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Carcinoma of the stomach
Carcinoma of the Stomach COMPARATIVE
STUDE’ OF ONE HOSPITAL’S
STEPHEN J. HEALEY, M.D. AND THOMASW. BOTSFOKD,M.D.,
From School
the and
Departments the Peter
of Rent
Surgery,
Harvard
Medical
Brigham
Hospital,
Boslon,
Massuchusetts.
1923 Cheever [I] reported the initia1 ten year experience with carcinoma of the stomach at the Peter Bent Brigham Hospital. At that time he said “a record of failure to cure the most common type of maIignant disease is regrettable, but the most discouraging feature is that it is difhcult to see how any very great improvement may be achieved.” The recent experience with gastric cancer has been reviewed at the same hospita1, and it is the purpose of this communication to report this experience and compare it with the materiaI documented by Cheever [I]. An appraisa1 and comparison of the management and results of the treatment of this disease over a span of fifty years at one hospital wiII be presented. It is hoped that an encouraging point of view wiII emerge rather than the prevaIent sense of hopeIessness that is so often associated with carcinoma of the stomach. K
I
EXPERIENCE Adussachu.setts
Brookline,
the 2: I maIe to female incidence frequentIy reported [2,~3]and found in the previous series. A comparison of the ages of incidence shows a definite shift to oIder persons in the present series. (TabIe I.) OnIy I I per cent of the patients were Iess than hfty years old in the present series compared with 33.7 per cent of patients! in the earIy series. The U. S. Bureau of VitaliStatistics [4] in 1939 reported that 63.1 per cent of a11deaths from cancer of the stomach were in men and of these, 92.3 per cent were in persons over fifty years oId. SYMPTOMS The most frequent triad of symptoms was epigastric pain, weight Ioss and anorexia. (Table II.) Pain was the most common symptom, being present in 6g per cent of the present series and 61 per cent of the early series. Pain varied from a duI1 epigastric ache to a vague distress in the same region. Occasionally it had the character of uIcer pain but rarely was it TABLE
MATERIAL
.4GE
The materia1 for this report consists of 247 consecutive cases of carcinoma of the stomach seen at the Peter Bent Brigham Hospital between January 1947 and December 1961. Patients who had been treated surgically eIsewhere prior to
I
INCIDEUCE
-
1913-1922
AgeW
their admission to this hospita1 were excluded from this study. Over g7 per cent of the patients had definitive foIIow-up study. The patients Iost to foIIow-up study were considered dead of their disease when Iast examined. The series of 236 consecutive cases of carcinoma of the stomach seen at this hospital between 1913 and 1922 [I] were used for comparison.
No. of Cases
I ‘er
1!)47-19G1
cent
No.
of
cases
/ per cent
-_2 1-30
2
31-40
20
41-50 TI-Go
58 84
61-70
GO
71-80
I2
81-90
0
Over
SEX AND AGE There were 146 men and IOI women in the present series. This is somewhat Iess than
Total
837
go
0
236
0.8 8.4 24.5 35.5 25.4 5.0 0.0 0.0
0
5 23 53 68 76 21 I
0
0
2
0
9.3 21 .s 27.5 30.8
8.5 0.4
247
American Journal of Surgery, Volume 107, June 1964
HeaIey
and Botsford
TABLE II PRESENTING COMPLAINTS I913-1920
TABLE III DURATION OF SYMPTOMSBEFORE ADMISSION
1947--Ig61
~
CompIaint
Epigastric distress ....... Weight Ioss ............. Anorexia. .............. Nausea and/or vomiting. Fatigue. ............... MeIena. ............... Hematemesis. .......... Dysphagia. ............ Anemia. ...............
No. of Cases
Per cent
I37 4 21
61.2
I53 25 26 48 4 3
I.7 9.4 64.8 II.2 11.0 20.1 I.7 I.3
vo.of 3ases
I72 87 83 68 52 24 ‘4 22 7
Gastric anaIysis. .......... AchIorhydria. .......... Free acid. .............. Stool benzidine ........... Positive. ............... Negative ............... Hematocrit (mg. per cent). Less than 25 ............ 25-36 .................. More than 36 ..........
69.6 35.2 33.6 27.5 21.0 9.7 5.7 9.0 2.8
No. of Cases
Per cent
I72 I30 4I 226
. .
I65 61 243 29 96 118
Ig47-Ig6I
/
Time (mo.) No. of Cases
Per cent
No. of Cases
Per cent
o-3 4-6
83
::
37.0 27.0
7-12 13-24 Over 24
65 33 II
37.7 12.6 29.5
54
22.0
15.2 5.0
22
Per cent
28
I2
9.0 5.0
both series with weight Ioss Iess frequent and vomiting more common in the earIy series. Eight patients had pernicious anemia, and twenty-eight patients had a nonheaIing gastric uIcer or a known gastric uIcer in the past. In ten instances a famiIy history of gastric cancer was present. The usua1 deIay in the diagnosis of carcinoma of the stomach was present as it has been in other series [3,5]. (TabIe III.) There has been no shortening of this deIay in the past fifty years at this hospita1. In both groups 63 per cent of the patients had symptoms for three months or Ionger. These figures reffect the insidious nature of this disease which is present with such vague symptoms that they are unfortunateIy ignored by both physician and patient. PhysicaI frndings in carcinoma of the stomach are not apparent unti1 the tumor has grown big enough to be paIpabIe or has metastasized to a region accessibIe to examination such as the neck, Iiver or pouch of DougIas. In this series an epigastric mass was feIt in over a third of the patients, and the other physica findings were usuaIIy obvious signs of incurabIe carcinoma. in
TABLE Iv LABORATORYTESTS Test
1g13-1922
76 24
... 73 I7
... II 40 49
