Lung Resection for Colorectal
Metastases
10-Year Results Patricia M.
McCormack, MD; Michael E. Burt, MD, PhD; Manjit S. Bains, MD; Nael Martini, MD; Valerie W. Rusch, MD; Robert J. Ginsberg, MD
Background.\p=m-\Metastasectomyfor colorectal carcinoma lung is controversial. We analyzed results of this approach to justify its credibility. Methods.\p=m-\Westudied 144 patients by retrospective review after complete resection of lung metastases from colorectal cancer from 1965 through 1988. Patient selection and prognostic factors influencing survival were analyzed. Survival was analyzed by the Kaplan-Meier method, and comparisons were made by log-rank analysis. Results.\p=m-\Atotal of 170 thoracotomies were performed in 144 patients. The overall 5- and 10-year survival was 40% and 30%, respectively. Those patients undergoing complete resection of their metastases survived significantly longer than those undergoing incomplete resections. Conclusion.\p=m-\Itappears that resection of pulmonary metastases from colorectal carcinoma translates into long\x=req-\ \s=b\
to the
term survival benefit.
(Arch Surg. 1992;127:1403-1406) of the
first successful metastasectomy, by report Churchill2 The vis,1 appeared 1939, Barney first successful of recorded Di¬ and the case in an American journal a long-term survival after nephrectomy and pulmonary lobectomy for metastatic renal cell carcinoma. According to Blister et al,3 Blalock recorded the first resection of a colorectal metastasis to the lung in 1944. For the next two decades, progress was slow. Case selection was limited to patients in whom a lung lesion appeared well after the primary was removed, or to patients with only one lung lesion or, in rare cases, two le¬ sions situated in the same lung. The surgical approach to metastatic tumors to the lungs was justified by the improved survival statistics for sar¬ coma primary tumors.4"7 Application of this approach to primary carcinomas has followed more cautiously. The second most common cancer in the United States is colorectal carcinoma. Thirty percent of these patients in 1927. In
1992. From the Thoracic Service, Department of Surgery, Memorial Sloan\x=req-\ Kettering Cancer Center, New York, NY. Presented at the 45th Annual Cancer Symposium of the Society of Surgical Oncology, New York, NY, March 17, 1992. Reprint requests to Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021 (Dr McCormack).
Accepted for publication August 8,
present with advanced disease and
are incurable. Of the remainder who undergo curative colon resections, nearly half develop recurrent cancer.8 Twenty percent of recurrent cancers are located in the lungs, as well as other sites in the body.9,10 Yet, only 2% to 4% of patients with primary colorectal carcinoma have métastases only in the lungs after a curative resection.11,12 This select group of patients is targeted for this report.
PATIENTS AND METHODS At Memorial Sloan-Kettering Cancer Center, New York, NY a retrospective review was undertaken of the patients who under¬ went resection of pulmonary métastases from primary colorectal carcinomas between 1965 and 1988. The charts of 144 patients were analyzed; there were 55 women and 89 men. Ages ranged from 26 to 83 years. In a majority of the cases, the lesions appeared between the fifth and seventh decades of life, the incidence in the men peaking 10 years later than that in the women. Follow-up was possible in all but four patients. All four were free of disease 2 to 5 years after surgery. In 16 charts, the primary surgery had been performed else¬ where, and no data were available as to staging. Before pulmonary resection, the extent of disease was carefully evaluated to be certain there was no disease elsewhere in the body. The liver, in particular, was free of disease. All the patients fit the criteria established as prerequisites for lung resection for metastatic disease. There was no tumor elsewhere, no better therapy was available, and complete resection was possible. Pul¬ monary function tests, including diffusion capacity and arterial blood gases, were performed in all candidates. If test results showed that the pulmonary resection required to remove all dis¬ ease would still leave sufficient lung tissue for daily activities, this was judged to be adequate. In this study, survival time was calculated from the date of the pulmonary resection. Survival was calculated by the Kaplan-Meier method, and all comparisons were done by logrank analysis.
