Melanoma Metastatic to Stomach, Small Bowel, or Colon Janet K. Ihde,
MD, FACS,
Daniel G. Coit,
Approximately 60% of patients who die from melanoma have gastrointestinal (Cl) metastases at autopsy, yet antemortem diagnosis is uncommon. A retrospective review was completed on 32 patients who underwent an operation at Memorial SloanKettering Cancer Center between 1977 and 1987 for complications of melanoma metastatic to the stomach, small bowel, or colon. Operations were most often performed on an emergent basis, and indications included bleeding or anemia in 12, ohstruction in 10, abdominal pain in 8, intestinal perforation in 1, and acute Cl bleeding with obstruction in 1. Cl involvement was the first sign of metastatic disease in 10 patients. Median survival after operation was 6.2 months (range: 1 to 42 months). Five patients were alive 2 years after operation, although only one remains free of disease 39 months after complete resection of a single site. Operative mortality was 3%, and 94% of patients were discharged from the hospital. Due to the low operative mortality, surgical palliation should he considered for those in whom the quality of life may he improved.
pproximately 60% of patients who die from melanoma have been noted at autopsy to have metastatic A disease involving the gastrointestinal (GI) tract; however, antemortem diagnosis is made in less than 5% of patients with melanoma [2,2]. Because patients who develop distant metastases from malignant melanoma have such a poor prognosis, surgical intervention is generally to be avoided. Occasional studies, however, have demonstrated prolonged survival in selected patients after resection of melanoma metastatic to the GI tract. In addition, other studies of symptomatic patients have demonstrated good palliation of symptoms with very low operative mortality and morbidity rates [3-a]. This review was undertaken to delineate the clinical presentation and the degree of palliation afforded by surgical management and to attempt to define factors predictive of survival in patients with GI metastases. From the Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York. Requests for reprints should be addressed to Daniel G. Coit, MD, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10021. Manuscript submitted April 2,1990, and accepted in revised form June 12,199O.
208
THE AMERICAN
JOURNAL OF SURGERY
MD, FACS,NWYO~~,NCW
PATIENTS
York
AND METHODS
A retrospective review defined 32 patients who re quired abdominal exploration for melanoma metastatic to the stomach, small bowel, or colon at the Memorial Sloan-Kettering Cancer Center between 1977 and 1987. Operations were most often emergent, and indications included bleeding or anemia in 12 (38%), GI obstruction in 10 (3 I%), abdominal pain in 8 (25%), bowel perforation in 1 (3%), and acute GI bleeding with obstruction in 1 (3%). This retrospective analysis examined characteristics of the primary tumor, including site and thickness, treatment of the primary and regional nodes, and the extent of systemic metastasis prior to onset of GI symp toms. The presenting GI complaints that led to operative exploration, as well as operative findings and procedure, postoperative treatment, and eventual outcome, were also analyzed. RESULTS
Of the 32 patients who underwent operative exploration for metastatic melanoma to the GI tract, 20 were men and 12 were women. The median age of the patients was 45 years (range: 26 to 68 years). The primary melanoma site was truncal in 13 patients (41%), upper or lower extremity in 7 patients (22%), and head and neck in 5 patients (15%). An “occult” primary was never found in seven patients (22%). Most of the patients in whom the Clark level or Breslow thickness of their tumor was recorded had disease that was less than 4 mm and at or less than Clark level IV (Table I). Six patients had only single site involvement, while the remaining 26 had multiple site involvement. Sites of me tastases were the stomach in 2 patients, the duodenum in 5 patients, the jejunum in 13 patients, the ileum in 18 patients, and the colon in 5 patients. In 12 patients, contiguous tumor was noted in the small bowel mesentery, which necessitated small bowel resection. The typical operative and gross appearance of melanoma metastatic to the mid-jejunum is shown in Figure 1. Of 24 patients who had undergone prior regional node dissections, 16 had histologically positive nodes, repro senting half of the study population. Of the 24 prior regional node dissections, 12 were elective, 8 with negative nodes and 4 with positive nodes. Twelve prior node dissections were therapeutic, all involving positive nodes. GI involvement as the first manifestation of metastatic disease occurred in 10 patients (31%); it was the first and only manifestation of metastatic disease in 7 patients and was the first site synchronous with other systemic disease in 3 patients. Two patients presented with melanoma metastatic to the GI tract without a known prior diagnosis of melanoma. In the remaining patients, the