severe and sharp. Loss of weight was a major compIaint in over 35 per cent of the patients but was found to exist in two thirds. In 165 patients in whom weight Ioss was documented, 90 per cent had Iost more than IO pounds. Loss of appetite was present in a third of the patients and was usuaIIy attributabIe to tasteIessness of food, discomfort after eating or fuIIness after eating very IittIe; these are vague but important symptoms of the disease. Massive gastrointestina1 bIeeding was uncommon, but twenty-four patients had passed gross bIood in their stooIs. Dysphagia was usuaIIy associated with a neopIasm arising in the cardia, and nausea and vomiting were symptoms of an advanced stage of the disease. Fatigue and anemia were associated with one another. A comparison of the symptoms in the two series shows that the same symptoms were common
LABORATORY
FINDINGS
Gastric anaIysis was made in 172 patients and 76 per cent of this group had histamine achIorhydria (TabIe IV); 74 per cent had achIorhydria in Cheever’s [I] series. This is a vaIuabIe test and its use as a screening method in the asymptomatic patient over fifty years of age wouId appear to have merit [6]. Examination of the stoo1 for occuIt bIood was made in 226 patients. A positive test resuIt for occuit bIood was present in 73 per 838
Carcinoma cwt. I-his test should be performed routine11 on a/I patients incIuding office patients. A \pccimcn 01‘ feces is always avaiIabIe on the czaminer’h glo\-e and can be easiIy tested with l,en7idine reagent. Ilematocrit was determined in 243 patients. [Hematocrit of less than 36 per cent was present in 12; of these patients, and in 29 of these hematocrit bvas beIow 25 per cent. These were typica iron deficiency anemias, and onI? rareIy was megaIobIastic anemia found. Exammation of the patient’s bIood type faiIed to show an increased incidence of gastric cancer in patients with type A as reported by others [8,9]. PapanicoIaou smears were taken of gastric in thirty-eight patients, with a secretions positive report in twelve. (TabIe v.) Brandborg [9] has reviewed the fieId of gastric cytologv and reported a 90 per cent positive cytoIogIc examination with Iess than I per cent faIse-positive resuIts. These careful cytoIogic stud& by an enthusiastic group has shown how accurate gastric cytology can be. ROENTGENOGRAPHIC
Positive. Negativr Suspicious. Unsntisfxtorg
TABLE
UPPER
VI
GASTROINTESTINAL
SERIES
Diagnosis
NUIIlber
Carcinoma. Suspicious for carcinoma. Obstruction. Gastritis.. Negative.
~
164 46
cent
68.0 ‘9.3 8.3
20
I, I
Per
2. I I .:
;
EXAMINATION
Upper gastrointestina1 series were performed in 239 patients. These were read as diagnostic for carcinoma in 164 instances. (TabIe VI.) Twenty were interpreted as showing obstruction or partia1 obstruction in the pyIoric area. The report was negative for abnormalities in onIy four patients and read as gastritis in five. These reports were diagnostic or highIy suspicious of carcinoma in 87.9 per cent of the cases. In Cheever’s [r] series 93 per cent of the reports were diagnostic of carcinoma and 3.5 per cent were interpreted as a negative study. Roentgenographic examination remains the best method in the diagnosis of a gastric tumor [Jo]. ENDOSCOPY
Endoscopy was of aid in making the diagnosis in seIected patients and was heIpfu1 in determining the extent of the disease in others. Gastroscopy or esophagoscopy was performed on seventy-five patients. (TabIe VII.) A definite diagnosis of carcinoma was made in forty-eight instances. TweIve endoscopies were unsatisfactory and three were reported as within norma Iimits. In three of the five cases of gastritis reported by upper gastrointestina1 series, a diagnosis of cancer was made by gastroscopy. A diagnosis of cancer was made in one of the
Gastros-
ResuIt
COPY
Carcinoma. ............. Suspicious for carcinoma Unsatisfactory. ..... Negative .......... Total.
.,..I
Esopha-
Total
WSC”PY
Casts
10
38 IO
3 63
48 12
12 ~
.‘;
/ I
12
3
.... 12
75
Iimits four cases reported as within norm4 by roentgenogram. CIarke et a1. [II] reported eighty-one gastroscopic examinations in a series of 250 cases of carcinoma of the stomach, with a positive diagnosis in 65 per cent. Welch and WiIkins [IO] reported eighty-three gastroscopies, with a positive diagnosis in 59 per cent. TREATMENT
Operation was performed on 21 I patients for an operabiIity rate of 85.5 per cent. Curative resection was performed on ninety-nine patients and paIIiative resection on seventyseven. In thirty-six patients no operation was performed because of widespread disease in twenty-one, medica contraindications in nine and refusa1 of surgery in six. (TabIe VIII.)
839
HeaIey
and
Botsford
TABLE VIII ANALYSIS OF OPERABILIT?
TABLE IX OPERATIVE PROCEDURES ON 211 CASES
-
-
I
1g13--1922
hlortality
‘947-1961 Operation
Treatment
No.of Cases
Per cent
No.of( Cases
-___ No operation.. ExpIoration only.. PaIIiative operation. Curative operation. TotaI..
.
-I-
36 35 77
57.6
24
10.2
53 23
22.4
236
..
9.8
99 .___-
100.0
247
14.6 14.2
Laparotomy . .. Bypass. . TotaI gastrectomy. Curative PaIIiative ProximaI gastrectomy . Curative. . PaIIiative . Subtotd gastrectomy Curative. PaIIiative
31.2 40.0 100.0
TABLE x CAUSES OF OPERATIVE MORTALITY
-
! f-
vo.0
Operation
whom
I
gastrectomy.
Proximal
gastrectomy..
Subtotal
gastrectomy.
surgery [2].
TotaI
presentIy
onIy
considered curative
resections
thirty-five ative
a fourth
patients,
mortahty
Cheever’s operation
was
an
18.2
of
curative
on
eighteen
The
106
patients.
and
for
An
anaIysis
This
procedure
[I].
performed used
per
cent
IX.)
