Colorectal
Carcinoma
By R.A. Brown, H. Rode, A.J.W. Milk,
in Children
C. Sinclair-Smith,
and S. Cywes
Cape Town, South Africa l An increasing incidence of colorectal carcinoma has been noted at this institution. We report seven children with colorectal carcinoma. The average delay between onset of symptoms and diagnosis was 4% months, and in five patients distant metastases were present at the first operation. Initial symptoms were ignored in all cases and in only one was the serious nature of the condition realized at first presentation. In five lesions the histology was mucin secreting adenocarcinoma, a poor prognostic variant. All seven died on average 11 months after diagnosis. These three factors-delay in diagnosis, advanced stage of disease, and poorly differentiated histology-contribute overall to a poor prognosis in the young. Copyright o 1992 by W.B. Saunders Company INDEX WORDS: Colorectal carcinoma, pediatric.
P
RIMARY gastrointestinal tract malignancies constitute approximately 1% of paediatric neoplasms’ and, therefore, remain unsuspected in children, often presenting late with symptoms of intestinal obstruction. Less than 200 cases of carcinoma of the large bowel have been reported in children, but an increase has been noted in African-Americans, and four of the seven cases we report presented within the last 4 years. Unlike adult carcinoma of the large bowel, the overall prognosis is poor because of the delay in diagnosis, advanced stage of disease at presentation, and lack of histological differentiation. MATERIALS AND METHODS During the period 1962 to 1990. seven children aged 10 to 15 years (average, 12.3 years) have been seen with carcinoma of the
colon or rectum, with a sex ratio of 4M:3F. Three patients were black, three of mixed race. and one Caucasian. Their clinical data are detailed in Table 1. Overall duration of symptoms prior to presentation was 4.5 months (range, 2 to 6). Six of seven had poorly localised abdominal pain as their major complaint. Gastrointestinal tract disturbances were present in six, five with intermittent vomiting, one with diarrhoea, and only two having the classical signs of rectal bleeding and a palpable rectal mass. Appendicitis was the diagnosis entertained in four of the seven children (Table 1). Postappendicectomy symptoms of obstruction, complicated by a faecal hstula at the appendicectomy site in two, necessitated a second laparotomy to establish the correct diagnosis. Three patients were suspected of having other malignancies-Burkitt’s lymphoma, Ewing’s sarcoma with intraabdominal nodal spread, and nephroblastoma. Colon carcinoma was suspected ab initio in only one of these three, in whom an ultrasound of the kidney on the side of the suspected nephroblastoma showed a lesion involving the ascending colon, which was confirmed on barium enema as being carcinoma of the colon. The remaining two cases were diagnosed only at laparotomy with histological confirmation of the nodes or specimen. Anatomically, three lesions were situated in the ascending colon. one in the descending colon, one in the sigmoid colon. and two in the rectum. Distant metastases (Table 1) were identified in five of the seven patients. Despite the presence of metastases, the lesion could be resected with reestablishment of bowel continuity in all cases in which surgery was attempted. At surgery the lesions appeared inflamed, with attached omentum, palpable adjacent lymph nodes, and a nodular haemorrhagic appearance to the constricting lesion in the colon. Surgery was refused in one patient. There were no postoperative anastomotic complications. On histology all specimens showed adenocarcinoma, with mucin production in five (Fig 1). Four of these were poorly differentiated. with two having the “signet ring” subtype (Fig 2). Only one child had a well-differentiated adenocarcinoma. There were no survivors in this series. Average interval between diagnosis and death was 1I months (range, 4 to 25); all patients died of disseminated carcinomatosis. DISCUSSION Less than 1% of all malignant
growths of the large
bowel occur in persons under the age of 20,’ the youngest recorded case occurring in a 9-month-old girl2 It has been stated that the overall prognosis of large bowel carcinoma is independent of age,3,4 but
Fig 1. Poorly differentiated colloid sdenocarcinoms secreting abundant mucus (pale areas) and invading bowel wall. Ulceration of mucosa and submucosa (H&E, original magnification x 20).
h~f~~~off%di~Wic
SUrWrY, Vol 27, No 7 (July), 1992: pp gig-921
From the Departments of Paediatric Surgey and Pathology. Red Cross War Memorial Children’s Hospital and Institute of Child Health, University of Cape Town, Cape Town, South A,f?ica. Presented at the 38th Annual International Congress of the British Association of Paediatric Surgeons, Budapest. Hungary, Ju!v 24-26. 1991. Address reprint requests to R.A. Brown, MD. Department of Paediatric Surgery, Institute of Child Health, Red Cross Children’s Hospital, 7700 Rondebosch, South Africa. Copyright 10 1992 by W.B. Saunders Cornpuny 0022-346819212707-0033$03.OOlO
919
BROWN ET AL
920
Table 1. Characteristics Patient NO.