RESULTS Métastases were limited to one lung in 83% (120/144) of these patients. In 55% (80/144) of the patients, there was a single lesion. Of the 17% (24/144) with bilateral lesions, two patients had a single lesion in each lung, while the re¬ mainder had multiple bilateral métastases. One hundred seventy thoracotomies were performed in these 144 patients. Simultaneous bilateral metastasectomies were performed via sternotomies in 16 patients. The
Downloaded From: http://archsurg.jamanetwork.com/ by a New York University User on 06/05/2015
1001
loo
jet
80 80 "
Ht
60
.5
40
à
"^S /^X
40
>1
-
0
12
24
36
48
60
Time,
Fig 1.—Overall survival rate at 5 and
72
84
96
108
10 years (N=144).
lung.
Eleven patients could not have a complete resection be¬ of borderline pulmonary reserve. These patients had implantation of iodine 131 in the unresectable residual tu¬ mor. The median survival of these patients was nine months (range, 2 to 18 months), with all patients dying of progressive disease. There were no perioperative deaths, and three patients experienced morbidity (two patients had prolonged air leak and one had arrhythmia). Pathologic evaluation of the primary colorectal cancer showed Dukes stage C in 64 patients, Dukes stage B in 42 patients, and Dukes stage A in 17 patients. Four patients had squamous cell carcinoma of the rectum, one had cloacagenie tumor, and in 16 patients adenocarcinomas could not be staged because surgery had been done elsewhere and no data were available. The interval from resection of the primary tumor to re¬ section of the lung métastases is described as the diseasefree interval (DFI). Seventeen patients presented with pri¬ mary and metastatic disease simultaneously. Eighteen patients developed lung lesions within 1 year of treatment of the primary cancer. The remaining 109 patients devel¬ oped pulmonary métastases more than 1 year after resec¬ tion of the colorectal primary. The overall survival rate calculated by the Kaplan-Meier method was 44% at five years and 26% at 10 years (Fig 1). The prognostic indicators for survival analysis most of¬ ten mentioned in the literature are the number of resected nodules, the DFI, and the site or stage of the primary tu¬ mor. The majority of these patients (80/144) presented with a solitary lung lesion. One lesion in each lung was cause
in just two patients. Forty patients presented multiple lesions limited to one lung, while the remaining 22 patients had multiple bilateral lesions.
with
seen
12
24
36
Time,
Fig 2.—Number of nodules were not significant.
vs
72
60
48
mo
volume of lung removed was related to the location of the tumor. Complete resection was a prerequisite for good re¬ sults. Thirty-four lobectomies were required, where tumor location precluded a lesser resection. Wedge resection was the most common procedure (97/170). In instances where the patient had bilateral lesions, the approach was dictated by pulmonary reserve and location of lesions. Staged posterolateral thoracotomies during a single hospital stay allowed the best exposure to each lung for posterior lesions or lesions in the left lower lobe. Me¬ dian sternotomy was used more frequently when the lesions were few and anteriorly situated.13 A transverse sternotomy with bilateral anterior thoracotomies probably offers the best simultaneous approach to all aspects of each
rare,
0
120
(N=80)
~^~~~~~H-1-h
20
20
1 Nodule
i,
'
84
Nodule (N=64) 96
108
120
mo
survival at 5 and 10 years. Differences
100
Synchronous (N=1 7) Metachronous, 1 y (N=109)
80
12
24
36
48
60
Time,
72
84
96
108 120
mo
Fig 3.—Survival according to disease-free interval from primary colon resection to metastasectomy. Differences were not significant. Studies have shown that computed tomographic scan¬ nodules in the ning has the highest yield for lung parenchyma, being able to locate a 3-mm lesion. However, as proved by Chang et al,14 the accuracy in identifying malignant nodules is just 45%. An abnormal lesion seen on a chest roentgenogram has a 90% specific¬ ity, and a plane tomogram is 70% accurate for malignant neoplasms. Serial computed tomographic scans are now recommended as being both more specific and more sen¬ sitive in detecting significant pulmonary métastases.15 Figure 2 shows that there was no statistically significant difference in survival between patients with one or more than one completely resected pulmonary metastasis. Patients were divided into three groups according to DFI: those presenting with lung metastasis simultaneously with the primary colorectal tumor, those in whom the DFI was 12 months or less, and those whose DFI was more than 1 year. Figure 3 shows no survival advantage among these three groups. Analysis with respect to survival among the 123 tumors that could be staged is shown in Fig 4. There was neither a trend nor a difference among Dukes stages A, B, and C either at 5 or at 10 years. A combination of two indicators, namely, number of nodules and DFI, was compared by log-rank analysis. The comparison showed a trend for solitary lesions with a short DFI to have a better 5-year survival than multiple nodules
Downloaded From: http://archsurg.jamanetwork.com/ by a New York University User on 06/05/2015
identifying
lOOt-K 80 -
1^
Multiple, >1 y (N=45) Multiple, 1 y (N=64) Solitary, ^,
%^\
60
40
T
\ v~*1—v~-'A
mil
"
-1
iV
0
12
24
36
48
60
Time,
72
84
¡
B
XC
20-
96
108 120 48
mo
60
Time,
Fig 4.—Dûtes stages A (N=17), B (N=42), analysis. Differences were not significant.
