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Primary malignant tumors of the small intestine
Primary
KEDENTCIR
T two
Malignant Tumors Small Intestine
.1.G. PAGTALLxAK,
nr.D., CHARLES \\-.Y~1.41.0, M.D. AND Rochester, 2\linnesota
STOMACH and
AIATEKIAL AND
METHODS
Kevielv was made of the records oft he 370 hIayo Clinic patients having malignant tumor of the smaI1 intc.stinc in the twenty-five year period, 1037 through 1961. The resected specimens wcrc siudicd and forty-three wcrc excluded from this series: tncnty-eight secondary, elel en rccurrcnt and four incidental tumors. The 327 cases remaining after exclusion formed the basis of this invcstigation. Clinical, laboratory, surgical and pathologic aspects of these cast’s were reviewed and inquir>was msdt as to survival after operation. FINDINGS
and Distribution: From operations for primary mabgnant lesions of the smaI1 bowel at the Mayo Chic averaged about eIeven per year; but from 1955 through 1961, the average was eighteen. Thus about 25 per cent of the tumors studied were excised in the fI\-e years 1953 through 1939, and about I_C per cent in the last t\yo scars covered. The distribution of patients by age and sey followed the pattern generally associated with General.
1937
through
~IALCOLM
B. DOCKERT\-,
M.D.,
malignant growths in the stomach, colon and other organs. An abrupt increase in number iiJlt,Lved the fourth decade of life, and the greatest frequency (3-j per cent) was in the sisth decade. The patients ranged from twenty months to tight!--three years in age, with a mean of Iilt~.-& years. There were 207 males, predominating c,v& females by a ratio of I.;: I. Diagnostic Data: Thirty-four per cent of the patients had develupecl symptoms and signs less than six months before operation, 31 per cent \I-ithin six to twelve months of it, and 3 per cent mot-c than five \-cars preoperativelq. Abdominal pain (213 cases) and Ioss of weight (I 39 cases) were the most common complaint>. The pain was dcacribed uauaIly as intermittent or crampy. Vomiting (103 cases) often occurred earIv in the course. Bowel dysfunction (ninety-k cascb) occurred as diarrhea or constipation; gastrointestinal bkcding (eight)--live casesj was mosti>- in the form ()I’ mcIena. Vague and general complaints wcrc present in a significant number cjf casts: flatulent tlyspt’psia in sist\--one, ilnoresia in forty-eight, anemia in thirty-five, and jaundice in eight. An abdominal mass was palpated in ninety -severs patients; varying degrees of tenderness xere found in fort\--nine, n.nd abdominal cli5tention in twenty-nine. In many case>, complaints due to small bowe1 mnlignanc> sinlulated those of peptic, choIecystic or pancreatic disease, suggesting diflieuity in the upper part of the abdomen; in uthcrs the symptoms mimicked cnterocolitis or diverticulitis, suggesting a more dista1 pathologic process. Presented often was the problem of indeterminate tumor or indeterminate gastrointestinal bleeding. R:tdiologicaIl~, the lesion was interpreted as obstructive in most cases and ulcerative, poly-
the large intestine are \‘ery common sites for development ol’ primary malignant disease. By contrast, malignant neopIasms of the small primary intestine are so rare that their diagnosis often is made by exclusion. This does not promote early dixgnosis with increased opportunity for cure. The foIIowing report is designed to emphasize the clinica and pathologic features, as well x the prognostic implications, in a sizable series of patients with primary maIignancy of the small intestine. HE
of the
Incidence
195-1,
I3
Amel-ica?z JournalofSurgery, Volume
108, Jul\
1064
Pagtahnan, PRIMARY
MALIGNANT
TUMORS
OF
Mayo
and Dockerty
TABLE
I
SMALL
INTESTINE:
PATHOLOGIC I
___ -.__ Duodenum..... Jeiunum..
i
_____
__I_.-._
65
.
-+:+-
22
Total..
LOCATION
AND
)
.t.
58
32
I
6
4
129
68
1
61
16
2
7. /
47
(
poid or intussusceptive in others. The radioIogist diagnosed a carcinomatous lesion in thirty-nine cases, obstructive tumor in thirtyseven and dilated Ioops of bowe1 in eIeven. The smaI1 bowe1 series (barium swaIIow) indicated no abnormaIity in twenty-two instances. Preoperative laboratory studies reveaIed that seventy patients (21 per cent) had a hemogIobin concentration of Iess than IO gm. per IOO ml. of bIood and erythrocyte sedimentation was:greater than Ig mm. in one hour (Westergren) in 66 per cent of the cases in which it was determined. The three most common associated conditions were diverticuIa in thirty-six cases, peptic uIcer in twenty-eight and gaIIbIadder disease in twenty-five. Pathology: The iIeum was the site of 41 per cent of the neopIasms, the jejunum of 36 per cent and the duodenum of 18 per cent. The site of 5 per cent was not specified. (TabIe I.) TABLE PRIMARY MALIGNANT RECORDED
Size (cm.)