Age (Yr)
Durationof Symptoms(mo)
1
10
6
of Children With Colorectal Carcinoma Duke’s stage*
Initial Diagnosis
C
Cancer of rectum
Histology Adenocarcinoma,
mucin secreting,
poorly differentiated 2
12
5
D
Wilms’tumour
Adenocarcinoma,
moderately differ-
entiated 3
12
2
B
Appendicitis, appendicectomy
Adenocarcinoma,
mucin secreting,
signet ring, poorly differentiated 4
13
6
D
Appendicitis, ?worms
Adenocarcinoma,
mucin secreting,
well differentiated 5
15
“Months”
D
Appendicitis, appendicectomy
Adenocarcinoma,
moderately well
differentiated 6
11
3
D
Burkitt’s lymphoma
Adenocarcinoma,
mucin secreting,
signet ring, poorly differentiated 7
13
6
Appendicitis, appendicectomy. ing sarcoma)t
(Ew-
D
Adenocarcinoma,
mucin secreting,
poorly differentiated
*D, distant metastases. tSecond diagnosis.
our paediatric patients refute this contention as their prognosis was uniformly bad. This poor prognosis has also been reported by Goligher.5 There is a marked variation in racial incidence, six of the seven patients were non-Caucasians, and there have been reports from Zaire6 and Zambia’ as well as from three centres in South Africa*-lo corroborating this observation. In addition young African-Americans also seem more susceptible to developing carcinoma of the colon.ll This racial variation is repeated in other gastrointestinal tract lesions.‘* In our group there were no predisposing factors, although Enker et all3 report that up to 10% of preneoplastic disease such as ulcerative colitis and familial polyposis coli occur in patients under the age of 20. The poor prognosis of colorectal carcinoma in children may be attributed to three major factors: the site of the lesion, the delay in diagnosis with advanced
Fig 2. Adenocarcinoma colloid (C).
with signet ring subtype (+) and abundant
disease at presentation, and the predominant histological subtype. There is a higher incidence in children of involvement of the right and transverse colon (53%) compared with adults ( < 33%) and a far lower rate of involvement of the rectum (10% v 33%). Because of the more common midgut site of the tumour, pain is referred to the periumbilical and epigastric areas rather than the lower abdomen and rectal bleeding and a change in bowel habit are uncommon. In children there are many causes for pain arising in the midgut area that are far more common than carcinoma of the colon. Recurrent abdominal pain affects 10% to 15% of school-aged children,14 but organic pathology is found in less than 10% of these. In the present series, colonic carcinoma presented as a great imitator, with the preoperative diagnosis being made in only one patient with rectal bleeding and a palpable rectal mass, although intraabdominal lesions were suspected in three patients (Table 1). The remaining three had appendicectomies, complicated by postsurgical faecal fistulae in 2, before the correct diagnosis was established. Iron deficiency anaemia, a signal sign in adults, may not be as valuable in children, in whom it may be due to multifactorial causes, eg, poor nutrition, parasite infestation, and polyps. The occult blood test is a simple noninvasive procedure and if positive should arouse suspicion of bowel pathology requiring further investigation. Because the disease is unsuspected, presentation is usually at an advanced stage with up to 60% having luminal obstruction as opposed to the 18% in adults.5 At operation complete resection rate is markedly less than the 90% reported in adults; in the present series this was only possible in one of six patients, which is even less than the 40% figure reported in a childhood
COLORECTAL
CARCINOMA
921
IN CHILDREN
series from Rao et a1.15Resection, even palliative, is always preferable to short circuit because it effectively relieves the obstruction, and it reduces tumour bulk. Carcinoembryonic antigen estimation may be of use in recognising recurrence of tumour, with a postoperative drop followed by a gradual increase in titres as the recurrence enlarges. In five of the present cases the carcinoma was histologically typed as a mucin-producing adenocarcinoma, poorly differentiated in four (Fig 1). This is higher than the 50% incidence of mucin-producing carcinoma in young patients found by Middlekamp and Haffner.16 The prognosis associated with this histological subgroup is poor-there were no survivors in patients under 30 years old with mucin producing adenocarcinoma from Elliot and Louw’s series.q The mucin absorbs water, swells, and invades tissues, thereby promoting spread of malignant cells. It also interferes with the immune recognition of carcinoma cells due to mucopolysacharide coating.” The signet ring subtype has the worst prognosisi (Fig 2).