A
on nineteen of onIy
were
with
Ieak.
in
per
[12].
patients
are
the
in 840
unresected
In by
hazards
sepsis
operative the
group
death
which extension
the
four
was
Ied
fataIities
gastrectomy
from
anastomotic
emboIism, were
remaining
an with in
this the
anasto-
Iiterature
pneumonia responsibIe patients.
to
into
proxima1
we11 documented
in the
in
Iesion
associated
infarction
cent,
resections
biopsy,
comparison,
operative
mortaIity. of
that
and
on
an operative
causes and
sub-
sixty-one
I I. I per
curative
shows
undergoing
The
and
operative
the
x)
PuImonary deaths
for
hemorrhage
organs.
myocardia1
cent.
of
the
caused
mosis
bypass
patients,
26
by
The
cent
dista1
in
reported
present
Iaparotomy
patients
oper-
identica1
(TabIe
mortaIity was
vita1 in
on
per the
(TabIe
obstruction,
as many
I3
of
is twice
group.
cure
cent
[I ]
Cheever
which
caused
were
6.6 per
in
post-
performed
in forty-five.
were
Two
was
for
both
cure
for
in each was
were
performed
six.
operation
these
in
hope
in
was
of
was
a
on mor-
seven
simiIar
which
paIIiation
undergoing
that
was
with disease
operative
and
with
and These
Twenty-six
occurred
This
-I
33.3 8.5 6.6 11.1
performed
an
paIIiation
gastrectomy
mortaIity
performed
a 20 was
9 4 5
extensive
was
cent.
common
respectiveIy.
patients
was
2 2
impossibIe
gastrectomy
deaths
14.3 22.2 16.7
associated
with
resections
for
most
mortaIities
shows
times
I
4
imminent.
with
patients
and
operative tota
per
ProximaI
tweIve
was
mortahty
mortaIity
groups.
performed.
with
operative
four
biopsy
which
experience
with
and were
with
series
as many
inoperabIe
Laparotomy
initia1
5
33.3 50.3 57.5 42.5
or
patient
patients,
were
20.0 26.3 18.2 19.2
-
gastrectomy
tahty
mortaIity the
:
8.5 66.6
45
present
the
paIIiative;
COh
with
18 I2 6 106 61
the high
on
thirty-three
Duodenal stump leak Myocardial infarction Pulmonary embolus Peritonitis I[nternal hernia and strangulated small bowe1
A comparison
7
9.0 15.6 78.8 21.2
resection
was
resu1t.s show
Carcinomatosis Unrelieved obstruction Bronchopneumonia Hemorrhage Peritonitis Probable pulmonary embolus Acute bronchopneumania and pulmonary embolus Carcinomatosis PuImonary embolus MvocardiaI infarction PGumonia IUnknown cause: died on twentieth postoperative day Sepsis with anastomotic leak jubhepatic abscess and infarction of transverse
..
.
pahiative
obstruction
_-
Tow1
16.6
-
CtUkX
..
35 19 33 26 7
Mortality
zaser
Laparatomy.
No.01 Case:
I-
136
/
Per cent
4
Per cent
-
Bypass.
I
and for
haIf
of Stomach
Carcinoma
1noper:hlr
.................
,
I.apa”‘tomy. ................. Ryp:1ss, .....................
T‘otnl gnstrcctomy ............... Proximd gastrectomy. ......... Suhotnl gastrectomy. ...........
36 35 19 33 18 106
I
3 ; 12 12
Five Year Survivors
SURVIVAL
The median survival in patients not operated on was one month, with thirty-three of being dead within one thirty-six patients year. (Table XI.) A bypass procedure did not prolong life as the median surviva1 was the same as in patients in whom onIy Iaparotomy was performed. SubtotaI gastrectomy was associated with a median survival of one year which was longer than that of the patients surviving total gastrectomy. The reIative five year surviva1 based on a11 curable resections between 1947 and 1957 was 25.6 per cent. (TabIe XII.) There was one five vear survival in twentv-one curative tota iastrectomies and one k&e year surviva1 in ten proxima1 gastrectomies. Nineteen of fiftyone Datients who underwent curative distal subtota1 gastrectomy were Iiving at the end of five years. There were twenty-one patients who survived five years among the 171 patients with carcinoma of the stomach treated between 1947 and 1957 for an absoIute surviva1 of 12.3 per cent. (Table XIII.) This figure shows marked improvement when compared with the earlier series reported from this hospita1 [1,13]. A palpable epigastric mass was present in seventy-one patients and only six of these patients survived five years. The presence of an &kastric mass reduced the five vear surviva1 u by a third and is a poor but not hopeIess prognostic sign 131. Positive Iymph nodes were patients and negative present in fifty-five Iymph nodes in twenty-seven of eighty-two patients who underwent curative resections between 1947 and 1957. (TabIe XIV.) There were nine five year survivors in the positive node group and tweIve five year survivors in the negative node group. The presence of 1
”
841
1913~-IQ22
236
1930-1935 ‘947-1957
107 171
METASTASES
/
;
j 21
TABLE NODE
I
/ Prr cent I
AND I
,
I 2 75 123
XIV CURATIVE I
RESECTION I
,
Curative Resection
,
Positive lymph nodes. _. Negative lymph nodes., l-otnl.......
.__...
positive nodes in a curative resection reduced the chance for five year surviva1 threefold [3,10]. SubtotaI or tota gastrectomy with resection of adjoining organs was performed in thirty-four patients, with an operative mortaIity of 15 per cent and a five year surviva1 of 8.8 per cent. There were no five year survivors among patients requiring partial hepatectomy. Others have reported a similar increase in operative mortality and decrease in five year surviva1 when resection of continuous organs was necessary [3,ro]. FIVE
YEAR
SURVIVORS
A carefu1 anaIysis was made of the twentyone patients who survived five years. These patients were compared with the tota series of patients [~a]. No significant differences in age, sex, Iaboratory findings or symptoms were apparent. There were eIeven maIe and ten femaIe patients in the five year surviva1 group.