BY
41
_(
_.__ Ilrum. ~~ Unspecified.,
-_-
I
DISTKIBUTION
TYPE
Ade?o‘,“di
---
Carci_
noid
-I-
Of the 244 Iesions whose size was recorded, 50 per cent had diameters in the range of I to 5 cm. and 48 per cent were larger. OnIy five tumors were smaIIer than I cm. (TabIe II.) The growths were described as uIcerative in 105 cases, annuIar in sixty-eight and poIypoid in twenty-two. They were perforating in twenty-two cases and intussuscepting in ten. Cavitation and interna fistula were observed in eight cases (Ieiomyosarcoma). Two specimens (maIignant Iymphoma) were aneurysmal in appearance. Among the 249 Iesions whose grade of maIignancy (Broders) was recorded, 38 per cent were of grade I, 29 per cent of grade 2, 12 per cent of grade 3, and 20 per cent of grade 4. (TabIe III.) The stage of malignancy (Dukes, modified), recorded in sixty-two cases, was B in thirty and C in thirty-two. Metastasis to the Iiver occurred in forty
TABLE
II
TUMORS SIZE
3
OF OF
-
SMALL
INTESTINE:
PRIMARY
MALIGNANT
RECORDED
LESIONS
GRADE
Grade
:= ._ ._ ._ ._ -
e
__
_.
_.
__
-
i
OF
SMALL
(BRODERS)
INTESTINE:
OF LESIONS
I
Total
Malignnnt Lymphoma
III
TUMORS
t$zEnoma
Carcinoid
Malig*ant Lymphoma
Leiomyosarcoma
Total Misc. NO.
Per cent
‘I‘iirnors
PRIMARY
M.%LICNANT
TLXIOKS
01. (
of SrYl;ilI Intestine
SXIALL
“)s-
IKTIZSTINE:
cases, of which 62 per cent were carcinoid. PuImonary metastasis occurred in seven inPeritoneaI implantation and mesenstances. teric or omenta1 spread were observed in 47 per cent; regiona and distant Iymph nodes were invoIved in 44 per cent. Perineural i&Itration was rare. Contiguous organs were affected in fifty-two instances~- the &on, pancreas, appendix, urinary bIadder, ovaries, uterus and vagina. Extension to the abdomina1 waII occurred in nine. Surgical Measures and Results: SegmentaI resection was done in 173:cases. (TabIe IV.) Bypass procedures were empIoyed_in sixty cases. RadicaI resection--either WhippIe’s operation for duodenal malignancy or right hemicoIectomy for neoplasms in the termina1 ileum-was carried out in forty-eight instances. LocaI excision was seIected in thirteen cases, of which ten were carcinoid. OnIy expIoration and biopsy were attempted in thirty-three cases. The tumor was considered inopcrabIe in approximately 30 per cent of cases. PaIIiative surgery was done in 23 per cent. Irradiation suppIemented fifty-four operations, of which at Ieast thirty-four were for maIignant Iymphoma. CompIications foIIowing operation in seventyseven instances (24 per cent) were referabIe to aIimentary as we11 as extra-aIimentary Wound infection, CardiopuImonary causes. faiIure, peritonitis and thrombophIebitic phenomena accounted for 66 per cent of postoperative probIems. There were nineteen hospita1 deaths (6 per cent): six from peritonitis, six from cardio-
SURCIC4L
TECHNICS
EhlPLOYED
1961,
THKOLGH
puImonary CompIications, three from gastrointestina1 hemorrhage, two from vascuIar occiusion and two from shock. Inquiry (as of January 1963) was made regarding 229 patients who had been operated on five years earIier (1957) or before. Among the 215 patients traced (excluding hospital deaths), the over-a11 five year surviva1 was 35 per cent. (TabIe v.) Histopathologic Cutegories. HistopathoIogitally, four Iarge groups--adenocarcinoma, carcinoid, maIignant Iymphoma and Ieiomyosarcoma-accounted for a11 of the tumors except a miscellaneous category of about 7 per cent. (TabIe I.) Adenocarcinoma: The Iargest histopathoIogic group, adenocarcinomas amounted to 129 cases T ABLE IPRlhIARY
$-YEAR
*
RLALIGNAKT
SURVIVAL
TUMORS BY
OF
PATHOLOGIC
Inquiry as of January I, 1963 in 1957 or earlier; hospital deaths t Per cent of traced patients.
SMALL
INTESTINE:
CLASSIFICATION*
(includes patients excluded).