It is important to remember that although rare and often presenting in an apparently innocent unsuspicious manner, carcinoma of the colon does occur in children. Patients with recurrent abdominal pain, especially if prolonged, debilitating, or nocturnal, should have a careful abdominal palpation, a rectal examination, and a routine occult blood test particularly if there is associated weight loss and iron deficiency anaemia. The development of a faecal fistula postappendicectomy should alert the surgeon to the possibility of distal colonic obstruction from a carcinoma. Overall the very poor prognosis associated with carcinoma of the colon in children-less than 10% in a collected seriesI and all of the present patients dead within 25 months-will only improve with increased awareness leading to earlier diagnosis of this condition. ACKNOWLEDGMENT We would like to thank Dr C Lazarus of Cecelia Hospital, Ciskei, for allowing us to include his patients.
Makawane
REFERENCES I. Sessions RT, Riddell DH, Kaplan H.J. et al: Carcinoma of the colon in the lirst two decades of life. Ann Surg 162:279-2X4. 1965 2. Kern WH, White WC: Adenocarcinoma of the colon in a Y-month-old infant. Cancer 11:X55-857, 1958 3. Roth-Moyo LA. Devitt JE, Brown FN: The effect of age on the behaviour of carcinoma of the colon and rectum. Dis Col Rectum 11:420-422, 1968 4. Hardin WJ: Unusual manifestations of malignant disease of the large intestine. Surg Clin North Am 52:2X7-298. 1972 5. Goligher J: Surgery of the Anus. Rectum. and Colon (ed 5). London, England, Balliere Tindall, 19X5 6. Ngala Kenda JF: Cancer of the large bowel in the African: A 15 year survey at Kinshasha University Hospital, Zaire. Br J Surg 63:966-96X, 1976 7. Opiyo WJ, Din NA: Colorectal cancer under the age of twenty years. East Afr Med J 63:67-74, 1986 8. Pillay SP. Angorn IB, Baker LW: Colorectal carcinoma in young black patients-A report of eight cases. J Surg Oncol 10:125-132. 197X 9. Elliot MS, Louw JH: A IO year survey of large bowel carcinoma at Groote Schuur Hospital with particular reference to patients under 30 years of age. Br J Surg 66:621-624. 1979
10. Skalsky J. Jaques PH: Colorectal cancer in young blacks. An epidemic in Gazankulu? S Afr Med J 76:602-604. 1989 11. Chabalko JJ, Fraumeni JF: Colorectal cancer in children: Epidemiologic aspects. Dis Col Rectum 1X:1-3, 1075 12. Bradshaw E, Harington JS, McGlashan ND: Geographical distribution of lung and stomach cancers in South Africa 196X1972. S Afr Med J 64:655-663, 1984 13. Enker WE, Paloyan E, Kirsner JB: Carcinoma of the colon in the adolescent-A report of survival and an analysis of the literature. Am J Surg 133:737-741, 1977 14. Apley J, Naish N: Recurrent abdominal pains: A field survey of 1000 school children. Arch Dis Child 33:165-170. 195X 15. Rao BN. Pratt CB. Fleming ID. et al: Colon carcinoma in children and adolescents. A review of 30 cases. Cancer 55:13221326,19X5 16. Middlekamp JN, Haffner H: Carcinoma of the colon in children. Pediatrics 32:55X-571, 1963 17. Symmonds DA. Vickery AL: Mutinous carcinoma of the colon and rectum. Cancer 37:1X91-1900. I976 18. Halvorsen TB, Seim E: Influence of mutinous components on survival in colorectal adenocarcinomas: A multivariate analysis. J Clin Pathol41:1068-1072, 1988
Carcinoma
By R.A. Brown, H. Rode, A.J.W. Milk,
in Children
C. Sinclair-Smith,
and S. Cywes
Cape Town, South Africa l An increasing incidence of colorectal carcinoma has been noted at this institution. We report seven children with colorectal carcinoma. The average delay between onset of symptoms and diagnosis was 4% months, and in five patients distant metastases were present at the first operation. Initial symptoms were ignored in all cases and in only one was the serious nature of the condition realized at first presentation. In five lesions the histology was mucin secreting adenocarcinoma, a poor prognostic variant. All seven died on average 11 months after diagnosis. These three factors-delay in diagnosis, advanced stage of disease, and poorly differentiated histology-contribute overall to a poor prognosis in the young. Copyright o 1992 by W.B. Saunders Company INDEX WORDS: Colorectal carcinoma, pediatric.
