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Pneumatosis coli in adult acute myeloid leukaemia
Uin.RadioL (1979) 30, 175-178
Fneumatosis Coli in Adult Acute Myeloid Leukaemia I), McCARTHY, I. H O L L A N D , J. P. L A V E N D E R and D. C A T O V S K Y
From the Departments of Haematology and Diagnostic Radiology and the MRC Leukaemia Unit, Royal postgraduate Medical School and Harnrnersmith Hospital, London Three cases of pneumatosis coli (PC) in adult patients w i t h acute m y e l o i d leukaemia seen over the last five years in Hammersmith Hospital are reported. A l t h o u g h definite conclusions are impossible, we suggest t h a t that pneumatosis could be due to damage to t h e b o w e l m u c o s a as a result o f the disease or the treatment. ]'he literature is reviewed and discussed in an inconclusive a t t e m p t to discover the source o f the gas.
PC is a condition where gas is present in the colonic wall and is an u n c o m m o n finding in general radiological practice. Various patterns o f intramural gas have been reported, of which PC represents one_ Colquhoun (1965) presents a useful classification into three groups - namely, cystic pneumatosis, 'interstitial e m p h y s e m a ' and cases resulting f r o m infection. PC seems to represent cystic pneumatosis confined to the colon. Many causes for PC have b e e n postulated. It is suggested, in patients with respiratory disease, t h a t respiratory obstruction produces alveolar rupture and pulmonary interstitial e m p h y s e m a . The gas t h e n tracks to the lung hilum, the m e d i a s t i n u m and the retroperitoneal space, gaining access to the colnic wall by tracking along the b l o o d vessels f r o m t h e retroperitoneal space (Keyting et al., 1961). The association with obstructive b o w e l lesions is p o o r l y u n d e r s t o o d but is presumed to be on the basis o f raised intraluminal pressure forcing gas through the bowel wall (Colquhoun, 1965). Recently there have been reports of PC w i t h collagen disorders (Mueller et al., 1972) and malignant l y m p h o m a (O'Connell and T h o m p s o n , 1978). In acute c h i l d h o o d leukaemias six patients were described (Jaffe et al., 1972). F o u r of these patients had an ulcerated or infiltrated GIT suggesting these defects as the portal of gas entry. We have been unable to find any r e p o r t e d w i t h adult acute m y e l o i d leukaemia (AML) and accordingly present the following three cases.
CASE REPORTS Case 1. A.M. a 51-year-old Caucasian woman, developed AML in October 1973. Although previously asthmatic she had been well and was receiving no medication for the previous 18 years. Physical examination, and radiological evaluation of chest and abdomen showed no abnormality. Iliac crest bone marrow aspirate- was hypercellular with 90% myeloblasts. Chemotherapy was instituted via a subclavian line and consisted of six courses of daunorubicin and
cytosine arabinoside. An oral antibiotic regime (FRACON) with framycycetin, colistin, nystatin tablets and elixir was also commenced to sterilise the gut. Initially during treatment the patient had an episode of air embolism due to the disconnection of the subclavian line, and also developed diarrhoea but with no blood or mucus passed per rectum. Aerobic and anaerobic stool culture showed only a light growth of lactobacilli. A month following the start of treatment she developed prolapsed haemorrhoids, anal spasm and abdominal distension. The latter continued and a plain film of the abdomen showed a large quantity of retroperitoneal and intraperitoneal gas. As she was not in remission further chemotherapy was given but with no effect and she developed pytexia, further abdominal distension with peritonism, and died. At autopsy extensive candidiasis was found involving the myocardium, lungs, liver, spleen, kidneys and the oesophageal mucosa but with sparing of the remaining GI tract. Ulceration at the gastro-oesophageal junction was noted. There were gas 'bubbles' revolving all layers of the gut wall and paracolic tissue, from the caecum to the splenic flexure. No perforation was found. Case 2. D.W., a 24-year-old Caucasian woman, developed AML in February 1972. There was no past history of illness. Chemotherapy with daunorubicin, and other cytotoxic agents achieved a complete remission and also achieved further remissions following relapses in March 1974 and December 1975. In February 1977 maintenance chemotherapy was discontinued. Following a relapse in December 1977, physical examination and chest radiography showed no abnormality. Her marrow contained 60% blast forms. FRACON was administered (as for Case 1). Chemotherapy via a subclavian line was commenced. Following insertion of the subclavian line a small right apical pneumothorax was seen on a chest radiograph_ Further treatment achieved therapeutic aphasia. During treatment the patient was nauseous and had diarrhoea and vomiting. Following treatment she developed a mild respiratory infection with a normal chest X-ray. Antibiotics were prescribed and when the respiratory tract infection was resolving she developed abdominal distension with excess flatus and diarrhoea. Surgical emphysema was noted at this time in her right supraclavicular fossa. This was confirmed on a chest X-ray which also showed gas under both hemidiaphragms (Fig. 1). No pneumothorax or mediastinal gas was seen. Abdominal films with decubitus views (obtained with portable apparatus as the patient was isolated due to neutropenia) showed both intraand retroperitoneal gas. Linear gas translucencies were also seen outlining the walls of the ascending and transverse colons (Fig. 2). A diagnosis of pneumatosis coli was made.
