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operation, all have had virtually a full range of painlessmovement of their backs, and have been aware of noweakness.

SUMMARY

1. The pathology of the intervertebral disc is dis-cussed in its relation to sciatica, and it is submittedthat most cases of " ordinary sciatica " are due tolessions of the intervertebral disc.

2. Thirty cases are reviewed in the light of symp-tomatology and findings at operation. In twenty-eight of these, changes in the intervertebral disc wereresponsible for the sciatica.

3. While many cases of sciatica recover unaided,in others operative treatment is called for. Theindications for and results of the operation are

discussed.

My thanks are due to Prof. Hugh Cairns for hisadvice and assistance in the preparation of thisreport; and to the members of the staff of the Rad-cliffe Infirmary for their cooperation in assemblingthe clinical material.

REFERENCES

Garland, L. H. and Morrissey, E. J. (1940) Surg. Gynec. Obstet.70, 196.

Love, J. G. (1939a) J. Amer. med. Ass. 113, 2029.— (1939b) Proc. R. Soc. Med. 32, 1697.

Mixter, W. J. and Barr, J. S. (1934) New Engl. J. Med. 211, 210.

CARCINOMATOSIS OF BONE

DIFFICULTIES IN DIAGNOSIS

BY A. M. G. CAMPBELL, D.M.Oxfd, M.R.C.P.HON. PHYSICIAN TO THE ROYAL BRINE BATHS CLINIC, DROITWICH ;CLINICAL ASSISTANT AT THE ROYAL HOSPITAL, WOLVERHAMPTON

MANY cases diagnosed as chronic rheumatism areexamples of other diseases. The 7 patients whosehistories are given here were first diagnosed as havingrheumatism, but in all of them the pain was causedby secondary carcinomatous deposits from a primarygrowth which had not caused any symptoms.

METASTATIC CARCINOMA IN BONE

There is evidence that the spread of tumour cellsto bone is by the blood rather than by the lymphatics.The bones involved are not necessarily those in closeproximity to the primary growth but those whichcontain the most red marrow, such as the ribs,sternum, vertebrae, and proximal ends of the longbones. Joll (1923) quotes figures from the CancerHospital which give a ratio of 34 metastases in bonefrom cancer of the breast to 1 from cancer of theprostate. This gives a false impression of the incidenceof metastases in bone due to carcinoma of the prostate.Joll also mentions that metastases in bone fromcarcinoma of the oesophagus are not so rare as iscommonly thought. The order of frequency in whichbones were involved were vertebre, ribs, sternum,skull, femur, humerus, and pelvis. In his opiniontrauma is a predisposing factor, but this is question-able. Secondary carcinomata in bones are not rare,especially when the primary growth is in the breast,prostate, thyroid, lung, kidney (hypernephromata),stomach, tongue, oesophagus, or suprarenal. Thefollowing cases illustrate some of these points.

CASE-RECORDS

CASE 1.—A draughtsman, aged 60, was admittedto the General Hospital, Birmingham, under Dr.T. T. Hardy, complaining of loss of weight andweakness, on Dec. 5, 1937. About a year previouslyhe was losing weight, but medical examinationrevealed nothing wrong. In October, 1937, he began

to feel out of sorts but had no pain or indigestion,although he had lost his appetite and just beforeadmission had vomited once. He attributed his lossof weight to worry about his work.

Examination on admission revealed an obvious lossof weight but no physical signs to explain it. A blood-count showed a definite microcytic anaemia : red cells3,660,000, haemoglobin 68 per cent., colour-index0-9, and white cells 8200. A differential count ofthe white cells was normal.No koilonychia was observed. A test-meal showed

achlorhydria, but administration of histamine pro-duced a small flow of acid. Radiograms of thestomach, duodenum, and sinuses were normal.A simple iron-deficiency anaemia was diagnosed,although this did not explain the loss of weight,which was attributed to worry. The patient wasdischarged on Jan. 12, 1938.