P
RIMARY gastrointestinal tract malignancies constitute approximately 1% of paediatric neoplasms’ and, therefore, remain unsuspected in children, often presenting late with symptoms of intestinal obstruction. Less than 200 cases of carcinoma of the large bowel have been reported in children, but an increase has been noted in African-Americans, and four of the seven cases we report presented within the last 4 years. Unlike adult carcinoma of the large bowel, the overall prognosis is poor because of the delay in diagnosis, advanced stage of disease at presentation, and lack of histological differentiation. MATERIALS AND METHODS During the period 1962 to 1990. seven children aged 10 to 15 years (average, 12.3 years) have been seen with carcinoma of the
colon or rectum, with a sex ratio of 4M:3F. Three patients were black, three of mixed race. and one Caucasian. Their clinical data are detailed in Table 1. Overall duration of symptoms prior to presentation was 4.5 months (range, 2 to 6). Six of seven had poorly localised abdominal pain as their major complaint. Gastrointestinal tract disturbances were present in six, five with intermittent vomiting, one with diarrhoea, and only two having the classical signs of rectal bleeding and a palpable rectal mass. Appendicitis was the diagnosis entertained in four of the seven children (Table 1). Postappendicectomy symptoms of obstruction, complicated by a faecal hstula at the appendicectomy site in two, necessitated a second laparotomy to establish the correct diagnosis. Three patients were suspected of having other malignancies-Burkitt’s lymphoma, Ewing’s sarcoma with intraabdominal nodal spread, and nephroblastoma. Colon carcinoma was suspected ab initio in only one of these three, in whom an ultrasound of the kidney on the side of the suspected nephroblastoma showed a lesion involving the ascending colon, which was confirmed on barium enema as being carcinoma of the colon. The remaining two cases were diagnosed only at laparotomy with histological confirmation of the nodes or specimen. Anatomically, three lesions were situated in the ascending colon. one in the descending colon, one in the sigmoid colon. and two in the rectum. Distant metastases (Table 1) were identified in five of the seven patients. Despite the presence of metastases, the lesion could be resected with reestablishment of bowel continuity in all cases in which surgery was attempted. At surgery the lesions appeared inflamed, with attached omentum, palpable adjacent lymph nodes, and a nodular haemorrhagic appearance to the constricting lesion in the colon. Surgery was refused in one patient. There were no postoperative anastomotic complications. On histology all specimens showed adenocarcinoma, with mucin production in five (Fig 1). Four of these were poorly differentiated. with two having the “signet ring” subtype (Fig 2). Only one child had a well-differentiated adenocarcinoma. There were no survivors in this series. Average interval between diagnosis and death was 1I months (range, 4 to 25); all patients died of disseminated carcinomatosis. DISCUSSION Less than 1% of all malignant
growths of the large
bowel occur in persons under the age of 20,’ the youngest recorded case occurring in a 9-month-old girl2 It has been stated that the overall prognosis of large bowel carcinoma is independent of age,3,4 but
Fig 1. Poorly differentiated colloid sdenocarcinoms secreting abundant mucus (pale areas) and invading bowel wall. Ulceration of mucosa and submucosa (H&E, original magnification x 20).
h~f~~~off%di~Wic
SUrWrY, Vol 27, No 7 (July), 1992: pp gig-921
From the Departments of Paediatric Surgey and Pathology. Red Cross War Memorial Children’s Hospital and Institute of Child Health, University of Cape Town, Cape Town, South A,f?ica. Presented at the 38th Annual International Congress of the British Association of Paediatric Surgeons, Budapest. Hungary, Ju!v 24-26. 1991. Address reprint requests to R.A. Brown, MD. Department of Paediatric Surgery, Institute of Child Health, Red Cross Children’s Hospital, 7700 Rondebosch, South Africa. Copyright 10 1992 by W.B. Saunders Cornpuny 0022-346819212707-0033$03.OOlO
919
BROWN ET AL
920
Table 1. Characteristics Patient NO.