176
CLINICAL RADIOLOGY
Fig. 1 - Case 2- Chest with CVP line in situ and gas under b o t h hemidiaphragms,
Fig. 2 - Case 2. A b d o m e n with retroperitoneal gas and subserosal gas outlining the proximal colon.
Fig. 3 - Case 3. Upper a b d o m e n with retro- and intraperitoneal air_ Note linear subserosal gas in descending colon.
PNEUMATOSIS COLI As the patient's abdominal symptoms subsided, t h e radiological appearances resolved. No specific treatment was given. The condition did n o t recur with subsequent chemotheraPY" Case 3. S.G.M., an 18-year-old Caucasian man, presented ~vith AML in February 1977. Previously well, on examination he was noted to be pale with splenomegaly and fundal haemorrhages. An iliac crest marrow aspirate was hypercellular with 85% blast cells. A chest X-ray at this time was normal. Chemotherapy was commenced with cyclophoshamide, vincristine, and other cytotoxic agents, along with RACON- Following this he became pyrexial and was treated with intravenous antibiotics. A second course o f chemotheraPY 10 days later failed to induce a remission. Aphthous ulceration was noted at this time. It was then decided to administer further chemotherapy via a subclavian line. A minor air embolism occurred during insertion of the line. Following chemotherapy the patient developed diarrhoea with abdominal distension and excessive flatus. Stool culture grow E. coil However, a chest radiograph showed gas under both hemidiaphragms, and abdominal radiographs showed a large quantity o f retroperitoneal gas. Linear gas translucencies were seen outlining the caecum, ascending, transverse and upper descending colon (Fig. 3). Small gas-filled cysts were also noted within the colonic wall. A diagnosis o f PC was made. A gastrografin meal showed a normal upper gastrointestinal tract. The symptoms and the radiotogical findings subsequently resolved over the following month and no recurrence occurred with subsequent chemotherapy- In April 1978, while in remission, the patient developed hepatitis B-antigen positive hepatitis, hepatic coma and died. Autopsy was not performed.
DISCUSSION Many causes for PC have been enumerated, but the occurrence of minor structural bowel abnormalities resulting from either the disease or the treatment ia cases of leukaemia is, in our opinion, most likely to account for the development o f the pneumatosis coll.