HeaIey
and Botsford
It is of interest that nine of the twenty-one five year survivors had symptoms of Iess than three months’ d.uration. Nineteen Iong-term survivors underwent subtota1 gastric resection for poIypoid or uIcerative neopIasms of the dista1 one third of the stomach. One tota gastrectomy and one proxima1 gastrectomy were performed for lesions Iocated in the fundus. None of the tumors in this group were diffuseIy infiItrating, and onIy one penetrated the serosa. Nine of these patients had Iymph node metastases. The only significant factor in the five year survivors when compared with the entire series was a shorter duration of symptoms. No other cIinica1 finding could be associated with these five year “cures.”
and in another report [rj] in 1934 this figure was 7.5 per cent. It is presentIy 12.3 per cent. In the years Igr3 to 1923, the operative mortaIity was 13 per cent in curative resections but it increased to 23 per cent between 1931 and 1941 [r?]. The present operative mortaIity for subtota1 gastric resections is 6.6 per cent. These figures are far from idea1 but they do indicate that progress has been made. We beIieve the operation of choice for carcinoma of the stomach is dista1 subtota1 gastrectomy with wide excision of both omenta, duodena1 cuff and high gastric transection. This operation gives the highest five year surviva1 with the Iowest mortality and morbidity [3,10,15]. TotaI gastrectomy shouId be reserved for those patients in whom the Iesion cannot be resected by a Iesser procedure and cure is a possibiIity [I I, 15,16]. TotaI gastrectomy has no pIace as a paIIiative procedure because of its high mortaIity and morbidity [17]. ProximaI gastrectomy is the operation of choice for Iesions of the cardia. This operation has a IO per cent five year surviva1 and a 22 per cent operative mortaIity. The hazard of anastomotic Ieaks with this operation is we11 known [IZ] and was responsibIe for a11 the postoperative deaths. The Iow surviva1 for Iesions of the cardia is thought to be the resuIt of earIy metastases to mediastina1 nodes and IocaI infiItration of the esophagus. Operation is indicated for paIIiation as x-ray therapy, bouginage and bypass are ineffective in treating patients with adenocarcinoma of the proxima1 stomach [IS]. DistaI subtota1 resection is the operation of choice for paIIiation for the incurabIe patient. Mortality is Iow and the result in terms of proIonged comfort is good. A bypass procedure shouId be avoided if possible because of its high mortaIity and its faiIure to reIieve symptoms or proIong Iife [r6].
COMMENTS
The singIe most formidabIe obstacIe to success in the present treatment of carcinoma of the stomach is delay in diagnosis. In this hospita1 no appreciabIe improvement in this factor is discernibIe over a period of aImost haIf a century. Over 60 per cent of the present series of patients entered the hospita1 because of symptoms of over three months’ duration and this was true over forty years ago at this hospita1. One may bIame the insidious nature of the disease for this discouraging Iack of progress. However, the physician and patient must share responsibiIity for the deIay in diagnosis: the physician because of errors of omission and the patient for negIect of symptoms. The patient with vague epigastric compIaints must be examined to find the cause. The investigation should incIude determination of hematocrit, tests for occuIt bIood in the stoo1, gastric anaIysis and barium roentgenographic studies of the upper gastrointestinal tract. This can be restated to say that it is mandatory for every physician to have a high index of suspicion of the possibiIity of carcinoma of the stomach in each patient with symptoms referrabIe to the upper gastrointestinal tract no matter how vague they may be, A more encouraging note is the fact that progress has been made in the surgical treatment of the disease. Twice as many patients are being operated upon and four times as many resections for cure are being made. At the same time there is presentIy a Iower operative mortaIity. In 1923 a report [I] from this hospita1 Iisted an absoIute five year surviva1 in carcinoma of the stomach of 1.2 per cent
CONCLUSION
A study of a11 cases of carcinoma of the stomach at the Peter Bent Brigham HospitaI in 1913 through 1923 and 1947 through 1961 has shown a tenfoId increase in five year survivaI. There has been no shortening of the deIay in diagnosis. We beIieve that dista1 subtota gastrectomy is the operation of choice for carcinoma of the stomach. The five year survivors showed no significant clinica difference 842
Grcinoma i’rc~n~the entire group> except a shorter
of Stomach
dwxtion
KEFERENCES I. (:lrb.b.\ b.H, I>. The
non,:,
of
the
operative curability stonxrch. Ann. Surg.,
of carci-
$4: 332,
‘923. 2. 11cN~m,
3.
4.
5. 6.
7.
8.
g.
G.. LAWhUGE, b’., JK., ASHLEY, 31. I’. ;rnd PA(:K, G. T. End rcsufts in the trea?mcnt of gastric cancer. Surgery, 43: 879, 1958. \IARSIIAI.~., S. F. Treatment of cancer of the stomach: end results. Gastroenterolog~, 34: 34, ‘958. Vital Statistics of the United States, vol. 2, 1959. U. S. Department of Health, Education, and Welfare. Sfrk~ov, D. B., HOROWITZ, S. and KELLY, W. D. Cancer of the stomach. Surgery, 39: 204, 1956. I~ITC~ICOCK, C. R., SCILLIVAK,W. A. and WA?,cEuSTEEN, 0. H. The vaIue of achlorhydria as a screening test for gastric cancer: a ten year report. Gastroenterology, 29: 621, 1955. AIRD, I., BENTALL, H. II., FRASER-ROBERTS, J. A. A reIationship between cancer of stomach and the ABO blood groups. Brit. M. J., I : 799, 1953. B~,CKWALTER, J. A., WOHLWEND, C. B., COLTER, D. L., TIDKICK, R. T. and KNOWLES, L. A. The association of the ABO blood groups to gastric carcinoma. Surg. G?/nec. e? Obst., 104: 176, 1957. BRAXDBORG, L. L. ExfoIiative CytoIogy in Surgery of the Stomach and Duodenum, p. 133. Edited
843
14. BROWN, C. tl., ~IEIILO, hl. and fIALru,.I. B. CIinicaI stucIy of five year survivors :Il’tr,r surgery for gastric carcinoma. Castroenterolo~~,, 40: 188, 1961.
IS. Rusq
B. F., JR., BROWK, hl. M:. and KA\YTCII, TotaI gastrectomy: an evaIu;ltion of its use in the treatment of gastric cancer. (,&cer. 13: 643, 1960. 16. LAWRENCE. , \V.. JR. and I\IcNEER. G. An anal&s of the roIe of radica1 surgery for gastric cancer. Surp. Gynec. CYObst., I I I : 691, 1960. 17. LAWRENCE, b’., JI<. and MCNEER, G. The cffcctivrncss of surgery for palliation of incurable gastric cancer. Cancer, II: 28, 1958. 18. EI.LIS, F. H., JACKSON, R. C., KRL.E(;EK, J. T., .JR., MOEIGCH, J. J., CLA~XETT, 0. T. and G*GE, R. I’. Carcinoma of the esophagus and cardia: results of treatment Ig46Pr9s6. Nelc Englund J. Med., 260: 351, 1959. hf.
hf.