Age (Yr)
Durationof Symptoms(mo)
1
10
6
of Children With Colorectal Carcinoma Duke’s stage*
Initial Diagnosis
C
Cancer of rectum
Histology Adenocarcinoma,
mucin secreting,
poorly differentiated 2
12
5
D
Wilms’tumour
Adenocarcinoma,
moderately differ-
entiated 3
12
2
B
Appendicitis, appendicectomy
Adenocarcinoma,
mucin secreting,
signet ring, poorly differentiated 4
13
6
D
Appendicitis, ?worms
Adenocarcinoma,
mucin secreting,
well differentiated 5
15
“Months”
D
Appendicitis, appendicectomy
Adenocarcinoma,
moderately well
differentiated 6
11
3
D
Burkitt’s lymphoma
Adenocarcinoma,
mucin secreting,
signet ring, poorly differentiated 7
13
6
Appendicitis, appendicectomy. ing sarcoma)t
(Ew-
D
Adenocarcinoma,
mucin secreting,
poorly differentiated
*D, distant metastases. tSecond diagnosis.
our paediatric patients refute this contention as their prognosis was uniformly bad. This poor prognosis has also been reported by Goligher.5 There is a marked variation in racial incidence, six of the seven patients were non-Caucasians, and there have been reports from Zaire6 and Zambia’ as well as from three centres in South Africa*-lo corroborating this observation. In addition young African-Americans also seem more susceptible to developing carcinoma of the colon.ll This racial variation is repeated in other gastrointestinal tract lesions.‘* In our group there were no predisposing factors, although Enker et all3 report that up to 10% of preneoplastic disease such as ulcerative colitis and familial polyposis coli occur in patients under the age of 20. The poor prognosis of colorectal carcinoma in children may be attributed to three major factors: the site of the lesion, the delay in diagnosis with advanced
Fig 2. Adenocarcinoma colloid (C).
with signet ring subtype (+) and abundant
disease at presentation, and the predominant histological subtype. There is a higher incidence in children of involvement of the right and transverse colon (53%) compared with adults ( < 33%) and a far lower rate of involvement of the rectum (10% v 33%). Because of the more common midgut site of the tumour, pain is referred to the periumbilical and epigastric areas rather than the lower abdomen and rectal bleeding and a change in bowel habit are uncommon. In children there are many causes for pain arising in the midgut area that are far more common than carcinoma of the colon. Recurrent abdominal pain affects 10% to 15% of school-aged children,14 but organic pathology is found in less than 10% of these. In the present series, colonic carcinoma presented as a great imitator, with the preoperative diagnosis being made in only one patient with rectal bleeding and a palpable rectal mass, although intraabdominal lesions were suspected in three patients (Table 1). The remaining three had appendicectomies, complicated by postsurgical faecal fistulae in 2, before the correct diagnosis was established. Iron deficiency anaemia, a signal sign in adults, may not be as valuable in children, in whom it may be due to multifactorial causes, eg, poor nutrition, parasite infestation, and polyps. The occult blood test is a simple noninvasive procedure and if positive should arouse suspicion of bowel pathology requiring further investigation. Because the disease is unsuspected, presentation is usually at an advanced stage with up to 60% having luminal obstruction as opposed to the 18% in adults.5 At operation complete resection rate is markedly less than the 90% reported in adults; in the present series this was only possible in one of six patients, which is even less than the 40% figure reported in a childhood
COLORECTAL
CARCINOMA
921
IN CHILDREN
series from Rao et a1.15Resection, even palliative, is always preferable to short circuit because it effectively relieves the obstruction, and it reduces tumour bulk. Carcinoembryonic antigen estimation may be of use in recognising recurrence of tumour, with a postoperative drop followed by a gradual increase in titres as the recurrence enlarges. In five of the present cases the carcinoma was histologically typed as a mucin-producing adenocarcinoma, poorly differentiated in four (Fig 1). This is higher than the 50% incidence of mucin-producing carcinoma in young patients found by Middlekamp and Haffner.16 The prognosis associated with this histological subgroup is poor-there were no survivors in patients under 30 years old with mucin producing adenocarcinoma from Elliot and Louw’s series.q The mucin absorbs water, swells, and invades tissues, thereby promoting spread of malignant cells. It also interferes with the immune recognition of carcinoma cells due to mucopolysacharide coating.” The signet ring subtype has the worst prognosisi (Fig 2).