operated
on
PagtaIunan,
Mayo
or 39 per cent of the series. HaIf of them were in the jejunum and aImost a third in the duodenum. Fifty per cent were I to 5 cm. in diameter, none smalIer. MuItipIe independent adenocarcinomas were found in two cases. MaIignancy was of grade 2 in 43 per cent, of grade 4 in 24 per cent. Twenty-five tumors were of Dukes’ (modified) stage B and tweIve of stage C. The Iesion was obstructive, cIinicaIIy and radiographicaIIy, in at Ieast twenty-five cases, and perforating in fifteen. The tumor was considered inoperabIe in forty-six cases. PaIIiative operations were performed in forty-one cases. Liver metastasis was present in ten cases and Iung metastasis in four; the peIvic organs were affected in at Ieast seven. OnIy 22 per cent of the patients with adenocarcinoma survived five years after operation. Carcinoid: The second most common type, carcinoids were found in sixty-eight cases or 21 per cent. The iteum was the site of invoIvement in 85 per cent, the termina1 iIeum being especiaIIy often affected and sometimes the region of the iIeoceca1 vaIve. In three cases the Iesions occurred in diverticuIa of MeckeI’s type. Most carcinoids were I to 1.5 cm. in diameter; they constituted more than 40 per cent of a11 tumors in the range I to 5 cm. MaIignancy was of grade I in forty-eight of fifty cases with recorded grades. AII fifteen cIassified by Dukes’ (modified) system were assigned to stage C. Hepatic metastasis occurred in twenty-five cases (37 per cent). MuItiple independent primary carcinoids were found in nineteen cases. Despite their smaI1 size and Iow grade, the carcinoid tumors were inoperabIe in tweIve cases. OnIy paIIiative surgery was done in eIeven cases. GeneraIIy related to these decisions were Iiver metastasis in twenty-five cases (37 per cent), peritonea1 impIantation in thirty-three and Iymphatic spread in thirtyfive. Obstruction by kinking of the bowe1 was seen in at Ieast fifteen cases. The tumor was “functioning” in three. Five year postoperative surviva1 among forty-four traced patients was 52 per cent. Malignant Lymphoma: Of the sixty-one maIignant Iymphomas, 52 per cent were in the iIeum and 3g per cent. in the jejunum. The occurrence of subtypes compounded the difflcuIty of making an exact pathoIogic cIass& cation of malignant Iymphomatous tumors.
and Dockerty Like carcinoids, they tended to invoIve the termina1 part of the iIeum and the region of the iIeoceca1 vaIve. None was smaIIer than I cm. in diameter and 70 per cent were Iarger than 5 cm. An abdomina1 mass was paIpabIe on physica examination in 41 per cent of cases, AI1 of the fifteen Iymphomas graded for maIignancy were of grade 4. Five were Dukes’ (modified) stage B and five of stage C. MuItipIe independent primary Iymphomas were noted in nine cases. Metastasis affected the Iiver in one case and the Iungs in another. Mesenteric or omenta1 invoIvement occurred in gz per cent. The Iesion was inoperabIe in sixteen cases, and the operation was regarded as paIIiative in ten. The five year surviva1 rate of traced patients was 40 per cent. Leiomyosarcoma: The forty-seven Ieiomyosarcomas invoIved most often the jejunum (43 per cent) and the iIeum (34 per cent). In four cases the Iesions were found in diverticula of Meckel’s type. The tumor was partiaIIy exoenteric in five cases. The diameter was more than 5 cm. in 76 per cent. Despite their size, maIignancy was grade I in 53 per cent and grade 2 in 34 per cent. Severe bIeeding occurred in 55 per cent of cases. Lymphatic metastasis was not observed. The Iesion was considered inoperabIe in onIy three cases, and paIIiative resection was done in five others. Fifteen (48 per cent) of the thirty-one traced patients survived five or more years after operation. COMMENT
Hunt and assoFrequency and Selection. ciates [I] stated that onIy 3 to 6 per cent of gastrointestina1 neopIasms occur in the smaI1 bowel, despite its great Iength; but it is important that approximateIy 75 per cent of these tumors are maIignant. Among about 700 operations performed in 1960 at the Mayo CIinic for primary and secondary maIignancy of the stomach, smaI1 intestine, coIon and rectum, those invoIving the smaI1 intestine were approximateIy 4 per cent. Increased awareness of their possibihty and improved acuity in diagnosis have added significantIy to the number recognized at this cIinic in the past few years. Preoperative Diagnosis. Accurate preoperative diagnosis of smaI1 bowe1 maIignancy is achieved but seIdom. The rather insidious character of the pathoIogic process and the 16
Tumors
of Small
presence of associated conditions th:tt mask it5 true nature add to the inherent danger of the disease. This fact underscores the importance of aIertness to the vague initia1 signs and symptoms of intestina1 malignancy, such as weight Ioss, anorexia, ffatuIent dyspepsia and unexpIained anemia. Patients ordinarily seek medical attention because of fleing acutely or intractably symptomatic, but 35 per cent in this series told of having had the above compIaints for more than a year. The c.arcinoid syndrome, though diagnostic, is much Iess common than the tumor. Weber and Kirklin 121 remarked that the efficiency of rcJentgcnoIogic diagnosis decreases when the site of disease is shifted from the duodenum to the jejunum and ileum. The Iength and pliability of the small intestine and the unavoidable overlapping of the different segments were stated as natura1 reasons for this. RoentgenoIogic study, in the cases here reported, produced a diagnosis of malignant tumor in onIy 12 per cent and finding5 suggestive tif a lesion in 23 per cent, whiIe the intestinal series (barium swaIIon_) led to false negative