STUDE’ OF ONE HOSPITAL’S
STEPHEN J. HEALEY, M.D. AND THOMASW. BOTSFOKD,M.D.,
From School
the and
Departments the Peter
of Rent
Surgery,
Harvard
Medical
Brigham
Hospital,
Boslon,
Massuchusetts.
1923 Cheever [I] reported the initia1 ten year experience with carcinoma of the stomach at the Peter Bent Brigham Hospital. At that time he said “a record of failure to cure the most common type of maIignant disease is regrettable, but the most discouraging feature is that it is difhcult to see how any very great improvement may be achieved.” The recent experience with gastric cancer has been reviewed at the same hospita1, and it is the purpose of this communication to report this experience and compare it with the materiaI documented by Cheever [I]. An appraisa1 and comparison of the management and results of the treatment of this disease over a span of fifty years at one hospital wiII be presented. It is hoped that an encouraging point of view wiII emerge rather than the prevaIent sense of hopeIessness that is so often associated with carcinoma of the stomach. K
I
EXPERIENCE Adussachu.setts
Brookline,
the 2: I maIe to female incidence frequentIy reported [2,~3]and found in the previous series. A comparison of the ages of incidence shows a definite shift to oIder persons in the present series. (TabIe I.) OnIy I I per cent of the patients were Iess than hfty years old in the present series compared with 33.7 per cent of patients! in the earIy series. The U. S. Bureau of VitaliStatistics [4] in 1939 reported that 63.1 per cent of a11deaths from cancer of the stomach were in men and of these, 92.3 per cent were in persons over fifty years oId. SYMPTOMS The most frequent triad of symptoms was epigastric pain, weight Ioss and anorexia. (Table II.) Pain was the most common symptom, being present in 6g per cent of the present series and 61 per cent of the early series. Pain varied from a duI1 epigastric ache to a vague distress in the same region. Occasionally it had the character of uIcer pain but rarely was it TABLE
MATERIAL
.4GE
The materia1 for this report consists of 247 consecutive cases of carcinoma of the stomach seen at the Peter Bent Brigham Hospital between January 1947 and December 1961. Patients who had been treated surgically eIsewhere prior to
I
INCIDEUCE
-
1913-1922
AgeW
their admission to this hospita1 were excluded from this study. Over g7 per cent of the patients had definitive foIIow-up study. The patients Iost to foIIow-up study were considered dead of their disease when Iast examined. The series of 236 consecutive cases of carcinoma of the stomach seen at this hospital between 1913 and 1922 [I] were used for comparison.
No. of Cases
I ‘er
1!)47-19G1
cent
No.
of
cases
/ per cent
-_2 1-30
2
31-40
20
41-50 TI-Go
58 84
61-70
GO
71-80
I2
81-90
0
Over
SEX AND AGE There were 146 men and IOI women in the present series. This is somewhat Iess than
Total
837
go
0
236
0.8 8.4 24.5 35.5 25.4 5.0 0.0 0.0
0
5 23 53 68 76 21 I
0
0
2
0
9.3 21 .s 27.5 30.8
8.5 0.4
247
American Journal of Surgery, Volume 107, June 1964
HeaIey
and Botsford
TABLE II PRESENTING COMPLAINTS I913-1920
TABLE III DURATION OF SYMPTOMSBEFORE ADMISSION
1947--Ig61
~
CompIaint
Epigastric distress ....... Weight Ioss ............. Anorexia. .............. Nausea and/or vomiting. Fatigue. ............... MeIena. ............... Hematemesis. .......... Dysphagia. ............ Anemia. ...............
No. of Cases
Per cent
I37 4 21
61.2
I53 25 26 48 4 3
I.7 9.4 64.8 II.2 11.0 20.1 I.7 I.3
vo.of 3ases
I72 87 83 68 52 24 ‘4 22 7
Gastric anaIysis. .......... AchIorhydria. .......... Free acid. .............. Stool benzidine ........... Positive. ............... Negative ............... Hematocrit (mg. per cent). Less than 25 ............ 25-36 .................. More than 36 ..........
69.6 35.2 33.6 27.5 21.0 9.7 5.7 9.0 2.8
No. of Cases
Per cent
I72 I30 4I 226
. .