VOLUME 162 SEPTEMBER 1991
most common site of prior systemic involvement included soft tissue in 12 (38%) followed by lung in 7 patients (22%), brain in 3 (9%), and bone in 3 (9%); most patients had multiple areas of metastatic involvement. Only six patients (19%) had liver involvement at the time of exploration. Additional treatment in the 25 patients with a history of a primary melanoma included chemotherapy in 10 patients and/or immunotherapy in 9 patients; 12 of 25 patients had received no chemotherapy or immunotherapy prior to the development of GI metastasis. In the 25 patients with a known primary melanoma, the median time from diagnosis to the first systemic metastasis was 26 months (range: 3 to 252 months). Eight of 25 patients (32%) with known primary melanomas developed their first systemic metastasis more than 5 years after treatment of their primary tumor. In 12 of those 25 patients (48%), metastatic disease to the GI tract presented more than 5 years after initial treatment of the primary tumor. The median time from development of extra-GI metastatic dii to the subsequent development of GI metastasis was 12 months (range: 2 to 48 months). At operation, 26 patients (81%) had multiple site involvement and only 4 of these patients had all gross tumor resected. Five patients had single site involvement of the GI tract, four of whom underwent complete resection of all visible tumor. Two patients with multiple site involvement and one patient with single site involvement of the pancreas and duodenum did not undergo any resection of disease. Of the eight patients undergoing complete resection of all GI metastases, five had small bowel resection, one had a small bowel resection with en bloc wedge gastrectomy, one had resection of small bowel mesentery, splenectomy, and bilateral salpingo-oophorectomy, and one had a partial colectomy. Of 21 patients undergoing partial resee tion, 17 had at least a segment of small bowel resected, 2 of these required simultaneous colon resection, 2 required simultaneous small bowel bypasses, and 1 required simultaneous wedge gastrectomy. Two patients in the partial resection group underwent pancreaticoduodenectomy for bleeding duodenal metastases.
TABLE I Level and Thickness of Primary Melanoma in Patlents Wlth Gastrointestinal Metastasis
Clark level II, Ill IV, v Unknown Breslow thickness 4.0 mm Unknown mm = millimeters
No. of Patients
%
11 0 13
34 25 41
0 6 1 6 3 16
0 19 3 19 9 50
depth.
Follow-up was available for all patients. The median survival for all patients was 6.2 months (range: 1 to 42 months), and the estimated overall survival was 18% at 3 years (Figure 2). Five patients survived 2 years with only one of these apparently d&ease-free at 39 months after complete resection of a single site of small bowel involvement. Median survival for eight patients undergoing complete resection of all disease was 10 months, compared with 5.3 months for patients undergoing less than complete resection (J?igure 3). Median survival for six patients with single site GI metastases was 14 months, compared with 5.1 months for patients with multiple site involvement (Figure 4). The trends toward improved survival in patients after complete resection or with only single site involvement were not statistically significant when analyzed by the logrank method, largely because of the small numbers of patients in these favorable sub groups. Of the patients with the most favorable prognosis, four with single site disease are undergoing complete resection, one patient has no evidence of disease at 39 months, one patient is alive with disease at 42 months,
THE AMERICAN JOURNAL OF SURGERY
VOLUME 162 SEPTEMBER 1991
209
IHDE AND COIT
, Proportion
TABLE II Operatlve Mortallty and Survlval After Gastrolntestlnal Surgery for Metastatlc Melanoma
Surviving
II 0.9 0.8 0.7 -
Reference
0.6 0.5 0.4 o.3-;::
No. of Patients
No. of Patients Median Operative Mortality (%) Survival (mo) Alive at 2 Years
131 WI (61
16 15 33*
16 0 0
4.5 6.0 0.5
2 2 -
121
23 32
9 3
7.5 6.2
3 4
Current series
*Smallbowelonly.