During the next six months he continued to loseweight. He only took iron for about a month, andthree months after his discharge he began to havesevere pain in his left thigh and lumbar region.This he took to be " rheumatism," for which he triedvarious proprietary remedies without success. InJuly, 1938, he was sent to Droitwich with " rheu-matism."He first came to me on July 20, 1938, complaining

of an intense and continuous pain in the region of thefifth lumbar vertebra. He was extremely weak, andeasily became dyspnoeic on exertion. There was anexcessive pallor of his visible mucosae, and a loudsystolic bruit was heard all over the praecordium.He had a severe anaemia, and the result of a blood-count was as follows :-

The red cells showed little variation in size butwere hypochromic. No nucleated red cells were seen.The average diameter was 7 ft. These findings led meto diagnose carcinomatous deposits in bone, and theloss of appetite suggested that the primary growthwas gastric.The patient was immediately transferred to the

General Hospital again under Dr. Hardy. Thediagnosis was partially confirmed by radiographicevidence of a secondary deposit of growth in the fifthlumbar vertebra and a confirmation of the blood-picture. He developed a swinging temperature, andjust before his death, which took place on Sept. 10,became incontinent. An unsuccessful effort was madeto try and locate the primary growth before death.Radiograms of the chest and skull were normal, andtests for occult blood gave negative results.At necropsy the primary growth was discovered

to be a large annular carcinoma of the lower end of theoesophagus. Secondary deposits were found in thepericesophageal glands, the left femur, and the fifthlumbar vertebra, whose arch had been destroyed bythe growth, which was pressing on the cauda equina.Histological sections of the femur showed an invasionby a squamous-celled new growth.

CASE 2.-An engineers’ fitter, aged 57, was admittedto Guy’s Hospital on June 28, 1935, for constantsevere pain in both thighs for the previous eightmonths. Apart from pleurisy at 30 he had been afit man until December, 1934, when he noticed a dullpain in his right leg, which was persistent,

" nagging,"and more troublesome in bed. Loss of sleep and thispain made him consult his doctor in January, 1935.He was admitted to Worcester Infirmary, whereclinical and radiographic examination revealed nocause for his pain, which was thought to be rheumatic.He was treated with a vaccine and radiant heat. InMay a similar pain affected the right leg, and he wassent into Guy’s Hospital for investigation.On examination he was thin and looked ansemic.

He walked with difficulty and was very weak. Hisloss of weight, since his pain began had been abouta stone. His heart was slightly enlarged. Both

778

sacroiliac joints were tender on palpation. No tendonreflexes could be elicited in his lower limbs, but thiswas discovered many years ago when he reported formilitary service. No other neurological signs werefound, and, the Wassermann reaction being negative,no definite cause for the absence of these reflexeswas found. The prostate was enlarged and hard.Radiograms suggested either secondary carcino-matosis or Paget’s disease in the left femur and pelvicbones. The skull and tibiae were normal. A blood-count gave the following results -

No abnormal red cells were found, although theiraverage diameter was high. On the evidence of theradiograms and the blood-count secondary carcino-matosis of bone was diagnosed. This was confirmedwhen the patient developed signs of a malignantprostate about a month later. He died in October,1935.

CASE 3.-A cooper, aged 58, was admitted to Guy’sHospital in July, 1937, for pain in the low back andright thigh, which had been provisionally diagnosedby his doctor as osteo-arthritis of the right hip-joint.His story was that in April, 1937, his right foot becamehot, swollen, and painful, and he was sent to theLondon Hospital. Synovitis was diagnosed, and aftertwo weeks off work he was able to get about again ;but in May he began to have severe stabbing pain inthe region of his fifth lumbar vertebra ; this painvaried in severity and at times was absent. Latterlyopium derivatives were the only thing which relievedit. For a week before admission the pain had in-volved the right thigh also. Since the onset of thepain there had been a loss of 1 t st. in weight.On examination there was general wasting, which

affected especially the muscles of the lower limbs.The mucous membranes were pale. The prostatewas enlarged and firm but not unduly so. Movementof the hip-joints was free and painless, but slight painwas felt on pressure over the sacro-iliac joints. Theurine and cerebrospinal fluid were normal. TheWassermann reaction was negative. A test-mealshowed achlorhydria. Tests for occult blood gavenegative results. Radiograms of the alimentary tractwere normal. Radiograms of the pelvis and lumbarvertebrae were normal, apart from slight osteo-arthritic changes in both sacro-iliac joints. A blood-count gave the following results :-