I65 61 243 29 96 118
Ig47-Ig6I
/
Time (mo.) No. of Cases
Per cent
No. of Cases
Per cent
o-3 4-6
83
::
37.0 27.0
7-12 13-24 Over 24
65 33 II
37.7 12.6 29.5
54
22.0
15.2 5.0
22
Per cent
28
I2
9.0 5.0
both series with weight Ioss Iess frequent and vomiting more common in the earIy series. Eight patients had pernicious anemia, and twenty-eight patients had a nonheaIing gastric uIcer or a known gastric uIcer in the past. In ten instances a famiIy history of gastric cancer was present. The usua1 deIay in the diagnosis of carcinoma of the stomach was present as it has been in other series [3,5]. (TabIe III.) There has been no shortening of this deIay in the past fifty years at this hospita1. In both groups 63 per cent of the patients had symptoms for three months or Ionger. These figures reffect the insidious nature of this disease which is present with such vague symptoms that they are unfortunateIy ignored by both physician and patient. PhysicaI frndings in carcinoma of the stomach are not apparent unti1 the tumor has grown big enough to be paIpabIe or has metastasized to a region accessibIe to examination such as the neck, Iiver or pouch of DougIas. In this series an epigastric mass was feIt in over a third of the patients, and the other physica findings were usuaIIy obvious signs of incurabIe carcinoma. in
TABLE Iv LABORATORYTESTS Test
1g13-1922
76 24
... 73 I7
... II 40 49
severe and sharp. Loss of weight was a major compIaint in over 35 per cent of the patients but was found to exist in two thirds. In 165 patients in whom weight Ioss was documented, 90 per cent had Iost more than IO pounds. Loss of appetite was present in a third of the patients and was usuaIIy attributabIe to tasteIessness of food, discomfort after eating or fuIIness after eating very IittIe; these are vague but important symptoms of the disease. Massive gastrointestina1 bIeeding was uncommon, but twenty-four patients had passed gross bIood in their stooIs. Dysphagia was usuaIIy associated with a neopIasm arising in the cardia, and nausea and vomiting were symptoms of an advanced stage of the disease. Fatigue and anemia were associated with one another. A comparison of the symptoms in the two series shows that the same symptoms were common
LABORATORY
FINDINGS
Gastric anaIysis was made in 172 patients and 76 per cent of this group had histamine achIorhydria (TabIe IV); 74 per cent had achIorhydria in Cheever’s [I] series. This is a vaIuabIe test and its use as a screening method in the asymptomatic patient over fifty years of age wouId appear to have merit [6]. Examination of the stoo1 for occuIt bIood was made in 226 patients. A positive test resuIt for occuit bIood was present in 73 per 838
Carcinoma cwt. I-his test should be performed routine11 on a/I patients incIuding office patients. A \pccimcn 01‘ feces is always avaiIabIe on the czaminer’h glo\-e and can be easiIy tested with l,en7idine reagent. Ilematocrit was determined in 243 patients. [Hematocrit of less than 36 per cent was present in 12; of these patients, and in 29 of these hematocrit bvas beIow 25 per cent. These were typica iron deficiency anemias, and onI? rareIy was megaIobIastic anemia found. Exammation of the patient’s bIood type faiIed to show an increased incidence of gastric cancer in patients with type A as reported by others [8,9]. PapanicoIaou smears were taken of gastric in thirty-eight patients, with a secretions positive report in twelve. (TabIe v.) Brandborg [9] has reviewed the fieId of gastric cytologv and reported a 90 per cent positive cytoIogIc examination with Iess than I per cent faIse-positive resuIts. These careful cytoIogic stud& by an enthusiastic group has shown how accurate gastric cytology can be. ROENTGENOGRAPHIC
Positive. Negativr Suspicious. Unsntisfxtorg
TABLE
UPPER
VI
GASTROINTESTINAL
SERIES
Diagnosis
NUIIlber
Carcinoma. Suspicious for carcinoma. Obstruction. Gastritis.. Negative.
~
164 46
cent
68.0 ‘9.3 8.3
20
I, I
Per
2. I I .:
;
EXAMINATION
Upper gastrointestina1 series were performed in 239 patients. These were read as diagnostic for carcinoma in 164 instances. (TabIe VI.) Twenty were interpreted as showing obstruction or partia1 obstruction in the pyIoric area. The report was negative for abnormalities in onIy four patients and read as gastritis in five. These reports were diagnostic or highIy suspicious of carcinoma in 87.9 per cent of the cases. In Cheever’s [r] series 93 per cent of the reports were diagnostic of carcinoma and 3.5 per cent were interpreted as a negative study. Roentgenographic examination remains the best method in the diagnosis of a gastric tumor [Jo]. ENDOSCOPY
Endoscopy was of aid in making the diagnosis in seIected patients and was heIpfu1 in determining the extent of the disease in others. Gastroscopy or esophagoscopy was performed on seventy-five patients. (TabIe VII.) A definite diagnosis of carcinoma was made in forty-eight instances. TweIve endoscopies were unsatisfactory and three were reported as within norma Iimits. In three of the five cases of gastritis reported by upper gastrointestina1 series, a diagnosis of cancer was made by gastroscopy. A diagnosis of cancer was made in one of the
Gastros-
ResuIt
COPY
Carcinoma. ............. Suspicious for carcinoma Unsatisfactory. ..... Negative .......... Total.
.,..I
Esopha-
Total
WSC”PY
Casts
10
38 IO
3 63
48 12
12 ~
.‘;
/ I
12
3
.... 12
75
Iimits four cases reported as within norm4 by roentgenogram. CIarke et a1. [II] reported eighty-one gastroscopic examinations in a series of 250 cases of carcinoma of the stomach, with a positive diagnosis in 65 per cent. Welch and WiIkins [IO] reported eighty-three gastroscopies, with a positive diagnosis in 59 per cent. TREATMENT
Operation was performed on 21 I patients for an operabiIity rate of 85.5 per cent. Curative resection was performed on ninety-nine patients and paIIiative resection on seventyseven. In thirty-six patients no operation was performed because of widespread disease in twenty-one, medica contraindications in nine and refusa1 of surgery in six. (TabIe VIII.)
839
HeaIey
and
Botsford
TABLE VIII ANALYSIS OF OPERABILIT?
TABLE IX OPERATIVE PROCEDURES ON 211 CASES
-
-
I
1g13--1922
hlortality
‘947-1961 Operation
Treatment
No.of Cases
Per cent
No.of( Cases
-___ No operation.. ExpIoration only.. PaIIiative operation. Curative operation. TotaI..
.
-I-
36 35 77
57.6
24
10.2
53 23
22.4
236
..
9.8
99 .___-
100.0
247
14.6 14.2
Laparotomy . .. Bypass. . TotaI gastrectomy. Curative PaIIiative ProximaI gastrectomy . Curative. . PaIIiative . Subtotd gastrectomy Curative. PaIIiative
31.2 40.0 100.0
TABLE x CAUSES OF OPERATIVE MORTALITY
-
! f-
vo.0
Operation
whom
I
gastrectomy.
Proximal
gastrectomy..
Subtotal
gastrectomy.
surgery [2].
TotaI
presentIy
onIy
considered curative
resections
thirty-five ative
a fourth
patients,
mortahty
Cheever’s operation
was
an
18.2
of
curative
on
eighteen
The
106
patients.
and
for
An
anaIysis
This
procedure
[I].
performed used
per
cent
IX.)