24
Time (Months)
Figure 2. Overall suvlval after surgical resection of melanoma metastatlc to stomach, small bowel, or colon.
of the primary to onset of GI metastasis was greater than versus less than the median of 2 years. Despite poor long-term survival, the operative mortality, defined as death within 30 days of operation, was only 3%, and 94% of patients were discharged from the hospital. COMMENTS
and two others have died of disease at 14 and 19 months, respectively, after resection. There was no difference in survival when comparing patients with a known versus unknown primary site, or when comparing patients whose interval from diagnosis
It is apparent from this review that GI and other metastases can occur several years after apparently successful treatment of a primary melanoma. The longest time interval in this series was 21 years after apparently successful resection of an “early” tumor of the ear. As noted above, the depth and the stage of the primary melanoma tumor did not correlate well with the risk of development of systemic disease; patients with early tumors as well as those without regional lymph node involvement developed disseminated disease. Vague abdominal complaints, often attributed to unrelated causes such as concurrent adjuvant therapy, may represent GI involvement with metastatic disease despite a long time interval [ 71. Reported presenting signs and symptoms include acute or more often chronic GI bleeding [a, dysphagia, vomiting or abdominal pain from obstruction and intussusception [6,8], and weight loss, malabsorption, or diarrhea [1,9]. This spectrum was reflected in our series. The stomach, small bowel, or colon may be the only clinically evident site of metastasis from melanoma, as seen in seven of the patients in this series, two of whom had no prior diagnosis of melanoma. Three other patients presented with metastatic melanoma to the GI tract in association with synchronous systemic metastases without a prior diagnosis of melanoma. Thus, 10 of 32 patients (31%) presented with GI metastases as their first sign of systemic melanoma. This is comparable to prior reports by Klaase and Kroon [2] (4 of 23 patients or 17%) and Jorge et al [ZO] (5 of 15 patients or 33%). For the majority of patients, the diagnosis of melanoma metastatic to the GI tract continues to carry a poor prognosis. Other series have reported median survivals ranging from 4 to 9 months (Table II). While one would expect that complete resection of all tumor should result in the best overall survival [5], this was reflected in an improved median but not overall survival distribution in our review. Similar results were noted when comparing
210
162
24
36
48
Time (Months)
Flgure 3. Suvival by resectabIlIty in patients with melanoma metashtk to st0tnad-1,small bowel, w colon. Compk3terese5 tion = CR. Less then Completereseotlon =
MD, FACS,
Daniel G. Coit,
Approximately 60% of patients who die from melanoma have gastrointestinal (Cl) metastases at autopsy, yet antemortem diagnosis is uncommon. A retrospective review was completed on 32 patients who underwent an operation at Memorial SloanKettering Cancer Center between 1977 and 1987 for complications of melanoma metastatic to the stomach, small bowel, or colon. Operations were most often performed on an emergent basis, and indications included bleeding or anemia in 12, ohstruction in 10, abdominal pain in 8, intestinal perforation in 1, and acute Cl bleeding with obstruction in 1. Cl involvement was the first sign of metastatic disease in 10 patients. Median survival after operation was 6.2 months (range: 1 to 42 months). Five patients were alive 2 years after operation, although only one remains free of disease 39 months after complete resection of a single site. Operative mortality was 3%, and 94% of patients were discharged from the hospital. Due to the low operative mortality, surgical palliation should he considered for those in whom the quality of life may he improved.
pproximately 60% of patients who die from melanoma have been noted at autopsy to have metastatic A disease involving the gastrointestinal (GI) tract; however, antemortem diagnosis is made in less than 5% of patients with melanoma [2,2]. Because patients who develop distant metastases from malignant melanoma have such a poor prognosis, surgical intervention is generally to be avoided. Occasional studies, however, have demonstrated prolonged survival in selected patients after resection of melanoma metastatic to the GI tract. In addition, other studies of symptomatic patients have demonstrated good palliation of symptoms with very low operative mortality and morbidity rates [3-a]. This review was undertaken to delineate the clinical presentation and the degree of palliation afforded by surgical management and to attempt to define factors predictive of survival in patients with GI metastases. From the Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York. Requests for reprints should be addressed to Daniel G. Coit, MD, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10021. Manuscript submitted April 2,1990, and accepted in revised form June 12,199O.