The red cells showed anisocytosis, poikilocytosis,and polychromasia, with 2 per cent. of reticulocytes,many normoblasts, and 150,000 platelets. Thisanaemia,, with a moderately high colour-index and thepresence of abnormal red and white cells, indicatedsome stimulation of the marrow, and the most likelycause was carcinomatosis of bone. Re-examinationof the prostate suggested that it might be malignant.The patient was discharged in the middle of August

to be given deep X-ray therapy as an outpatient.He rapidly got worse and had to be readmitted inOctober, 1937, with continuous pain. There wasradiographic evidence of metastases in the sacrum,ribs, and the fourth and fifth lumbar vertebrae. Theblood-picture showed even more primitive cells, andthe patient continued to lose ground despite deepX-ray therapy. He eventually discharged himselffrom hospital and died a month later. The primarygrowth was most probably prostatic, but this couldnot be confirmed, because there was no necropsy.

CASE 4.-An unemployed man, aged 54, was

admitted to the Royal Hospital, Wolverhampton,

under Dr. J. H. Sheldon in August, 1938, complainingof pain in the low back of three months’ duration.His doctor had diagnosed this pain as rheumatic.The pain was not persistent but was very severeduring the attacks. The patient had lost 2 st. inweight and had had some dyspnoea on exertion.A month before admission he had had some difficultyin starting to micturate, and the stream was poor.On examination he was extremely thin. The

lumbar spine was tender on pressure. The prostatewas enlarged, hard, and irregular, and radiogramsrevealed extensive carcinomatous metastases in theribs, dorsal and lumbar vertebrae, and pelvis. Ablood-count gave the following results :-

No abnormal cells were seen. The cerebrospinalfluid was normal and the Wassermann reaction wasnegative.The foregoing case is much more definite than those

previously recorded, but it is interesting to note thenormality of the blood-picture despite extensivedeposits. The following three cases are recorded morebriefly. The patients were all sent to Droitwich ascases of rheumatism.

CASE 5.-An engineer, aged 5-1, was first seen inJanuary, 1938, complaining of pain in the chest,thighs, and low back. He had had paratyphoid in1924 but otherwise had been healthy until, six monthsbefore coming to Droitwich, he had noticed increasinglassitude and loss of weight. Over this period he hadlost 2 st. The pain had begun in October, 1937,and gradually had increased in severity. He describedit as deep-seated and gnawing.On examination he was anaemic and wasted. There

was tenderness on pressure over his sixth and seventhribs in the axillary line. The base of the right lungwas dull to percussion, and air entry was poor. Onrectal examination the prostate was enlarged, hard,and irregular. Radiograms of the dorsal and lumbarvertebrae, ribs, pelvis, and femur showed them to befull of carcinomatous metastases. A blood-countshowed 2,500,000 red cells, 8500 white cells, andhaemoglobin 62 per cent. No abnormal red or whitecells were found. The patient was sent for deepX-ray therapy but died in September, 1938.

CASE 6.-A married woman, aged 60, was seen inApril, 1938, complaining of intense pain localisedto a small area in the lumbar region. She had a longhistory of vague pains and was obese, highly-strung,and apprehensive. She first began to have pain inNovember, 1937, and had been radiographed thenwithout any abnormality being found. In January,1938, she first complained of an intense local painabout in. external to the right sacro-iliac joint.Her doctor suspected malignancy, and she wasexamined by a London consultant, who could findno abnormality and diagnosed a localised fibrositis.

I first saw her with Dr. J-.W.T. Patterson in April, 1938.Her pain had become so severe that she was confinedto bed and needed morphia. Her appetite was good,and she had not lost weight. There was no ansemia.,and neither Dr. Patterson nor I could find physicalsigns of organic disease. Radiograms of the lumbarspine and pelvis were normal. We formed the opinionthat the case was largely functional, and this wassupported by a surgical opinion from Birmingham.