interpretation in 7 per cent. Adenocarcinomas developing in the retroperitoneaI segment of the duodenum, as the> not LfrequentIy do, are estrcmely difficult to distinguish from primary carcinoma of the ampuIIa, pancreatic head or even the hcpatic fTexure. Histopathologic Appraisal. In discussing carcinoma of the jejunum and iIeum, Pridgcn 131 stated that adenocarcinomas of the small intestine arc about I per cent of gastrointestinal carcinomas. Hotsford and co-workers 141 commented that, whereas 60 per cent of intestinal sarcomas are Iocated in the sma1I intestine, primary adenocarcinoma of the small bowel is much less common than carcinoma of the large bowe1. In our series, sarcomntous lesions constituted nearly 34 per cent of neoplasms. Aside from Ieiomyosarcoma and malignant Iymphoma, they incIuded two instances of hemangioendotheIioma, one of IymphangioendotheIioma and one of fibromyxosarcoma. Detailed microscopic study of iIea1 carcino&k by Dockerty and Ashburn [5] gave e\-idence that carcinoid tumors are in essence peculiar Iow-grade carcinomas, and the investigators suggested that a11 such tumors be designated grade I adenocarcinoma (carcinoid). The nomencIature was devised to
Intestine
remind us of their malignant capabilities, slow evoIution and specific ceI1 type as distinguished from the ordinary tJ,pe of adenocarcinoma, which frequentIy is of much higher grade and consequentIy of more rapid growth and dissemination. hIuIticentricity of carcinoids in 25 to 50 per cent of cases has been reported, and in the present series muItipIe independent primar)tumors were present in 28 per cent. Starr [6] has offered a detailed discussion of smal1 bowe1 leiomyosarcoma in his thesis reporting forty-one cases (some of which are incIuded in this series). The tendency of these tumors to be low-grade and radioresistant, and to bleed and to spread via the bloodstream was emphasized. Ewluded Cases. Among those casesexcIudec1 from this study were twenty-eight smaI1 bowel Iesions considered metastatic from suspected primary tumors elsewhere. Adenocarcinoma had metastasized from the large intestine in eIeven cases, the pancreas in three, the ampulla of Vater in three and the stomach in one. A squamous ceI1 epitheIioma evidently had spread from cancer of the cervix in one patient, and from a lesion in a Tong-standing abdomina1 fistula in another. Adenoacanthoma, aIso from the cervix, was encountered in one case. Of three patients with extensive malignant process in the retroperitonea1 region, one each had reticulum ceI1 sarcoma, lymphosarcoma and IymphobIastoma. The primary lesion in four cases could not be determined exactly, aIthough the lung, thyroid, ovary and finger (melanoma) were suspected to be the sources. SUMMARY
AND
CONCLUSIONS
Review was made of 327 surgical cases of primary malignant tumors in the smaI1 intestine covering a twenty-live year period at the k,layo CIinic. The annual frequency increased in the Iast seven years. Adenocarcinoma, type ordinaire, accounted for 39 per cent of the series, and patients aMicted with this tumor had the poorest five year surviva1 rate (22 per cent). Adenocarcinema, carcinoid type, formed 21 per cent of the tota group and the five year survival rate, as expected, was the highest (52 per cent). MaIignant Iymphomas comprised 19 per cent of the tota group, and 40 per cent of the
Pagtahnan,
Mayo and Dockerty
patients with this growth survived five or more years postoperativeIy. Leiomyosarcoma made up 14 per cent, with 48 per cent of patients surviving five or more years. A misceIIaneous group constituted 7 per cent. Among the 215 traced patients, the over-a11 figure for five year surviva1 after definitive or paIIiative surgery was 35 per cent. EarIy and accurate diagnosis of smaI1 bowel tumors is seIdom achieved because of the rarity of this disease, its insidious nature, the symptomatic simiIarity to other abdomina1 conditions, and the diffIcuIty of demonstrating the underIying pathoIogic condition radioIogicaIIy. Each pathoIogic group of smaI1 bowe1 tumors has its specia1 prognosis-hopefu1 or grave. If a smaI1 bowe1 tumor is considered in a11 probIems of abdomina1 pain or gastrointestina1 bIeeding, such a diagnosis may be made earIy enough for a favorabIe outIook. UnfortunateIy, the onset of obstructive phenomena or the syndrome of the acute abdomen often indicates
that the tumor aIready has progressed the stage of surgica1 cure.
beyond
REFERENCES I. HUNT, W. H., III, BRODERS, A. C., JR. and HIGHTOWER, N. C., JR. Primary neopIaslns of the smaII bowe1: a report of 81 cases. South. M. .I.. 31: 482, 1958. 2. WEBER, H. M. and KIRKLIN, B. R. RoentgenoIogic manifestations of tumors of the smaI1 intestine. Am. J. Roentgenol., 47: 243, 1942. 1. PRIDGEN. J. E. Carcinoma of the Jeiunum and IIeum .ExcIusive of Carcinoid. Thesis, Graduate SchooI, University of Minnesota, 1949. 4. BOTSFORD,T. W., CROWE, P. and CROCKER, D. W. Tumors of the smaI1 intestine: a review of experience with 115 cases incIuding a report of a rare case of maIignant hemangio-endotheIioma. Am. J. Surg., 103: 358, 1962. 5. DOCKERTY, M. B. and ASHBURN, F. S. Carcinoid tumors (so-caIIed) of the iIeum: report of 13 cases in which there was metastasis. Arch. Surg., 47: 221, 1943. 6. STARR, G. F. Myomatous Tumors of the SmaII Intestine, Benign, and MaIignant. Thesis, Graduate SchooI, University of Minnesota, 1953.
Reprinted from the July issue of The American Journal of Surgery. A Yorke Medical Journal. Published by Technical Publishing Company, A Division of Dun-Donnelley Publishing Corporation, a Dun & Bradstreet Co., 666 Fifth Avenue, New York, N.Y. 10103. Copyright 1964. All rights reserved. Printed in the U.S.A.