A
on nineteen of onIy
were
with
Ieak.
in
per
[12].
patients
are
the
in 840
unresected
In by
hazards
sepsis
operative the
group
death
which extension
the
four
was
Ied
fataIities
gastrectomy
from
anastomotic
emboIism, were
remaining
an with in
this the
anasto-
Iiterature
pneumonia responsibIe patients.
to
into
proxima1
we11 documented
in the
in
Iesion
associated
infarction
cent,
resections
biopsy,
comparison,
operative
mortaIity. of
that
and
on
an operative
causes and
sub-
sixty-one
I I. I per
curative
shows
undergoing
The
and
operative
the
x)
PuImonary deaths
for
hemorrhage
organs.
myocardia1
cent.
of
the
caused
mosis
bypass
patients,
26
by
The
cent
dista1
in
reported
present
Iaparotomy
patients
oper-
identica1
(TabIe
mortaIity was
vita1 in
on
per the
(TabIe
obstruction,
as many
I3
of
is twice
group.
cure
cent
[I ]
Cheever
which
caused
were
6.6 per
in
post-
performed
in forty-five.
were
Two
was
for
both
cure
for
in each was
were
performed
six.
operation
these
in
hope
in
was
of
was
a
on mor-
seven
simiIar
which
paIIiation
undergoing
that
was
with disease
operative
and
with
and These
Twenty-six
occurred
This
-I
33.3 8.5 6.6 11.1
performed
an
paIIiation
gastrectomy
mortaIity
performed
a 20 was
9 4 5
extensive
was
cent.
common
respectiveIy.
patients
was
2 2
impossibIe
gastrectomy
deaths
14.3 22.2 16.7
associated
with
resections
for
most
mortaIities
shows
times
I
4
imminent.
with
patients
and
operative tota
per
ProximaI
tweIve
was
mortahty
mortaIity
groups.
performed.
with
operative
four
biopsy
which
experience
with
and were
with
series
as many
inoperabIe
Laparotomy
initia1
5
33.3 50.3 57.5 42.5
or
patient
patients,
were
20.0 26.3 18.2 19.2
-
gastrectomy
tahty
mortaIity the
:
8.5 66.6
45
present
the
paIIiative;
COh
with
18 I2 6 106 61
the high
on
thirty-three
Duodenal stump leak Myocardial infarction Pulmonary embolus Peritonitis I[nternal hernia and strangulated small bowe1
A comparison
7
9.0 15.6 78.8 21.2
resection
was
resu1t.s show
Carcinomatosis Unrelieved obstruction Bronchopneumonia Hemorrhage Peritonitis Probable pulmonary embolus Acute bronchopneumania and pulmonary embolus Carcinomatosis PuImonary embolus MvocardiaI infarction PGumonia IUnknown cause: died on twentieth postoperative day Sepsis with anastomotic leak jubhepatic abscess and infarction of transverse
..
.
pahiative
obstruction
_-
Tow1
16.6
-
CtUkX
..
35 19 33 26 7
Mortality
zaser
Laparatomy.
No.01 Case:
I-
136
/
Per cent
4
Per cent
-
Bypass.
I
and for
haIf
of Stomach
Carcinoma
1noper:hlr
.................
,
I.apa”‘tomy. ................. Ryp:1ss, .....................
T‘otnl gnstrcctomy ............... Proximd gastrectomy. ......... Suhotnl gastrectomy. ...........
36 35 19 33 18 106
I
3 ; 12 12
Five Year Survivors
SURVIVAL
The median survival in patients not operated on was one month, with thirty-three of being dead within one thirty-six patients year. (Table XI.) A bypass procedure did not prolong life as the median surviva1 was the same as in patients in whom onIy Iaparotomy was performed. SubtotaI gastrectomy was associated with a median survival of one year which was longer than that of the patients surviving total gastrectomy. The reIative five year surviva1 based on a11 curable resections between 1947 and 1957 was 25.6 per cent. (TabIe XII.) There was one five vear survival in twentv-one curative tota iastrectomies and one k&e year surviva1 in ten proxima1 gastrectomies. Nineteen of fiftyone Datients who underwent curative distal subtota1 gastrectomy were Iiving at the end of five years. There were twenty-one patients who survived five years among the 171 patients with carcinoma of the stomach treated between 1947 and 1957 for an absoIute surviva1 of 12.3 per cent. (Table XIII.) This figure shows marked improvement when compared with the earlier series reported from this hospita1 [1,13]. A palpable epigastric mass was present in seventy-one patients and only six of these patients survived five years. The presence of an &kastric mass reduced the five vear surviva1 u by a third and is a poor but not hopeIess prognostic sign 131. Positive Iymph nodes were patients and negative present in fifty-five Iymph nodes in twenty-seven of eighty-two patients who underwent curative resections between 1947 and 1957. (TabIe XIV.) There were nine five year survivors in the positive node group and tweIve five year survivors in the negative node group. The presence of 1
”
841
1913~-IQ22
236
1930-1935 ‘947-1957
107 171
METASTASES
/
;
j 21
TABLE NODE
I
/ Prr cent I
AND I
,
I 2 75 123
XIV CURATIVE I
RESECTION I
,
Curative Resection
,
Positive lymph nodes. _. Negative lymph nodes., l-otnl.......
.__...
positive nodes in a curative resection reduced the chance for five year surviva1 threefold [3,10]. SubtotaI or tota gastrectomy with resection of adjoining organs was performed in thirty-four patients, with an operative mortaIity of 15 per cent and a five year surviva1 of 8.8 per cent. There were no five year survivors among patients requiring partial hepatectomy. Others have reported a similar increase in operative mortality and decrease in five year surviva1 when resection of continuous organs was necessary [3,ro]. FIVE
YEAR
SURVIVORS
A carefu1 anaIysis was made of the twentyone patients who survived five years. These patients were compared with the tota series of patients [~a]. No significant differences in age, sex, Iaboratory findings or symptoms were apparent. There were eIeven maIe and ten femaIe patients in the five year surviva1 group.
