

Partial nephrectomy

Nephrectomy . 101 I 13.3

I I ~~ ~

True Ipsilateral Recurrence Recurrence

Interval (Years)

~~

3.1

7.7

Recurrence following Nephrectomy.-In most cases of upper urinary tract stone clinical factors clearly determine whether or not nephrectomy should be performed. Between the extremes there are borderline cases for which nephrectomy was often advised because of the high recurrence rate for conservative operations and the belief that contralateral recurrence was rare after nephrectomy. Brongersma (1924) found contralateral recurrence in only I a 5 per cent. of patients and advocated primary nephrectomy for unilateral stone accompanied by infection. This result was supported by Twinem (1937) with 4 per cent. contralateral recurrence, but an incidence of 11 per cent. was reported by HellstrBm (1933) and Sutherland (1954), and 15 per cent. by Oppenheimer (1937). In the present study recurrence on the opposite side followed thirty-four times after 101 nephrectomies (34 per cent.) with an average interval of 7.7 years (Table XV). This is almost the same incidence of contralateral recurrence as was found for partial nephrectomy and for nephrolithotomy. It is in agreement with the results of Cahill ( 1935) who studied 377 patients with calculous anuria and found that nephrectomy had been performed on 128 (34 per cent.). The considerable incidence of contralateral recurrence should be taken into account when there is doubt regarding the necessity for nephrectomy.

DISCUSSION

The results of this survey show a high incidence of recurrence following both the spontaneous passage and the operative removal of stone. They contradict the report of Garvey and Boyce (1956) who stated that about 85 per cent. of patients have a single small stone which is passed spontaneously, and of Baker and Connelly (1956) that 90 per cent. of patients with one renal calculus never develop another. In this survey 75 per cent. of the patients did develop another stone and 70 per cent. had a surgical operation for stone at some time in the case history. Most writers have calculated post-operative recurrence only and have compared their results with previously published work, but few have stated clearly the duration of follow-up and the percentage of patients re-examined, the two most important factors which give wide variation in results. The results of Sutherland (1954, 1957) and of this investigation do not support the suggestion of Baker and Connelly (1956) and Reddy (1960) that there has been a progressive decrease in the incidence of bilateral and recurrent calculi from the high incidence reported by Cabot and Crabtree (1915). The treatment of the individual stone has improved with better

U P P E R U R I N A R Y T R A C T STONE 435

surgical techniques, diagnostic methods, and antibiotics, but in spite of intensive research the underlying cause is still active in most patients. It is hardly surprising that recurrence is frequent.

Analysis of case histories in this investigation depended on clinical assessment. Undoubtedly errors have been introduced. Some patients described as having only a single calculus may have had another one either symptomless or misdiagnosed, while other patients regarded as recurrent stone-formers will have had only a single calculus which presented as two clinical episodes. Every attempt has been made to avoid these errors, and for 95 per cent. of patients a case history of satisfactory accuracy has been obtained.

Melick and Henneman (1958) claimed that a cause can be found in about 50 per cent. of patients with upper urinary tract stone. This depends on what is accepted as a cause of stone formation and what is regarded as an associated factor of uncertain import. In this investigation the aetiological factors of urinary tract abnormality, recumbency, and hyperparathyroidism accounted for only 9 per cent. of the patients, but if the associated factors with chronic urinary infection and hypercalciuria are included, then an explanation can be offered for stone formation in 46 per cent. of the patients.

Most investigators have examined the problem of post-operative recurrence and little attention has been given to the patients who did not recur. The difference in case histories between patients with a single stone and those with recurrent stone suggests that different retiological factors affect those two groups and that patients with a single stone are not simply those who have yet to develop recurrence. It may be that single-stone formation is produced by local causes and that recurrent stone is more frequently associated with general aetiological factors giving the high incidence of bilateral stone formation and of contralateral post-operative recurrence. Most patients with recurrence had two, three, or four episodes of stone formation often with long periods of freedom between them. Patients who formed eight or more calculi were collected as an Unclassified Group in this study and most had more than twenty recurrent calculi. On X-ray they were seldom free from calculi, both kidneys were usually affected, and operation was performed to remove only a specific stone which produced acute symptoms. The incidence of hypercalciuria was low in this group, though in other patients it had an increased incidence with each recurrence. Chronic infection affected only four of the twenty-two patients in this group and five others were diagnosed nephrocalcinosis. Intensive investigation found no abnormality in the remainder, and it is suggested that the atiological factors in this group of patients may be different from those in most patients with recurrent calculi.

This long-term follow-up shows the magnitude of the problem of stone recurrence which was often delayed five years and, not infrequently, ten years or more with long periods of freedom from stone formation between the episodes. Consequently the success of any medical regimen or operative measure to reduce the incidence of recurrence cannot be assessed on a short-term follow-up. Although this study has been called a " long-term " follow-up it has surveyed an average of 18.5 years only, a fraction of the stone-forming years of most patients. Extension of the study would probably show an even higher incidence of recurrence.