108
72
120
mo
and C (N=64), and survival
Fig 5.—Number of nodules vs disease-free interval and survival pattern.
with a long DFI. At 10 years, this difference did not reach statistical significance (Fig 5).
Five-Year Survival After Resection of Métastases From Colorectal Primary Tumors
COMMENT Colorectal carcinoma remains the second most common visceral cancer in the nation in both incidence and deaths. Concerted efforts have been made with all treatment mo¬ dalities to improve the survival rate in these patients. Ra¬ diation therapy delivered preoperatively to postoperatively may decrease the incidence of local recurrence, and lead to somewhat longer survival.1619 Adjuvant chemo¬ therapy either as a single drug or in combination in randomized controlled trials has not, in general, offered any significant survival benefit.20"24 Patients with untreated state IV colorectal carcinoma live for 8 to 24 months. There is no significant 5-year sur¬ vival rate in treatment of the primary tumor or its recur¬ rences by any treatment modality other than surgery. Of all patients with curative resections, 10% to 20% will develop pulmonary métastases. Ten percent of these will have the lung as the sole metastatic site. Therefore, we an¬ alyzed a very select subsegment of all patients with colo¬ rectal carcinoma.8 The diagnosis is suspected initially most often when a chest roentgenogram is taken for another purpose, since these lesions produce no symptoms. Detection of a new solitary pulmonary nodule is not diagnostic of colorectal métastases. A benign lesion or a new lung primary lesion is a frequent occurrence, and diagnosis is essential.25 Computed tomographic scans clarify the status of the primary site and the presence or absence of intraabdominal recurrence or hepatic métastases. Colonoscopy verifies the condition of the anastomotic site. When there is no disease below the diaphragm, the respiratory func¬ tion of the patient is assessed. If the lung status will allow the required resection, this option for therapy should be offered to the patient. The operative procedure had no mortality and a very low morbidity in this study. This select group can achieve a 44% survival at 5 years and a 26% survival at 10 years, if the lung lesions are re¬ sected. Suitable candidates can be readily chosen from the group presenting with advanced lesions. A review of the literature9,12,2529 showed that this study compared favor¬ ably with other published series (Table). There is considerable variation to date regarding the use of prognostic variables in selecting candidates who are
Source, y Cahanetal,25 1974 Vincent et al,26 1978 Wilkins et al,28 1978 Mountain et al,29 1978 McCormackand Attiyeh,12 1979
al,29 1980 Goya et al,9 1989 »Rectal, 57%; colon, 0%. Morrow et
No. of Patients
% Survival
31
30
13
31*
34
28
28
28
35
22
16
13
65
41
most likely to benefit from this surgery. The analysis of the current data confirmed this finding. There are two contraindications to surgery: (1) insuffi¬ cient pulmonary reserve to accomplish a complete resec¬ tion; an incomplete resection results in a low rate of sur¬
vival; and (2) a "shower" of métastases, ie, a presentation of tiny nodules throughout the lung parenchyma, thus de¬ noting microscopic disease as well as macroscopic. In this
not possible. Such a presenta¬ usually be seen on a good-quality computed tomographic scan but will occasionally be a surprise find¬ ing at thoracotomy. Colorectal carcinoma métastases to the lung historically are usually few in number and have a relatively slow dou¬ bling time. This makes resection possible in the majority of
situation, total resection is tion
can
instances.262*
CONCLUSIONS of the data from 144 patients who had resection Analysis of pulmonary métastases from colorectal primary carci¬ noma showed a 44% survival rate at 5 years and 26% at 10 years. Neither the DFI, the number of nodules at presen¬ tation, nor the state of the primary colorectal cancer signif¬ icantly altered survival rates. Incomplete resection, even with radioactive implants in the residual tumor, yielded low survival rates. Surgical resection of pulmonary métastases from colo¬ rectal carcinoma resulted in notable survival statistics and should be offered to properly selected candidates.