: About May 10, however, the patient complained ofnumbness in the right leg. An extensor plantarreflex and a slight sensory loss were found. She wassent home and afterwards seen by Dr. G. Riddoch, who

þ found a paraplegia and sensory loss below the twelfthE thoracic segment, probably due to bony carcino-

matosis from an undetected primary growth pressingon the spinal cord. The patient became incontinentand died on June 30, 1938. No necropsy was done.

This case is an instructive example of the diffi-

, culties in diagnosing secondary deposits in bone, for

779

despite careful clinical and radiographic examinationin March, 1938, showing no obvious abnormality, thispatient was dead by July, 1938. It emphasises thedanger of diagnosing any unexplained pain as

functional.

CASE 7.-A farmer, aged 75, was sent to Droitwichin June, 1939, because of gnawing pain in the lumbarand cervical region, which had been diagnosed as

fibrositis. Until March, 1939, he had been remarkablyfit; then he had begun to have pain in the lumbarand cervical region. This pain was gnawing and deep-seated, and the patient got no relief from commonremedies for rheumatism. It was unrelated to move-ment and periodic, but the bouts were becoming morefrequent. His appetite had failed, and he had losta stone in weight and noted increasing weakness andfatigue, which he ascribed to his age.On examination he was very thin, and there was

definite tenderness over the fourth and fifth cervicalvertebrm on deep pressure, but movement of the neckdid not produce the pain. The prostate was enlargedhard, and irregular. Radiograms revealed secondarycarcinomatous deposits in the bodies of the fourthand fifth cervical vertebrae. Examination of theblood showed a hypochromic anaemia with no abnormalred or white cells. The haemoglobin was 65 per cent.and the colour-index 081. The patient died twomonths later with symptoms of prostatic obstruction.

COMMENTS

These 7 cases were first diagnosed as rheumatism,but in each of them the pain was really due to asecondary carcinomatous deposit. The correct diag-nosis depends on the pain, the blood-picture, and theradiograms.Pain.-Most patients present themselves because

of pain. The character of this pain is often gnawing,deep-seated, intense, and usually unrelated to move-ment. It may be difficult to control with the simpleanalgesics used to relieve rheumatic pains. In somecases the bones are tender on pressure, as in case 7.Local applications, heat, and physiotherapy tend tomake it worse. Freedom of the articular movements

may suggest that the joint is not osteo-arthritic.Fibrositis should never be diagnosed in the absenceof painful nodules. The pain in fibrositis is oftensevere in the early mornings but works off with move-ment as the day progresses, unlike the spasmodic orcontinuous pain caused by malignant disease.Blood-picture.-This may be normal, or there may

be either hypochromic anemia or myelogenous (leuco-erythroblastic) anæmia. Case 4 supplies an exampleof a normal blood-picture with no great anaemia,despite extensive secondary deposits. Recently therewas a patient in the Royal Hospital, Wolverhampton,who was initially diagnosed mistakenly as a case ofPaget’s disease, largely because of absence of anaemiaand of general signs of malignancy and because theradiograms did not reveal the true condition. Furtherobservation, however, proved that there was

carcinomatosis of the bone secondary to a primarygrowth of the prostate.Hypochromic anaemia is probably the commonest

type found. In case 1 hypochromic anaemia wasdiagnosed nine months before there was any paindue to deposits in bone. There was no evidence of a

primary growth, and, although at necropsy an

(Bsophageal growth was found, occult blood had neverbeen found in the stools. It is most probable thatthis anaemia was due to toxic depression of the bone-marrow. Before death the picture changed to thatof leuco-erythroblastic anaemia.Leuco-erythroblastic anœmia.—From the point of

view of diagnosis this picture is the most helpful.The clarification of our views on blood changes

associated with several diseases of bone is due chieflyto Piney (1922) and Vaughan (1934). The anaemia

may not be severe, but it is characterised by thepresence of immature red and white cells, a variablecolour-index, and a low platelet count. Such a