It is important to remember that although rare and often presenting in an apparently innocent unsuspicious manner, carcinoma of the colon does occur in children. Patients with recurrent abdominal pain, especially if prolonged, debilitating, or nocturnal, should have a careful abdominal palpation, a rectal examination, and a routine occult blood test particularly if there is associated weight loss and iron deficiency anaemia. The development of a faecal fistula postappendicectomy should alert the surgeon to the possibility of distal colonic obstruction from a carcinoma. Overall the very poor prognosis associated with carcinoma of the colon in children-less than 10% in a collected seriesI and all of the present patients dead within 25 months-will only improve with increased awareness leading to earlier diagnosis of this condition. ACKNOWLEDGMENT We would like to thank Dr C Lazarus of Cecelia Hospital, Ciskei, for allowing us to include his patients.
Makawane
REFERENCES I. Sessions RT, Riddell DH, Kaplan H.J. et al: Carcinoma of the colon in the lirst two decades of life. Ann Surg 162:279-2X4. 1965 2. Kern WH, White WC: Adenocarcinoma of the colon in a Y-month-old infant. Cancer 11:X55-857, 1958 3. Roth-Moyo LA. Devitt JE, Brown FN: The effect of age on the behaviour of carcinoma of the colon and rectum. Dis Col Rectum 11:420-422, 1968 4. Hardin WJ: Unusual manifestations of malignant disease of the large intestine. Surg Clin North Am 52:2X7-298. 1972 5. Goligher J: Surgery of the Anus. Rectum. and Colon (ed 5). London, England, Balliere Tindall, 19X5 6. Ngala Kenda JF: Cancer of the large bowel in the African: A 15 year survey at Kinshasha University Hospital, Zaire. Br J Surg 63:966-96X, 1976 7. Opiyo WJ, Din NA: Colorectal cancer under the age of twenty years. East Afr Med J 63:67-74, 1986 8. Pillay SP. Angorn IB, Baker LW: Colorectal carcinoma in young black patients-A report of eight cases. J Surg Oncol 10:125-132. 197X 9. Elliot MS, Louw JH: A IO year survey of large bowel carcinoma at Groote Schuur Hospital with particular reference to patients under 30 years of age. Br J Surg 66:621-624. 1979
10. Skalsky J. Jaques PH: Colorectal cancer in young blacks. An epidemic in Gazankulu? S Afr Med J 76:602-604. 1989 11. Chabalko JJ, Fraumeni JF: Colorectal cancer in children: Epidemiologic aspects. Dis Col Rectum 1X:1-3, 1075 12. Bradshaw E, Harington JS, McGlashan ND: Geographical distribution of lung and stomach cancers in South Africa 196X1972. S Afr Med J 64:655-663, 1984 13. Enker WE, Paloyan E, Kirsner JB: Carcinoma of the colon in the adolescent-A report of survival and an analysis of the literature. Am J Surg 133:737-741, 1977 14. Apley J, Naish N: Recurrent abdominal pains: A field survey of 1000 school children. Arch Dis Child 33:165-170. 195X 15. Rao BN. Pratt CB. Fleming ID. et al: Colon carcinoma in children and adolescents. A review of 30 cases. Cancer 55:13221326,19X5 16. Middlekamp JN, Haffner H: Carcinoma of the colon in children. Pediatrics 32:55X-571, 1963 17. Symmonds DA. Vickery AL: Mutinous carcinoma of the colon and rectum. Cancer 37:1X91-1900. I976 18. Halvorsen TB, Seim E: Influence of mutinous components on survival in colorectal adenocarcinomas: A multivariate analysis. J Clin Pathol41:1068-1072, 1988