Downloaded From: http://archsurg.jamanetwork.com/ by a New York University User on 06/05/2015
References 1. Divis C. Einbertrag zur Operativen, Behandlung der Lungengeschuuilste. Acta Chir Scand. 1927;62:329. 2. Barney JD, Churchill ET. Adenocarcinoma of the kidney with metastasis to the lung cured by nephrectomy and lobectomy. J Urol. 1939;42:269\x=req-\
276. 3. Brister SJ, DeVarennes B, Gordon PH, Sheiner NM, Pym J. Contemporary operative management of pulmonary metastasis of colorectal origin. Dis Colon Rectum. 1988;31:786-792. 4. Marcove RC, Huvos AG. Osteogenic sarcoma in childhood. N Y State J Med. 1971;71:857-859. 5. Martini N, Huvos AG, Mike V. Multiple pulmonary resections in the treatment of osteogenic sarcoma. Ann Thorac Surg. 1971;12:271-280. 6. McCormack PM, Martini N. The changing role of surgery for pulmonary metastases. Ann Thorac Surg. 1979;28:139-145. 7. Takita H, Edgerton F, Karakousis C. Surgical management of metastases to
lung. Surg Gynecol Obstet. 1981;152:791-794. August DA, Ottow RT, Sugarbaker PH. Clinical perspective of human
the
8.
colorectal cancer metastasis. Cancer Metastasis Rev. 1984;3:303-324. 9. Goya T, Miyasawa N, Kondo H, Tsuchiya R, Naruk ET, Svemoser K. Surgical resection of pulmonary metastasis from colorectal cancer. Cancer.
1989;64:1418-1421. 10. Mansel JK, Zinmeister AR, Pairolero PC, Jett JR. Pulmonary resection of metastatic colorectal adenocarcinoma, a 10-year experience. Chest. 1986;89:109-112. 11. Mayo CW, Schlicke CP. Carcinoma of the colon and rectum: a decade of experience at the Lahey Clinic. Dis Colon Rectum. 1978;22:717-720. 12. McCormack PM, Attiyeh FF. Resected pulmonary metastases from colorectal cancer. Dis Colon Rectum. 1979;22:553-556. 13. Johnson MR. Median sternotomy for resection of pulmonary metastasis. J Thorac Cardiovasc Surg. 1983;85:516. 14. Chang AE, Schaner EG, Conkle DM, Flye MW, Doppman JL, Rosenberg SA. Evaluation of computed tomography in the detection of pulmonary metastases: a prospective study. Cancer. 1979;43:913-916. 15. Sugarbaker PH, MacDonald JS, Gunderson LL. Colorectal cancer. In:
DeVita VT Jr, Hellman S, Rosenberg SA, eds. Principles and Practice of Oncology. Philadelphia, Pa: JB Lippincott Co; 1982:643-723. 16. Duncan W. Adjuvant radiation therapy. In: DeCosse JJ, ed. Large Bowel Cancer. Edinburgh, Scotland: Churchill Livingstone; 1981:166-175. 17. Kligerman MM. Preoperative radiation therapy in rectal cancer. Cancer.
1975;36:691-695.
18. Sischy B. The place of radiotherapy in the management of rectal adenocarcinoma. Cancer. 1982;50:2631-2637. 19. Giles GR, Leveson SH. Adjuvant chemotherapy and radiotherapy in colorectal cancer. In: Miles I, Beart RW, eds. Gastroenterological Surgery. London, England: Butterworths; 1983:172-197. 20. Higgins GA. Current status of adjuvant therapy in the treatment of large bowel cancer. Surg Clin North Am. 1983;63:137-150. 21. Dwight RW, Higgins GA, Keehn RJ. Factors influencing survival after resection in cancer of the colon and rectum. Am J Surg. 1979;117:512-522. 22. Dwight RW, Humphrey SW, Higgins GA. FUDR as an adjuvant to surgery in cancer of the large bowel. J Surg Oncol. 1973;5:243-249. 23. Higgins GA, Lee LE, Dwight RW. The case for adjuvant fluorouracil in colorectal cancer. Cancer Clin Trials. 1978;1:35-41. 24. Gastrointestinal Tumor Study Group. Adjuvant therapy of colon cancer: results of a prospectively randomized trial. N Engl J Med. 1984;310: 737-745. 25. Cahan WG, Castro EB, Hajdu SI. The significance of a solitary lung shadow in patients with colon carcinoma. Cancer. 1974;33:414-421. 26. Vincent RG, Choski LB, Takita H, Guttierez AC. Surgical resection of the solitary pulmonary metastasis. In: Weiss L, Gilbert HA, eds. Pulmonary Metastases. Boston, Mass: GK Hall; 1978:232-242. 27. Mountain CF, Khali KG, Hermes KE, Frazier DH. The contribution of surgery to the management of carcinomatous pulmonary metastases. Cancer.