KEDENTCIR
T two
Malignant Tumors Small Intestine
.1.G. PAGTALLxAK,
nr.D., CHARLES \\-.Y~1.41.0, M.D. AND Rochester, 2\linnesota
STOMACH and
AIATEKIAL AND
METHODS
Kevielv was made of the records oft he 370 hIayo Clinic patients having malignant tumor of the smaI1 intc.stinc in the twenty-five year period, 1037 through 1961. The resected specimens wcrc siudicd and forty-three wcrc excluded from this series: tncnty-eight secondary, elel en rccurrcnt and four incidental tumors. The 327 cases remaining after exclusion formed the basis of this invcstigation. Clinical, laboratory, surgical and pathologic aspects of these cast’s were reviewed and inquir>was msdt as to survival after operation. FINDINGS
and Distribution: From operations for primary mabgnant lesions of the smaI1 bowel at the Mayo Chic averaged about eIeven per year; but from 1955 through 1961, the average was eighteen. Thus about 25 per cent of the tumors studied were excised in the fI\-e years 1953 through 1939, and about I_C per cent in the last t\yo scars covered. The distribution of patients by age and sey followed the pattern generally associated with General.
1937
through
~IALCOLM
B. DOCKERT\-,
M.D.,
malignant growths in the stomach, colon and other organs. An abrupt increase in number iiJlt,Lved the fourth decade of life, and the greatest frequency (3-j per cent) was in the sisth decade. The patients ranged from twenty months to tight!--three years in age, with a mean of Iilt~.-& years. There were 207 males, predominating c,v& females by a ratio of I.;: I. Diagnostic Data: Thirty-four per cent of the patients had develupecl symptoms and signs less than six months before operation, 31 per cent \I-ithin six to twelve months of it, and 3 per cent mot-c than five \-cars preoperativelq. Abdominal pain (213 cases) and Ioss of weight (I 39 cases) were the most common complaint>. The pain was dcacribed uauaIly as intermittent or crampy. Vomiting (103 cases) often occurred earIv in the course. Bowel dysfunction (ninety-k cascb) occurred as diarrhea or constipation; gastrointestinal bkcding (eight)--live casesj was mosti>- in the form ()I’ mcIena. Vague and general complaints wcrc present in a significant number cjf casts: flatulent tlyspt’psia in sist\--one, ilnoresia in forty-eight, anemia in thirty-five, and jaundice in eight. An abdominal mass was palpated in ninety -severs patients; varying degrees of tenderness xere found in fort\--nine, n.nd abdominal cli5tention in twenty-nine. In many case>, complaints due to small bowe1 mnlignanc> sinlulated those of peptic, choIecystic or pancreatic disease, suggesting diflieuity in the upper part of the abdomen; in uthcrs the symptoms mimicked cnterocolitis or diverticulitis, suggesting a more dista1 pathologic process. Presented often was the problem of indeterminate tumor or indeterminate gastrointestinal bleeding. R:tdiologicaIl~, the lesion was interpreted as obstructive in most cases and ulcerative, poly-
the large intestine are \‘ery common sites for development ol’ primary malignant disease. By contrast, malignant neopIasms of the small primary intestine are so rare that their diagnosis often is made by exclusion. This does not promote early dixgnosis with increased opportunity for cure. The foIIowing report is designed to emphasize the clinica and pathologic features, as well x the prognostic implications, in a sizable series of patients with primary maIignancy of the small intestine. HE
of the
Incidence
195-1,
I3
Amel-ica?z JournalofSurgery, Volume
108, Jul\
1064
Pagtahnan, PRIMARY
MALIGNANT
TUMORS
OF
Mayo
and Dockerty
TABLE
I
SMALL
INTESTINE:
PATHOLOGIC I
___ -.__ Duodenum..... Jeiunum..
i
_____
__I_.-._
65
.
-+:+-
22
Total..
LOCATION
AND
)
.t.
58
32
I
6
4
129
68
1
61
16
2
7. /
47
(
poid or intussusceptive in others. The radioIogist diagnosed a carcinomatous lesion in thirty-nine cases, obstructive tumor in thirtyseven and dilated Ioops of bowe1 in eIeven. The smaI1 bowe1 series (barium swaIIow) indicated no abnormaIity in twenty-two instances. Preoperative laboratory studies reveaIed that seventy patients (21 per cent) had a hemogIobin concentration of Iess than IO gm. per IOO ml. of bIood and erythrocyte sedimentation was:greater than Ig mm. in one hour (Westergren) in 66 per cent of the cases in which it was determined. The three most common associated conditions were diverticuIa in thirty-six cases, peptic uIcer in twenty-eight and gaIIbIadder disease in twenty-five. Pathology: The iIeum was the site of 41 per cent of the neopIasms, the jejunum of 36 per cent and the duodenum of 18 per cent. The site of 5 per cent was not specified. (TabIe I.) TABLE PRIMARY MALIGNANT RECORDED
Size (cm.)