208
THE AMERICAN
JOURNAL OF SURGERY
MD, FACS,NWYO~~,NCW
PATIENTS
York
AND METHODS
A retrospective review defined 32 patients who re quired abdominal exploration for melanoma metastatic to the stomach, small bowel, or colon at the Memorial Sloan-Kettering Cancer Center between 1977 and 1987. Operations were most often emergent, and indications included bleeding or anemia in 12 (38%), GI obstruction in 10 (3 I%), abdominal pain in 8 (25%), bowel perforation in 1 (3%), and acute GI bleeding with obstruction in 1 (3%). This retrospective analysis examined characteristics of the primary tumor, including site and thickness, treatment of the primary and regional nodes, and the extent of systemic metastasis prior to onset of GI symp toms. The presenting GI complaints that led to operative exploration, as well as operative findings and procedure, postoperative treatment, and eventual outcome, were also analyzed. RESULTS
Of the 32 patients who underwent operative exploration for metastatic melanoma to the GI tract, 20 were men and 12 were women. The median age of the patients was 45 years (range: 26 to 68 years). The primary melanoma site was truncal in 13 patients (41%), upper or lower extremity in 7 patients (22%), and head and neck in 5 patients (15%). An “occult” primary was never found in seven patients (22%). Most of the patients in whom the Clark level or Breslow thickness of their tumor was recorded had disease that was less than 4 mm and at or less than Clark level IV (Table I). Six patients had only single site involvement, while the remaining 26 had multiple site involvement. Sites of me tastases were the stomach in 2 patients, the duodenum in 5 patients, the jejunum in 13 patients, the ileum in 18 patients, and the colon in 5 patients. In 12 patients, contiguous tumor was noted in the small bowel mesentery, which necessitated small bowel resection. The typical operative and gross appearance of melanoma metastatic to the mid-jejunum is shown in Figure 1. Of 24 patients who had undergone prior regional node dissections, 16 had histologically positive nodes, repro senting half of the study population. Of the 24 prior regional node dissections, 12 were elective, 8 with negative nodes and 4 with positive nodes. Twelve prior node dissections were therapeutic, all involving positive nodes. GI involvement as the first manifestation of metastatic disease occurred in 10 patients (31%); it was the first and only manifestation of metastatic disease in 7 patients and was the first site synchronous with other systemic disease in 3 patients. Two patients presented with melanoma metastatic to the GI tract without a known prior diagnosis of melanoma. In the remaining patients, the
VOLUME 162 SEPTEMBER 1991
most common site of prior systemic involvement included soft tissue in 12 (38%) followed by lung in 7 patients (22%), brain in 3 (9%), and bone in 3 (9%); most patients had multiple areas of metastatic involvement. Only six patients (19%) had liver involvement at the time of exploration. Additional treatment in the 25 patients with a history of a primary melanoma included chemotherapy in 10 patients and/or immunotherapy in 9 patients; 12 of 25 patients had received no chemotherapy or immunotherapy prior to the development of GI metastasis. In the 25 patients with a known primary melanoma, the median time from diagnosis to the first systemic metastasis was 26 months (range: 3 to 252 months). Eight of 25 patients (32%) with known primary melanomas developed their first systemic metastasis more than 5 years after treatment of their primary tumor. In 12 of those 25 patients (48%), metastatic disease to the GI tract presented more than 5 years after initial treatment of the primary tumor. The median time from development of extra-GI metastatic dii to the subsequent development of GI metastasis was 12 months (range: 2 to 48 months). At operation, 26 patients (81%) had multiple site involvement and only 4 of these patients had all gross tumor resected. Five patients had single site involvement of the GI tract, four of whom underwent complete resection of all visible tumor. Two patients with multiple site involvement and one patient with single site involvement of the pancreas and duodenum did not undergo any resection of disease. Of the eight patients undergoing complete resection of all GI metastases, five had small bowel resection, one had a small bowel resection with en bloc wedge gastrectomy, one had resection of small bowel mesentery, splenectomy, and bilateral salpingo-oophorectomy, and one had a partial colectomy. Of 21 patients undergoing partial resee tion, 17 had at least a segment of small bowel resected, 2 of these required simultaneous colon resection, 2 required simultaneous small bowel bypasses, and 1 required simultaneous wedge gastrectomy. Two patients in the partial resection group underwent pancreaticoduodenectomy for bleeding duodenal metastases.