picture is not confined to carcinomatosis of bone butis also seen in multiple myelomatosis, myelosclerosis,marble-bone disease of Albers-Schonberg, Cooley’serythroblastic anaemia, and aleukaemic myelogenousleukaemia, but the commonest cause is undoubtedlycarcinomatosis of bone. The anaemia is not related tothe secondary destruction or the crowding out of themarrow. Small malignant deposits may produce achange in the blood-picture even without radiologicalevidence, as in case 3, whereas extensive deposits maycause no blood changes. In a case of mine with second-

ary deposits in bone from a carcinoma of the breast theblood-picture in June showed a hypochromic ansemia,whereas in September myelocytes 1-5 per cent. werefound, with numerous normoblasts. Lucey (1939)published a case in which this condition of the bloodwas mistaken for pernicious anaemia and then acho-luric jaundice. In pernicious anaemia immaturewhite cells are rare (Lucey said that myelocytes4 per cent. were present) ; this finding, with lack ofresponse to liver therapy, is against the diagnosisof pernicious anaemia. Only in a crisis can acholuricjaundice simulate leuco-erythroblastic anaemia, andLucey’s case, which showed an increased fragility ofthe red cells and a positive indirect van den Bergh,must be exceptional. He admits, however, that thecells were not typically globular. His case is of

importance in showing that carcinomatosis of bonemay simulate a haemolytic anaemia. Lucey mentionsalso the improvement of his patient after blood-transfusion. This is not unusual in anaemia of thistype; Robin (1935), reporting a case, said: "Adiagnosis of carcinomatosis of bone-marrow secondaryto a recurrence in the stomach of an ulcer becomingmalignant was made, but was revised, due to theabsence of recognisable bony deposits, the favourableresponse to blood transfusion, and the failure to have aprimary growth." The cases reported here show thatthese features may be absent in carcinomatosis.Confusion may also be caused by idiopathic steat-orrhcea, in which failure to absorb the essentialfactors may lead to a macrocytic or a microcyticanaemia resembling the leuco-erythroblastic type.The steatorrhcea should establish the diagnosis.The anaemia, therefore, varies both in type and indegree but may be of early diagnostic importance andis due rather to toxic irritation of the bone-marrowthan to destruction of haemopoietic tissue.

Radiology is the most important aid to diagnosisin most cases ; but in some, as in case 3 and case 6,the radiological signs are late. The changes due tosecondary deposits from carcinoma of the prostateare osteoplastic, as opposed to osteolytic changes dueto those from a breast carcinoma. As regards theosteolytic cystic area, the differential diagnosis ofdiffuse osteitis fibrosa cystica due to parathyroidtumour may have to be considered, but the pain andnormal calcium preclude this diagnosis. Paget’sdisease must be considered in connexion with osteo-plastic deposits. The course is longer and relativelypainless in Paget’s disease, which is unlike carcino-matosis. From a purely radiological point of viewthe diagnosis may be difficult, but Brailsford (1938)points out " that the detection of isolated areas ofdestruction of the peripheral bony outline and can-cellous trabeculae, and the recognition that the in-creased density is not due to coarsened fused trabe-culae but a deposition of calcium within the cancellous

780

mesh, indicate the malignancy of the lesion." Healso says that in some deposits from scirrhouscarcinoma of the stomach differentiation may bealmost impossible.

In carcinomatosis of bone several other diagnosticpoints are of value. There are often the generalsigns of malignancy, such as wasting, loss of appetite,and pyrexia. Pathological fracture of a bone may bethe first sign of a deposit in that bone. Metastasisin a vertebra may cause pressure on the spinal cord ;in case 7 an extensor plantar reflex was one of the fewphysical signs.My purpose has been to show that secondary car-

cinomata of bone may be wrongly diagnosed as

rheumatism, owing largely to the failure to demon-strate a primary growth. Although a correct diag-nosis does not allow any hope of cure, it does save thepatient unnecessary expense and waste of time

undergoing physiotherapy ; further, the conditioncan be at least alleviated by deep X-ray therapy.Any physician working in a spa must be careful not tooverlook such cases. The difficulties of diagnosismay be considerable, and, as in these few cases, theremay be both normal radiograms and a normal blood-picture in carcinomatosis. Where there is the slightestsuspicion of malignant disease it is worth repeatingthese examinations more than once.