BY
41
_(
_.__ Ilrum. ~~ Unspecified.,
-_-
I
DISTKIBUTION
TYPE
Ade?o‘,“di
---
Carci_
noid
-I-
Of the 244 Iesions whose size was recorded, 50 per cent had diameters in the range of I to 5 cm. and 48 per cent were larger. OnIy five tumors were smaIIer than I cm. (TabIe II.) The growths were described as uIcerative in 105 cases, annuIar in sixty-eight and poIypoid in twenty-two. They were perforating in twenty-two cases and intussuscepting in ten. Cavitation and interna fistula were observed in eight cases (Ieiomyosarcoma). Two specimens (maIignant Iymphoma) were aneurysmal in appearance. Among the 249 Iesions whose grade of maIignancy (Broders) was recorded, 38 per cent were of grade I, 29 per cent of grade 2, 12 per cent of grade 3, and 20 per cent of grade 4. (TabIe III.) The stage of malignancy (Dukes, modified), recorded in sixty-two cases, was B in thirty and C in thirty-two. Metastasis to the Iiver occurred in forty
TABLE
II
TUMORS SIZE
3
OF OF
-
SMALL
INTESTINE:
PRIMARY
MALIGNANT
RECORDED
LESIONS
GRADE
Grade
:= ._ ._ ._ ._ -
e
__
_.
_.
__
-
i
OF
SMALL
(BRODERS)
INTESTINE:
OF LESIONS
I
Total
Malignnnt Lymphoma
III
TUMORS
t$zEnoma
Carcinoid
Malig*ant Lymphoma
Leiomyosarcoma
Total Misc. NO.
Per cent
‘I‘iirnors
PRIMARY
M.%LICNANT
TLXIOKS
01. (
of SrYl;ilI Intestine
SXIALL
“)s-
IKTIZSTINE:
cases, of which 62 per cent were carcinoid. PuImonary metastasis occurred in seven inPeritoneaI implantation and mesenstances. teric or omenta1 spread were observed in 47 per cent; regiona and distant Iymph nodes were invoIved in 44 per cent. Perineural i&Itration was rare. Contiguous organs were affected in fifty-two instances~- the &on, pancreas, appendix, urinary bIadder, ovaries, uterus and vagina. Extension to the abdomina1 waII occurred in nine. Surgical Measures and Results: SegmentaI resection was done in 173:cases. (TabIe IV.) Bypass procedures were empIoyed_in sixty cases. RadicaI resection--either WhippIe’s operation for duodenal malignancy or right hemicoIectomy for neoplasms in the termina1 ileum-was carried out in forty-eight instances. LocaI excision was seIected in thirteen cases, of which ten were carcinoid. OnIy expIoration and biopsy were attempted in thirty-three cases. The tumor was considered inopcrabIe in approximately 30 per cent of cases. PaIIiative surgery was done in 23 per cent. Irradiation suppIemented fifty-four operations, of which at Ieast thirty-four were for maIignant Iymphoma. CompIications foIIowing operation in seventyseven instances (24 per cent) were referabIe to aIimentary as we11 as extra-aIimentary Wound infection, CardiopuImonary causes. faiIure, peritonitis and thrombophIebitic phenomena accounted for 66 per cent of postoperative probIems. There were nineteen hospita1 deaths (6 per cent): six from peritonitis, six from cardio-
SURCIC4L
TECHNICS
EhlPLOYED
1961,
THKOLGH
puImonary CompIications, three from gastrointestina1 hemorrhage, two from vascuIar occiusion and two from shock. Inquiry (as of January 1963) was made regarding 229 patients who had been operated on five years earIier (1957) or before. Among the 215 patients traced (excluding hospital deaths), the over-a11 five year surviva1 was 35 per cent. (TabIe v.) Histopathologic Cutegories. HistopathoIogitally, four Iarge groups--adenocarcinoma, carcinoid, maIignant Iymphoma and Ieiomyosarcoma-accounted for a11 of the tumors except a miscellaneous category of about 7 per cent. (TabIe I.) Adenocarcinoma: The Iargest histopathoIogic group, adenocarcinomas amounted to 129 cases T ABLE IPRlhIARY
$-YEAR
*
RLALIGNAKT
SURVIVAL
TUMORS BY
OF
PATHOLOGIC
Inquiry as of January I, 1963 in 1957 or earlier; hospital deaths t Per cent of traced patients.
SMALL
INTESTINE:
CLASSIFICATION*
(includes patients excluded).