1978;41:833-840.
28. Wilkins EW Jr. The status of pulmonary resection of metastases: experience at MGH. In: Weiss L, Gilbert HA, eds. Pulmonary Metastases. Boston, Mass: GK Hall; 1978:271-281. 29. Morrow CE, Vassilopoulos PP, Grage TB. Surgical resection of metastatic neoplams of the lung. Cancer. 1980;45:2981.
In Other AMA
Journals
ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE Tissue Calcification After An
Autopsy Study
Orthotopic
Mitchell S. Wachtel, MD; Urmila
Liver
Transplantation:
Khettry, MD;
Charles F. Arkin, MD
A retrospective review of 25 patients who underwent orthotopic liver transplanta¬ tion was performed to relate the prevalence and preferred sites of microscopic cal¬ cium deposition seen at autopsy to clinical parameters, namely, hypercalcemia, hyperphosphatemia, and renal failure. Microscopic foci of calcification were noted in 84% of patients, and hypercalcemia was noted in 68%. Multiple regression analysis demonstrated that the number of microscopically calcified organs depended in part on the peak total serum calcium level and the duration of hypercalcemia and that the peak total serum calcium level depended in part on the peak phosphorus level and the quantity of calcium administered intraoperatively. Univariate analysis showed that peak phosphorus level was partially dependent on the peak creatinine level. The data suggest that hypercalcemia and postoperative ectopic calcification are common and related occurrences following hepatic transplantation and that in¬ traoperative manipulations of serum calcium levels and renal failure partially, but not entirely, account for this phenomenon (Arch Pathol Lab Med. 1992;116:930-933).
Reprint requests to Department of Pathology, New England Deaconess Hospital, 185 Pilgrim Rd, Boston, MA 02215 (Dr Khettry).
Downloaded From: http://archsurg.jamanetwork.com/ by a New York University User on 06/05/2015
Metastases
10-Year Results Patricia M.
McCormack, MD; Michael E. Burt, MD, PhD; Manjit S. Bains, MD; Nael Martini, MD; Valerie W. Rusch, MD; Robert J. Ginsberg, MD
Background.\p=m-\Metastasectomyfor colorectal carcinoma lung is controversial. We analyzed results of this approach to justify its credibility. Methods.\p=m-\Westudied 144 patients by retrospective review after complete resection of lung metastases from colorectal cancer from 1965 through 1988. Patient selection and prognostic factors influencing survival were analyzed. Survival was analyzed by the Kaplan-Meier method, and comparisons were made by log-rank analysis. Results.\p=m-\Atotal of 170 thoracotomies were performed in 144 patients. The overall 5- and 10-year survival was 40% and 30%, respectively. Those patients undergoing complete resection of their metastases survived significantly longer than those undergoing incomplete resections. Conclusion.\p=m-\Itappears that resection of pulmonary metastases from colorectal carcinoma translates into long\x=req-\ \s=b\
to the
term survival benefit.