The incidence of post-operative recurrence is high. Pyelolithotomy is to be preferred to nephrolithotomy, and the results of Hamilton Stewart (1952) and of this study justify partial nephrectomy in suitable cases. Contralateral recurrence was as frequent after partial nephrectomy and nephrectomy as it was following the conservative operations, thus healthy renal tissue should be conserved whenever possible. Residual calculi, left in the ipsilateral urinary tract, were often removed at a later operation. The possibility of secondary operation should stimulate the surgeon to consider their removal a t the primary procedure. Probably ureterolithotomy and partial nephrectomy should be combined more frequently. The importance of careful removal of all calculi, with the help of X-ray control on the operating table, has been shown.

All patients with upper urinary tract stone should have measurement of serum and urinary calcium and phosphorus concentrations ; hyperparathyroidism is not uncommon and probably

436 BRITISH JOURNAL OF U R O L O G Y

is responsible for 5 per cent. of patients with recurrent stone. Every attempt should be made to eradicate urinary infection, and in this survey all patients with chronic urinary infection developed recurrent calculi apart from a few in whom infection was associated with another pathological condition in the urinary tract. However, chronic urinary infection was not a major factor in stone formation and recurrence.

Unfortunately stone composition was not known in a sufficient number of patients to consider each composition separately in relation to the clinical history and laboratory results. All calcium-containing stones have been treated as one entity in this review yet the varying compositions represent different aetiological factors. Information of greater value would be obtained from a prospective survey with full clinical and metabolic investigations on a smaller number of patients.

Late and sometimes symptomless recurrences stress the importance of prolonged follow-up for patients with upper urinary tract stone, more especially for those who have undergone operation. The benefit of a continued high fluid intake should be explained to the patient as it is the one simple prophylactic measure which is likely to be successful. Regular radiological and metabolic investigations should be obtained, for this series has demonstrated ten patients with hyperparathyroidism who had urinary tract stone for an average of thirteen years before diagnosis and treatment by parathyroidectomy.

For most patients urinary tract stone is a recurrent disease, frequently affecting both renal tracts and often involving the patient in operative treatment. Grossman (1938) stated, “ The atiology of urinary lithiasis is not one problem nor is it the sum of several problems, but a series of different problems.” Twenty-five years of research since then have shown how large is the series of different problems.

SUMMARY

I . A survey of 538 patients with upper urinary tract stone for a minimum of ten years and an average of 18.5 years was undertaken. Adequate case notes and X-rays were available, and 90 per cent. of the patients had been currently assessed by radiological and clinical examination. The case histories were analysed to obtain the pattern of stone formation and recurrence in both upper urinary tracts. Episodes of stone total 1,949, of which spontaneous passage accounts for 62 per cent., operative removal for 28 per cent., and I0 per cent. are stones still present on X-ray.

2. The aetiological and associated factors are described along with the side, sex, and age incidences. Both sides of the urinary tract are affected equally and 42 per cent. of patients have bilateral calculi ; the sexes are equally distributed among patients with one stone, but males predominated among patients with recurrent stones ; the most frequent age of onset is the age group 20 to 29 years. Patients with a single stone show considerable differences from those with recurrent stone formation. In 9 per cent. of patients calculi are due to an anatomical abnormality, recumbe.ncy, or hyperparathyroidism.

3. In 51 per cent. of patients the first stone is passed spontaneously, usually within one month of the onset of symptoms. The first stone is removed by operation in 46 per cent. of patients.

4. Chronic urinary infection is present in only 17 per cent. of patients and is not a major factor in stone formation. However, most patients with chronic infection have recurrent stones.

5. The incidence of hypercalciuria is proportional to the frequency of stone formation. Chemical analysis of calculi shows 57 per cent. calcium oxalate, 21 per cent. calcium phosphate, and 15 per cent. mixed oxalate phosphate.

6. There is a high incidence of recurrent stone formation, 80 per cent. for males, and 60 per cent. for females. The prolonged follow-up shows a high proportion of late recurrences and the average interval until the first recurrence is 9.5 years.

7. Post-operative recurrence is assessed for 554 operations. Recurrence follows 69 per cent. of nephrolithotomy, 56 per cent. of pyelolithotomy, and 55 per cent. of ureterolithotomy


operations. The average intervals until recurrence develops are 7.1, 5.6, and 5.9 years respectively. True ipsilateral and contralateral recurrence is also assessed.

8. Of stones left in the urinary tract after operation, 27 per cent. are passed spontaneously, 47 per cent. are removed by another operation, and 26 per cent. remain in situ.

9. Ipsilateral recurrence followed 15 per cent. of partial nephrectomies and contralateral recurrence 34 per cent. of nephrectomies.

10. The reasons for the high recurrence rates found are the prolonged follow-up and the strict standard of reassessment.

I thank Professor L. N. Pyrah and Mr F. P. Raper for their encouragement and advice and for permission to study their patients. I am grateful to Professor A. S. Johnstone and his staff for radiological investigations, and I am indebted to Miss E. Earnshaw for her help in tracing patients, organising clinics, and for typing the manuscript.

REFERENCES

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LONG-TERM SURVEY OF 538 PATIENTS WITH UPPER URINARY TRACT STONE