operated
on
PagtaIunan,
Mayo
or 39 per cent of the series. HaIf of them were in the jejunum and aImost a third in the duodenum. Fifty per cent were I to 5 cm. in diameter, none smalIer. MuItipIe independent adenocarcinomas were found in two cases. MaIignancy was of grade 2 in 43 per cent, of grade 4 in 24 per cent. Twenty-five tumors were of Dukes’ (modified) stage B and tweIve of stage C. The Iesion was obstructive, cIinicaIIy and radiographicaIIy, in at Ieast twenty-five cases, and perforating in fifteen. The tumor was considered inoperabIe in forty-six cases. PaIIiative operations were performed in forty-one cases. Liver metastasis was present in ten cases and Iung metastasis in four; the peIvic organs were affected in at Ieast seven. OnIy 22 per cent of the patients with adenocarcinoma survived five years after operation. Carcinoid: The second most common type, carcinoids were found in sixty-eight cases or 21 per cent. The iteum was the site of invoIvement in 85 per cent, the termina1 iIeum being especiaIIy often affected and sometimes the region of the iIeoceca1 vaIve. In three cases the Iesions occurred in diverticuIa of MeckeI’s type. Most carcinoids were I to 1.5 cm. in diameter; they constituted more than 40 per cent of a11 tumors in the range I to 5 cm. MaIignancy was of grade I in forty-eight of fifty cases with recorded grades. AII fifteen cIassified by Dukes’ (modified) system were assigned to stage C. Hepatic metastasis occurred in twenty-five cases (37 per cent). MuItiple independent primary carcinoids were found in nineteen cases. Despite their smaI1 size and Iow grade, the carcinoid tumors were inoperabIe in tweIve cases. OnIy paIIiative surgery was done in eIeven cases. GeneraIIy related to these decisions were Iiver metastasis in twenty-five cases (37 per cent), peritonea1 impIantation in thirty-three and Iymphatic spread in thirtyfive. Obstruction by kinking of the bowe1 was seen in at Ieast fifteen cases. The tumor was “functioning” in three. Five year postoperative surviva1 among forty-four traced patients was 52 per cent. Malignant Lymphoma: Of the sixty-one maIignant Iymphomas, 52 per cent were in the iIeum and 3g per cent. in the jejunum. The occurrence of subtypes compounded the difflcuIty of making an exact pathoIogic cIass& cation of malignant Iymphomatous tumors.
and Dockerty Like carcinoids, they tended to invoIve the termina1 part of the iIeum and the region of the iIeoceca1 vaIve. None was smaIIer than I cm. in diameter and 70 per cent were Iarger than 5 cm. An abdomina1 mass was paIpabIe on physica examination in 41 per cent of cases, AI1 of the fifteen Iymphomas graded for maIignancy were of grade 4. Five were Dukes’ (modified) stage B and five of stage C. MuItipIe independent primary Iymphomas were noted in nine cases. Metastasis affected the Iiver in one case and the Iungs in another. Mesenteric or omenta1 invoIvement occurred in gz per cent. The Iesion was inoperabIe in sixteen cases, and the operation was regarded as paIIiative in ten. The five year surviva1 rate of traced patients was 40 per cent. Leiomyosarcoma: The forty-seven Ieiomyosarcomas invoIved most often the jejunum (43 per cent) and the iIeum (34 per cent). In four cases the Iesions were found in diverticula of Meckel’s type. The tumor was partiaIIy exoenteric in five cases. The diameter was more than 5 cm. in 76 per cent. Despite their size, maIignancy was grade I in 53 per cent and grade 2 in 34 per cent. Severe bIeeding occurred in 55 per cent of cases. Lymphatic metastasis was not observed. The Iesion was considered inoperabIe in onIy three cases, and paIIiative resection was done in five others. Fifteen (48 per cent) of the thirty-one traced patients survived five or more years after operation. COMMENT
Hunt and assoFrequency and Selection. ciates [I] stated that onIy 3 to 6 per cent of gastrointestina1 neopIasms occur in the smaI1 bowel, despite its great Iength; but it is important that approximateIy 75 per cent of these tumors are maIignant. Among about 700 operations performed in 1960 at the Mayo CIinic for primary and secondary maIignancy of the stomach, smaI1 intestine, coIon and rectum, those invoIving the smaI1 intestine were approximateIy 4 per cent. Increased awareness of their possibihty and improved acuity in diagnosis have added significantIy to the number recognized at this cIinic in the past few years. Preoperative Diagnosis. Accurate preoperative diagnosis of smaI1 bowe1 maIignancy is achieved but seIdom. The rather insidious character of the pathoIogic process and the 16
Tumors
of Small
presence of associated conditions th:tt mask it5 true nature add to the inherent danger of the disease. This fact underscores the importance of aIertness to the vague initia1 signs and symptoms of intestina1 malignancy, such as weight Ioss, anorexia, ffatuIent dyspepsia and unexpIained anemia. Patients ordinarily seek medical attention because of fleing acutely or intractably symptomatic, but 35 per cent in this series told of having had the above compIaints for more than a year. The c.arcinoid syndrome, though diagnostic, is much Iess common than the tumor. Weber and Kirklin 121 remarked that the efficiency of rcJentgcnoIogic diagnosis decreases when the site of disease is shifted from the duodenum to the jejunum and ileum. The Iength and pliability of the small intestine and the unavoidable overlapping of the different segments were stated as natura1 reasons for this. RoentgenoIogic study, in the cases here reported, produced a diagnosis of malignant tumor in onIy 12 per cent and finding5 suggestive tif a lesion in 23 per cent, whiIe the intestinal series (barium swaIIon_) led to false negative