TABLE I Level and Thickness of Primary Melanoma in Patlents Wlth Gastrointestinal Metastasis
Clark level II, Ill IV, v Unknown Breslow thickness 4.0 mm Unknown mm = millimeters
No. of Patients
%
11 0 13
34 25 41
0 6 1 6 3 16
0 19 3 19 9 50
depth.
Follow-up was available for all patients. The median survival for all patients was 6.2 months (range: 1 to 42 months), and the estimated overall survival was 18% at 3 years (Figure 2). Five patients survived 2 years with only one of these apparently d&ease-free at 39 months after complete resection of a single site of small bowel involvement. Median survival for eight patients undergoing complete resection of all disease was 10 months, compared with 5.3 months for patients undergoing less than complete resection (J?igure 3). Median survival for six patients with single site GI metastases was 14 months, compared with 5.1 months for patients with multiple site involvement (Figure 4). The trends toward improved survival in patients after complete resection or with only single site involvement were not statistically significant when analyzed by the logrank method, largely because of the small numbers of patients in these favorable sub groups. Of the patients with the most favorable prognosis, four with single site disease are undergoing complete resection, one patient has no evidence of disease at 39 months, one patient is alive with disease at 42 months,
THE AMERICAN JOURNAL OF SURGERY
VOLUME 162 SEPTEMBER 1991
209
IHDE AND COIT
, Proportion
TABLE II Operatlve Mortallty and Survlval After Gastrolntestlnal Surgery for Metastatlc Melanoma
Surviving
II 0.9 0.8 0.7 -
Reference
0.6 0.5 0.4 o.3-;::
No. of Patients
No. of Patients Median Operative Mortality (%) Survival (mo) Alive at 2 Years
131 WI (61
16 15 33*
16 0 0
4.5 6.0 0.5
2 2 -
121
23 32
9 3
7.5 6.2
3 4
Current series
*Smallbowelonly.
24
Time (Months)
Figure 2. Overall suvlval after surgical resection of melanoma metastatlc to stomach, small bowel, or colon.
of the primary to onset of GI metastasis was greater than versus less than the median of 2 years. Despite poor long-term survival, the operative mortality, defined as death within 30 days of operation, was only 3%, and 94% of patients were discharged from the hospital. COMMENTS
and two others have died of disease at 14 and 19 months, respectively, after resection. There was no difference in survival when comparing patients with a known versus unknown primary site, or when comparing patients whose interval from diagnosis
It is apparent from this review that GI and other metastases can occur several years after apparently successful treatment of a primary melanoma. The longest time interval in this series was 21 years after apparently successful resection of an “early” tumor of the ear. As noted above, the depth and the stage of the primary melanoma tumor did not correlate well with the risk of development of systemic disease; patients with early tumors as well as those without regional lymph node involvement developed disseminated disease. Vague abdominal complaints, often attributed to unrelated causes such as concurrent adjuvant therapy, may represent GI involvement with metastatic disease despite a long time interval [ 71. Reported presenting signs and symptoms include acute or more often chronic GI bleeding [a, dysphagia, vomiting or abdominal pain from obstruction and intussusception [6,8], and weight loss, malabsorption, or diarrhea [1,9]. This spectrum was reflected in our series. The stomach, small bowel, or colon may be the only clinically evident site of metastasis from melanoma, as seen in seven of the patients in this series, two of whom had no prior diagnosis of melanoma. Three other patients presented with metastatic melanoma to the GI tract in association with synchronous systemic metastases without a prior diagnosis of melanoma. Thus, 10 of 32 patients (31%) presented with GI metastases as their first sign of systemic melanoma. This is comparable to prior reports by Klaase and Kroon [2] (4 of 23 patients or 17%) and Jorge et al [ZO] (5 of 15 patients or 33%). For the majority of patients, the diagnosis of melanoma metastatic to the GI tract continues to carry a poor prognosis. Other series have reported median survivals ranging from 4 to 9 months (Table II). While one would expect that complete resection of all tumor should result in the best overall survival [5], this was reflected in an improved median but not overall survival distribution in our review. Similar results were noted when comparing
210
162
24
36
48
Time (Months)
Flgure 3. Suvival by resectabIlIty in patients with melanoma metashtk to st0tnad-1,small bowel, w colon. Compk3terese5 tion = CR. Less then Completereseotlon =