HeaIey
and Botsford
It is of interest that nine of the twenty-one five year survivors had symptoms of Iess than three months’ d.uration. Nineteen Iong-term survivors underwent subtota1 gastric resection for poIypoid or uIcerative neopIasms of the dista1 one third of the stomach. One tota gastrectomy and one proxima1 gastrectomy were performed for lesions Iocated in the fundus. None of the tumors in this group were diffuseIy infiItrating, and onIy one penetrated the serosa. Nine of these patients had Iymph node metastases. The only significant factor in the five year survivors when compared with the entire series was a shorter duration of symptoms. No other cIinica1 finding could be associated with these five year “cures.”
and in another report [rj] in 1934 this figure was 7.5 per cent. It is presentIy 12.3 per cent. In the years Igr3 to 1923, the operative mortaIity was 13 per cent in curative resections but it increased to 23 per cent between 1931 and 1941 [r?]. The present operative mortaIity for subtota1 gastric resections is 6.6 per cent. These figures are far from idea1 but they do indicate that progress has been made. We beIieve the operation of choice for carcinoma of the stomach is dista1 subtota1 gastrectomy with wide excision of both omenta, duodena1 cuff and high gastric transection. This operation gives the highest five year surviva1 with the Iowest mortality and morbidity [3,10,15]. TotaI gastrectomy shouId be reserved for those patients in whom the Iesion cannot be resected by a Iesser procedure and cure is a possibiIity [I I, 15,16]. TotaI gastrectomy has no pIace as a paIIiative procedure because of its high mortaIity and morbidity [17]. ProximaI gastrectomy is the operation of choice for Iesions of the cardia. This operation has a IO per cent five year surviva1 and a 22 per cent operative mortaIity. The hazard of anastomotic Ieaks with this operation is we11 known [IZ] and was responsibIe for a11 the postoperative deaths. The Iow surviva1 for Iesions of the cardia is thought to be the resuIt of earIy metastases to mediastina1 nodes and IocaI infiItration of the esophagus. Operation is indicated for paIIiation as x-ray therapy, bouginage and bypass are ineffective in treating patients with adenocarcinoma of the proxima1 stomach [IS]. DistaI subtota1 resection is the operation of choice for paIIiation for the incurabIe patient. Mortality is Iow and the result in terms of proIonged comfort is good. A bypass procedure shouId be avoided if possible because of its high mortaIity and its faiIure to reIieve symptoms or proIong Iife [r6].
COMMENTS
The singIe most formidabIe obstacIe to success in the present treatment of carcinoma of the stomach is delay in diagnosis. In this hospita1 no appreciabIe improvement in this factor is discernibIe over a period of aImost haIf a century. Over 60 per cent of the present series of patients entered the hospita1 because of symptoms of over three months’ duration and this was true over forty years ago at this hospita1. One may bIame the insidious nature of the disease for this discouraging Iack of progress. However, the physician and patient must share responsibiIity for the deIay in diagnosis: the physician because of errors of omission and the patient for negIect of symptoms. The patient with vague epigastric compIaints must be examined to find the cause. The investigation should incIude determination of hematocrit, tests for occuIt bIood in the stoo1, gastric anaIysis and barium roentgenographic studies of the upper gastrointestinal tract. This can be restated to say that it is mandatory for every physician to have a high index of suspicion of the possibiIity of carcinoma of the stomach in each patient with symptoms referrabIe to the upper gastrointestinal tract no matter how vague they may be, A more encouraging note is the fact that progress has been made in the surgical treatment of the disease. Twice as many patients are being operated upon and four times as many resections for cure are being made. At the same time there is presentIy a Iower operative mortaIity. In 1923 a report [I] from this hospita1 Iisted an absoIute five year surviva1 in carcinoma of the stomach of 1.2 per cent
CONCLUSION
A study of a11 cases of carcinoma of the stomach at the Peter Bent Brigham HospitaI in 1913 through 1923 and 1947 through 1961 has shown a tenfoId increase in five year survivaI. There has been no shortening of the deIay in diagnosis. We beIieve that dista1 subtota gastrectomy is the operation of choice for carcinoma of the stomach. The five year survivors showed no significant clinica difference 842
Grcinoma i’rc~n~the entire group> except a shorter
of Stomach
dwxtion
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non,:,
of
the
operative curability stonxrch. Ann. Surg.,
of carci-
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3.
4.
5. 6.
7.
8.
g.
G.. LAWhUGE, b’., JK., ASHLEY, 31. I’. ;rnd PA(:K, G. T. End rcsufts in the trea?mcnt of gastric cancer. Surgery, 43: 879, 1958. \IARSIIAI.~., S. F. Treatment of cancer of the stomach: end results. Gastroenterolog~, 34: 34, ‘958. Vital Statistics of the United States, vol. 2, 1959. U. S. Department of Health, Education, and Welfare. Sfrk~ov, D. B., HOROWITZ, S. and KELLY, W. D. Cancer of the stomach. Surgery, 39: 204, 1956. I~ITC~ICOCK, C. R., SCILLIVAK,W. A. and WA?,cEuSTEEN, 0. H. The vaIue of achlorhydria as a screening test for gastric cancer: a ten year report. Gastroenterology, 29: 621, 1955. AIRD, I., BENTALL, H. II., FRASER-ROBERTS, J. A. A reIationship between cancer of stomach and the ABO blood groups. Brit. M. J., I : 799, 1953. B~,CKWALTER, J. A., WOHLWEND, C. B., COLTER, D. L., TIDKICK, R. T. and KNOWLES, L. A. The association of the ABO blood groups to gastric carcinoma. Surg. G?/nec. e? Obst., 104: 176, 1957. BRAXDBORG, L. L. ExfoIiative CytoIogy in Surgery of the Stomach and Duodenum, p. 133. Edited
843
14. BROWN, C. tl., ~IEIILO, hl. and fIALru
IS. Rusq
B. F., JR., BROWK, hl. M:. and KA\YTCII, TotaI gastrectomy: an evaIu;ltion of its use in the treatment of gastric cancer. (,&cer. 13: 643, 1960. 16. LAWRENCE. , \V.. JR. and I\IcNEER. G. An anal&s of the roIe of radica1 surgery for gastric cancer. Surp. Gynec. CYObst., I I I : 691, 1960. 17. LAWRENCE, b’., JI<. and MCNEER, G. The cffcctivrncss of surgery for palliation of incurable gastric cancer. Cancer, II: 28, 1958. 18. EI.LIS, F. H., JACKSON, R. C., KRL.E(;EK, J. T., .JR., MOEIGCH, J. J., CLA~XETT, 0. T. and G*GE, R. I’. Carcinoma of the esophagus and cardia: results of treatment Ig46Pr9s6. Nelc Englund J. Med., 260: 351, 1959. hf.
hf.