(Arch Surg. 1992;127:1403-1406) of the
first successful metastasectomy, by report Churchill2 The vis,1 appeared 1939, Barney first successful of recorded Di¬ and the case in an American journal a long-term survival after nephrectomy and pulmonary lobectomy for metastatic renal cell carcinoma. According to Blister et al,3 Blalock recorded the first resection of a colorectal metastasis to the lung in 1944. For the next two decades, progress was slow. Case selection was limited to patients in whom a lung lesion appeared well after the primary was removed, or to patients with only one lung lesion or, in rare cases, two le¬ sions situated in the same lung. The surgical approach to metastatic tumors to the lungs was justified by the improved survival statistics for sar¬ coma primary tumors.4"7 Application of this approach to primary carcinomas has followed more cautiously. The second most common cancer in the United States is colorectal carcinoma. Thirty percent of these patients in 1927. In
1992. From the Thoracic Service, Department of Surgery, Memorial Sloan\x=req-\ Kettering Cancer Center, New York, NY. Presented at the 45th Annual Cancer Symposium of the Society of Surgical Oncology, New York, NY, March 17, 1992. Reprint requests to Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021 (Dr McCormack).
Accepted for publication August 8,
present with advanced disease and
are incurable. Of the remainder who undergo curative colon resections, nearly half develop recurrent cancer.8 Twenty percent of recurrent cancers are located in the lungs, as well as other sites in the body.9,10 Yet, only 2% to 4% of patients with primary colorectal carcinoma have métastases only in the lungs after a curative resection.11,12 This select group of patients is targeted for this report.
PATIENTS AND METHODS At Memorial Sloan-Kettering Cancer Center, New York, NY a retrospective review was undertaken of the patients who under¬ went resection of pulmonary métastases from primary colorectal carcinomas between 1965 and 1988. The charts of 144 patients were analyzed; there were 55 women and 89 men. Ages ranged from 26 to 83 years. In a majority of the cases, the lesions appeared between the fifth and seventh decades of life, the incidence in the men peaking 10 years later than that in the women. Follow-up was possible in all but four patients. All four were free of disease 2 to 5 years after surgery. In 16 charts, the primary surgery had been performed else¬ where, and no data were available as to staging. Before pulmonary resection, the extent of disease was carefully evaluated to be certain there was no disease elsewhere in the body. The liver, in particular, was free of disease. All the patients fit the criteria established as prerequisites for lung resection for metastatic disease. There was no tumor elsewhere, no better therapy was available, and complete resection was possible. Pul¬ monary function tests, including diffusion capacity and arterial blood gases, were performed in all candidates. If test results showed that the pulmonary resection required to remove all dis¬ ease would still leave sufficient lung tissue for daily activities, this was judged to be adequate. In this study, survival time was calculated from the date of the pulmonary resection. Survival was calculated by the Kaplan-Meier method, and all comparisons were done by logrank analysis.
RESULTS Métastases were limited to one lung in 83% (120/144) of these patients. In 55% (80/144) of the patients, there was a single lesion. Of the 17% (24/144) with bilateral lesions, two patients had a single lesion in each lung, while the re¬ mainder had multiple bilateral métastases. One hundred seventy thoracotomies were performed in these 144 patients. Simultaneous bilateral metastasectomies were performed via sternotomies in 16 patients. The
Downloaded From: http://archsurg.jamanetwork.com/ by a New York University User on 06/05/2015
1001
loo
jet
80 80 "
Ht
60
.5
40
à
"^S /^X
40
>1
-
0
12
24
36
48
60
Time,
Fig 1.—Overall survival rate at 5 and
72
84
96
108
10 years (N=144).
lung.
Eleven patients could not have a complete resection be¬ of borderline pulmonary reserve. These patients had implantation of iodine 131 in the unresectable residual tu¬ mor. The median survival of these patients was nine months (range, 2 to 18 months), with all patients dying of progressive disease. There were no perioperative deaths, and three patients experienced morbidity (two patients had prolonged air leak and one had arrhythmia). Pathologic evaluation of the primary colorectal cancer showed Dukes stage C in 64 patients, Dukes stage B in 42 patients, and Dukes stage A in 17 patients. Four patients had squamous cell carcinoma of the rectum, one had cloacagenie tumor, and in 16 patients adenocarcinomas could not be staged because surgery had been done elsewhere and no data were available. The interval from resection of the primary tumor to re¬ section of the lung métastases is described as the diseasefree interval (DFI). Seventeen patients presented with pri¬ mary and metastatic disease simultaneously. Eighteen patients developed lung lesions within 1 year of treatment of the primary cancer. The remaining 109 patients devel¬ oped pulmonary métastases more than 1 year after resec¬ tion of the colorectal primary. The overall survival rate calculated by the Kaplan-Meier method was 44% at five years and 26% at 10 years (Fig 1). The prognostic indicators for survival analysis most of¬ ten mentioned in the literature are the number of resected nodules, the DFI, and the site or stage of the primary tu¬ mor. The majority of these patients (80/144) presented with a solitary lung lesion. One lesion in each lung was cause
in just two patients. Forty patients presented multiple lesions limited to one lung, while the remaining 22 patients had multiple bilateral lesions.