SUMMARY

In 7 cases of carcinomatosis of bone, the initialdiagnosis was rheumatism. The chief criteria indiagnosis are pain, anæmia, and radiological findings.It is suggested that, if the condition is suspected, thecase should be observed for a prolonged period despitenegative early findings in the blood or the radiograms.My thanks are due to Dr. T. T. Hardy, of Birming-

ham, for the use of his notes on case 1, and Dr. J. H.Sheldon, of Wolverhampton, for permission to

investigate case 4. I am also indebted to the lateDr. E. P. Poulton for permission to report the casesfrom Guy’s Hospital.

REFERENCES

Brailsford, J. F. (1938) Brit. J. Radiol. 11, 507.Joll, C. F. (1923) Brit. J. Surg. 11, 38.Lucey, H. C. (1939) Lancet, 2, 76.Piney, A. (1922) Brit. J. Surg. 10, 235.Robin, I. G. (1935) Guy’s Hosp. Rep. 85, 163.Vaughan, J. (1934) The Anæmias, London.

BLOOD VISCOSITY IN CARDIACFAILURE

ITS MODIFICATION BY ADMINISTRATION OF CALCIUM

GLUCONATE

BY ALFRED S. ROGEN, M.B. Glasg., F.R.F.P.S.

(From the University Department of Materia Medicaand Therapeutics and Stobhill Hospital, Glasgow)

THE viscosity of the blood is an important factor indetermining the amount of work to be done by theheart in maintaining the circulation through the peri-pheral vessels. Any decrease in blood viscositylightens the strain on the heart, and this may be ofconsiderable importance when there is cardiac weak-ness. Markson (1936),1 reporting investigations on 26patients with heart-failure, said that in the presenceof signs and symptoms of congestion there was anincrease in the viscosity of the blood, and that thiswas reduced as recovery took place. When cedemawas severe, he found low values for blood viscosity,which rose as diuresis increased.

1. Markson, A. Glasg. med. J. 1936, 125, 201.

During an investigation on the influence of calciumgluconate on the various manifestations of cardiacfailure, I determined the range of blood viscosity invarious clinical types to discover whether the intra-venous administration of calcium gluconate had anyeffect on it.

TABLE I-BLOOD VISCOSITY IN CARDIAC FAILURE

BLOOD VISCOSITY IN CARDIAC FAILURE

The blood viscosity was determined with the Hessviscosimeter in 35 patients with cardiac failure, in50 people in whom no subjective or objective evidenceof heart-disease was obtained, and in 20 healthypeople. In all cases the determination was madewhen the subject was in the postabsorptive state.The average blood viscosity in the 20 healthy subjectswas 4-5 (5-4-4-0), whereas in the group of patientswith some condition other than cardiac disease-e.g.,

TABLE II-RELATION OF BLOOD VISCOSITY TO DEGREE OFVENOUS CONGESTION AS INDICATED BY CYANOSIS IN

PATIENTS UNDER ROUTINE TREATMENT FOR CARDIAC

FAILURE

anaemia, pyrexial diseases, chronic rheumatism-themean value was 4-7 (6-5-3-8). The patients withheart-failure are divided into four groups : (1) thosewith peripheral congestion but no oedema ; (2) thosewith oedema but no peripheral congestion ; (3) thosewith oedema and peripheral congestion; and (4)those without oedema or peripheral congestion butwith dyspnœa and pallor as the main features. Inall these 35 patients the blood viscosity was deter-mined shortly after their admission to hospital.Serial determinations were also carried out on someof these patients during the course of treatment.The viscosities on admission are summarised intablei. These figures show that in patients with heart-failure and no oedema the blood viscosity tends to beraised.

Serial estimations indicate that in this group clinicalimprovement is associated with a fall in viscosity,and clinical deterioration with a rise. This may beillustrated by the findings in 2 patients on routinetreatment for cardiac failure (table n).When there was oedema, but little evidence of

venous congestion or stasis, the viscosity was low. It

appears, therefore, that in cardiac failure the viscosityof the blood is influenced in opposing directions by