interpretation in 7 per cent. Adenocarcinomas developing in the retroperitoneaI segment of the duodenum, as the> not LfrequentIy do, are estrcmely difficult to distinguish from primary carcinoma of the ampuIIa, pancreatic head or even the hcpatic fTexure. Histopathologic Appraisal. In discussing carcinoma of the jejunum and iIeum, Pridgcn 131 stated that adenocarcinomas of the small intestine arc about I per cent of gastrointestinal carcinomas. Hotsford and co-workers 141 commented that, whereas 60 per cent of intestinal sarcomas are Iocated in the sma1I intestine, primary adenocarcinoma of the small bowel is much less common than carcinoma of the large bowe1. In our series, sarcomntous lesions constituted nearly 34 per cent of neoplasms. Aside from Ieiomyosarcoma and malignant Iymphoma, they incIuded two instances of hemangioendotheIioma, one of IymphangioendotheIioma and one of fibromyxosarcoma. Detailed microscopic study of iIea1 carcino&k by Dockerty and Ashburn [5] gave e\-idence that carcinoid tumors are in essence peculiar Iow-grade carcinomas, and the investigators suggested that a11 such tumors be designated grade I adenocarcinoma (carcinoid). The nomencIature was devised to
Intestine
remind us of their malignant capabilities, slow evoIution and specific ceI1 type as distinguished from the ordinary tJ,pe of adenocarcinoma, which frequentIy is of much higher grade and consequentIy of more rapid growth and dissemination. hIuIticentricity of carcinoids in 25 to 50 per cent of cases has been reported, and in the present series muItipIe independent primar)tumors were present in 28 per cent. Starr [6] has offered a detailed discussion of smal1 bowe1 leiomyosarcoma in his thesis reporting forty-one cases (some of which are incIuded in this series). The tendency of these tumors to be low-grade and radioresistant, and to bleed and to spread via the bloodstream was emphasized. Ewluded Cases. Among those casesexcIudec1 from this study were twenty-eight smaI1 bowel Iesions considered metastatic from suspected primary tumors elsewhere. Adenocarcinoma had metastasized from the large intestine in eIeven cases, the pancreas in three, the ampulla of Vater in three and the stomach in one. A squamous ceI1 epitheIioma evidently had spread from cancer of the cervix in one patient, and from a lesion in a Tong-standing abdomina1 fistula in another. Adenoacanthoma, aIso from the cervix, was encountered in one case. Of three patients with extensive malignant process in the retroperitonea1 region, one each had reticulum ceI1 sarcoma, lymphosarcoma and IymphobIastoma. The primary lesion in four cases could not be determined exactly, aIthough the lung, thyroid, ovary and finger (melanoma) were suspected to be the sources. SUMMARY
AND
CONCLUSIONS
Review was made of 327 surgical cases of primary malignant tumors in the smaI1 intestine covering a twenty-live year period at the k,layo CIinic. The annual frequency increased in the Iast seven years. Adenocarcinoma, type ordinaire, accounted for 39 per cent of the series, and patients aMicted with this tumor had the poorest five year surviva1 rate (22 per cent). Adenocarcinema, carcinoid type, formed 21 per cent of the tota group and the five year survival rate, as expected, was the highest (52 per cent). MaIignant Iymphomas comprised 19 per cent of the tota group, and 40 per cent of the
Pagtahnan,
Mayo and Dockerty
patients with this growth survived five or more years postoperativeIy. Leiomyosarcoma made up 14 per cent, with 48 per cent of patients surviving five or more years. A misceIIaneous group constituted 7 per cent. Among the 215 traced patients, the over-a11 figure for five year surviva1 after definitive or paIIiative surgery was 35 per cent. EarIy and accurate diagnosis of smaI1 bowel tumors is seIdom achieved because of the rarity of this disease, its insidious nature, the symptomatic simiIarity to other abdomina1 conditions, and the diffIcuIty of demonstrating the underIying pathoIogic condition radioIogicaIIy. Each pathoIogic group of smaI1 bowe1 tumors has its specia1 prognosis-hopefu1 or grave. If a smaI1 bowe1 tumor is considered in a11 probIems of abdomina1 pain or gastrointestina1 bIeeding, such a diagnosis may be made earIy enough for a favorabIe outIook. UnfortunateIy, the onset of obstructive phenomena or the syndrome of the acute abdomen often indicates
that the tumor aIready has progressed the stage of surgica1 cure.
beyond
REFERENCES I. HUNT, W. H., III, BRODERS, A. C., JR. and HIGHTOWER, N. C., JR. Primary neopIaslns of the smaII bowe1: a report of 81 cases. South. M. .I.. 31: 482, 1958. 2. WEBER, H. M. and KIRKLIN, B. R. RoentgenoIogic manifestations of tumors of the smaI1 intestine. Am. J. Roentgenol., 47: 243, 1942. 1. PRIDGEN. J. E. Carcinoma of the Jeiunum and IIeum .ExcIusive of Carcinoid. Thesis, Graduate SchooI, University of Minnesota, 1949. 4. BOTSFORD,T. W., CROWE, P. and CROCKER, D. W. Tumors of the smaI1 intestine: a review of experience with 115 cases incIuding a report of a rare case of maIignant hemangio-endotheIioma. Am. J. Surg., 103: 358, 1962. 5. DOCKERTY, M. B. and ASHBURN, F. S. Carcinoid tumors (so-caIIed) of the iIeum: report of 13 cases in which there was metastasis. Arch. Surg., 47: 221, 1943. 6. STARR, G. F. Myomatous Tumors of the SmaII Intestine, Benign, and MaIignant. Thesis, Graduate SchooI, University of Minnesota, 1953.
Reprinted from the July issue of The American Journal of Surgery. A Yorke Medical Journal. Published by Technical Publishing Company, A Division of Dun-Donnelley Publishing Corporation, a Dun & Bradstreet Co., 666 Fifth Avenue, New York, N.Y. 10103. Copyright 1964. All rights reserved. Printed in the U.S.A.