with
seen
12
24
36
Time,
Fig 2.—Number of nodules were not significant.
vs
72
60
48
mo
volume of lung removed was related to the location of the tumor. Complete resection was a prerequisite for good re¬ sults. Thirty-four lobectomies were required, where tumor location precluded a lesser resection. Wedge resection was the most common procedure (97/170). In instances where the patient had bilateral lesions, the approach was dictated by pulmonary reserve and location of lesions. Staged posterolateral thoracotomies during a single hospital stay allowed the best exposure to each lung for posterior lesions or lesions in the left lower lobe. Me¬ dian sternotomy was used more frequently when the lesions were few and anteriorly situated.13 A transverse sternotomy with bilateral anterior thoracotomies probably offers the best simultaneous approach to all aspects of each
rare,
0
120
(N=80)
~^~~~~~H-1-h
20
20
1 Nodule
i,
'
84
Nodule (N=64) 96
108
120
mo
survival at 5 and 10 years. Differences
100
Synchronous (N=1 7) Metachronous, 1 y (N=109)
80
12
24
36
48
60
Time,
72
84
96
108 120
mo
Fig 3.—Survival according to disease-free interval from primary colon resection to metastasectomy. Differences were not significant. Studies have shown that computed tomographic scan¬ nodules in the ning has the highest yield for lung parenchyma, being able to locate a 3-mm lesion. However, as proved by Chang et al,14 the accuracy in identifying malignant nodules is just 45%. An abnormal lesion seen on a chest roentgenogram has a 90% specific¬ ity, and a plane tomogram is 70% accurate for malignant neoplasms. Serial computed tomographic scans are now recommended as being both more specific and more sen¬ sitive in detecting significant pulmonary métastases.15 Figure 2 shows that there was no statistically significant difference in survival between patients with one or more than one completely resected pulmonary metastasis. Patients were divided into three groups according to DFI: those presenting with lung metastasis simultaneously with the primary colorectal tumor, those in whom the DFI was 12 months or less, and those whose DFI was more than 1 year. Figure 3 shows no survival advantage among these three groups. Analysis with respect to survival among the 123 tumors that could be staged is shown in Fig 4. There was neither a trend nor a difference among Dukes stages A, B, and C either at 5 or at 10 years. A combination of two indicators, namely, number of nodules and DFI, was compared by log-rank analysis. The comparison showed a trend for solitary lesions with a short DFI to have a better 5-year survival than multiple nodules
Downloaded From: http://archsurg.jamanetwork.com/ by a New York University User on 06/05/2015
identifying
lOOt-K 80 -
1^
Multiple, >1 y (N=45) Multiple, 1 y (N=64) Solitary, ^,
%^\
60
40
T
\ v~*1—v~-'A
mil
"
-1
iV
0
12
24
36
48
60
Time,
72
84
¡
B
XC
20-
96
108 120 48
mo
60
Time,
Fig 4.—Dûtes stages A (N=17), B (N=42), analysis. Differences were not significant.
108
72
120
mo
and C (N=64), and survival
Fig 5.—Number of nodules vs disease-free interval and survival pattern.
with a long DFI. At 10 years, this difference did not reach statistical significance (Fig 5).
Five-Year Survival After Resection of Métastases From Colorectal Primary Tumors
COMMENT Colorectal carcinoma remains the second most common visceral cancer in the nation in both incidence and deaths. Concerted efforts have been made with all treatment mo¬ dalities to improve the survival rate in these patients. Ra¬ diation therapy delivered preoperatively to postoperatively may decrease the incidence of local recurrence, and lead to somewhat longer survival.1619 Adjuvant chemo¬ therapy either as a single drug or in combination in randomized controlled trials has not, in general, offered any significant survival benefit.20"24 Patients with untreated state IV colorectal carcinoma live for 8 to 24 months. There is no significant 5-year sur¬ vival rate in treatment of the primary tumor or its recur¬ rences by any treatment modality other than surgery. Of all patients with curative resections, 10% to 20% will develop pulmonary métastases. Ten percent of these will have the lung as the sole metastatic site. Therefore, we an¬ alyzed a very select subsegment of all patients with colo¬ rectal carcinoma.8 The diagnosis is suspected initially most often when a chest roentgenogram is taken for another purpose, since these lesions produce no symptoms. Detection of a new solitary pulmonary nodule is not diagnostic of colorectal métastases. A benign lesion or a new lung primary lesion is a frequent occurrence, and diagnosis is essential.25 Computed tomographic scans clarify the status of the primary site and the presence or absence of intraabdominal recurrence or hepatic métastases. Colonoscopy verifies the condition of the anastomotic site. When there is no disease below the diaphragm, the respiratory func¬ tion of the patient is assessed. If the lung status will allow the required resection, this option for therapy should be offered to the patient. The operative procedure had no mortality and a very low morbidity in this study. This select group can achieve a 44% survival at 5 years and a 26% survival at 10 years, if the lung lesions are re¬ sected. Suitable candidates can be readily chosen from the group presenting with advanced lesions. A review of the literature9,12,2529 showed that this study compared favor¬ ably with other published series (Table). There is considerable variation to date regarding the use of prognostic variables in selecting candidates who are
Source, y Cahanetal,25 1974 Vincent et al,26 1978 Wilkins et al,28 1978 Mountain et al,29 1978 McCormackand Attiyeh,12 1979
al,29 1980 Goya et al,9 1989 »Rectal, 57%; colon, 0%. Morrow et
No. of Patients
% Survival
31
30
13
31*
34
28
28
28
35
22
16
13
65
41
most likely to benefit from this surgery. The analysis of the current data confirmed this finding. There are two contraindications to surgery: (1) insuffi¬ cient pulmonary reserve to accomplish a complete resec¬ tion; an incomplete resection results in a low rate of sur¬
vival; and (2) a "shower" of métastases, ie, a presentation of tiny nodules throughout the lung parenchyma, thus de¬ noting microscopic disease as well as macroscopic. In this
not possible. Such a presenta¬ usually be seen on a good-quality computed tomographic scan but will occasionally be a surprise find¬ ing at thoracotomy. Colorectal carcinoma métastases to the lung historically are usually few in number and have a relatively slow dou¬ bling time. This makes resection possible in the majority of
situation, total resection is tion
can
instances.262*
CONCLUSIONS of the data from 144 patients who had resection Analysis of pulmonary métastases from colorectal primary carci¬ noma showed a 44% survival rate at 5 years and 26% at 10 years. Neither the DFI, the number of nodules at presen¬ tation, nor the state of the primary colorectal cancer signif¬ icantly altered survival rates. Incomplete resection, even with radioactive implants in the residual tumor, yielded low survival rates. Surgical resection of pulmonary métastases from colo¬ rectal carcinoma resulted in notable survival statistics and should be offered to properly selected candidates.
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In Other AMA
Journals
ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE Tissue Calcification After An
Autopsy Study
Orthotopic
Mitchell S. Wachtel, MD; Urmila
Liver
Transplantation:
Khettry, MD;
Charles F. Arkin, MD
A retrospective review of 25 patients who underwent orthotopic liver transplanta¬ tion was performed to relate the prevalence and preferred sites of microscopic cal¬ cium deposition seen at autopsy to clinical parameters, namely, hypercalcemia, hyperphosphatemia, and renal failure. Microscopic foci of calcification were noted in 84% of patients, and hypercalcemia was noted in 68%. Multiple regression analysis demonstrated that the number of microscopically calcified organs depended in part on the peak total serum calcium level and the duration of hypercalcemia and that the peak total serum calcium level depended in part on the peak phosphorus level and the quantity of calcium administered intraoperatively. Univariate analysis showed that peak phosphorus level was partially dependent on the peak creatinine level. The data suggest that hypercalcemia and postoperative ectopic calcification are common and related occurrences following hepatic transplantation and that in¬ traoperative manipulations of serum calcium levels and renal failure partially, but not entirely, account for this phenomenon (Arch Pathol Lab Med. 1992;116:930-933).
Reprint requests to Department of Pathology, New England Deaconess Hospital, 185 Pilgrim Rd, Boston, MA 02215 (Dr Khettry).
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