It can be seen that when PC occurred all three cases had AML; were aplastic as a result of treatment; were receiving gut sterilising antibiotics; had diarrhoea, abdominal distension and intraperitoneal gas. Air embolism occurred in Cases 1 and 3 and pneumothorax in Case 2. Case 1 was diagnosed at post-mortem examination and Cases 2 and 3 were recognised because of classical X-ray features. Case 1 differed from the other two patients in that she had disseminated candidiasis at autopsy. Candidal ulceration was found in the oesophagus, but there was no evidence of candidal infection lower in the intestinal tract. The candidal ulcer in the oesophagus is an unlikely site for gas entry as no cysts were present in the stomach at autopsy and there was no evidence of oesophageal perforation. I.eukaemic infiltration of the intestinal mucosa with .Consequent damage to its integrity is also possible tn this patient but was not demonstrated at autopsy. As the three patients were aplastic when the PC
177
developed, it may be that leukaemic bowel involvement had been present and resolved with chemotherapy. However, rio bowel symptoms were present in any patient at initial presentation. Infection with gas-forming bacteria resistant to the gut sterilisation regime must be mentioned as a possibility. However, only light growths of E. coli and lactobacilli occurred in stool cultures. The large amount of gas seen in the retroperitoneal space (Figs 1, 2) - separating diaphragm from liver if due to bacteria, could only be explained by massive gasforming infection, or by rupture o f a cyst or cysts, resulting in intestin~d perforation. Although Case 1 exhibited peritonism, no evidence of perforation was found and no peritonism was present in the other patients. Also file theoretical background supporting an infective cause is not strong, and is based on the isolation of a gas-forming E. coli from pigs with cystic pneumatosis and the failure to isolate it from normal pigs (Naeslund, 1924). We must also consider that all patients had air introduced as a result of insertion of subclavian intravenous lines, but it is difficult to conceive how air in the blood stream could be responsible for the condition. Pneumothorax could certainly be responsible for formation of cysts, as air has been demonstrated to migrate retroperitoneally from the thoracic paraortic area to the colonic serosa in experimental pigs (Keyting et aL, 1961). However, vastly more gas was present in the abdomen in Case 2 than in the small pneumothorax. Alternatively if the subclavian catheter is postulated to be related to the PC in any way, one must envisage continual indrawing of air around the outside of the catheter, followed by tracking to the mediastinum and subsequently to the abdomen. Although possible, we do not believe that this is a likely explanation, and we do not know o f reports from other authors describing this occurrence. Aphthous ulceration and a variable degree of diarrhoea are common during chemotherapy of acute myeloid leukaemia. This is presumed to occur because of damage to rapidly dividing mucosal cells. It seems possible to us that mucosal integrity is disrupted by the current chemotherapeutic regimes, and that intestinal gas is allowed to penetrate through the loose subserosal tissue to the serosal lining resulting in the linear shadows seen in Figs 2 and 3. A further possibility is suggested by Borns and Johnston (1973) that atrophy of lymph nodules (such as Peyer's patches) in the wall of the colon, results from treatment. This may result in mucosal defects and gas entry into the colonic wall. It is necessary to postulate an increased individual susceptibility in patients with PC as this condition is
178
CLINICAL RADIOLOGY
not more commonly encountered. It must be added, however, that the frequency and volume of diarrhoea in our patients was no greater than in similar patients without cystic pneumatosis. Increased colonic pressure, however, occurred in Case 1 as a result o f anal spasm. This immediately preceded the X-ray finding of intra-abdominal gas, and may be causally related. The cause of susceptibility in the other two patients eludes us.
CONCLUSION Having considered the possibility o f gas tracking from distant sites, infectiou~ causes, and having ruled out respiratory disorders° one is hard-pressed to define the source. Unfortunately, due to the patients' condition, full radiological examination of the gut was n o t possible at the time of the disorder. One can postulate that either the disease, the treatment, or a combination of both leads in susceptible patients to microscopic bowel mucosal defects. The passage o f
gas through the bowel wall into the retroperito~ea1 space then results in PC. REFERENCES
Borns, P. F. & Johnston, T. A- (1973). Indolent pneumatosis of the bowel wall associated with immune suppressive therapy.Annales de Radiolog~e, 16,163 -166. Colquhoun, J. (1965). Intramural gas in hollow viscera. Clinical Radiology, 16, 71-86. Jaffe, N., Carlson, D. H. & Vawter, G. F. (I972). Pneuraa. tosis cystoides intestinalis in acute leukaemia. Cancer.30, 239-243. Keyting, W. S., McCarver, R. R., Kovarik, J. L. & Daywitt, A. L. (1961). Pneumatosis intestinalis: a new concept. Radiology, 76,733-741. Koss, L- G. (1952). Abdominal gas cysts (pneumat0sis cystoides intestinorum hominis). Archives of Pathology, 53,523-547. Mueller, C. F., Morehead, R., Alter, A. J. & Michener, W, (1972). Pneumatosis intestinalis in collagen disorders. American Journal of Roentgenology, 115,300-305. Naeslund, J. (1924). Thesis (Uppsala). Cited by Koss, 1952. O'C0nnell, D. J. & Thompson, A. J. (1978). Pneumat0sis coli in non-Hodgkin's lymphoma. British Journal of Radiology, 51,203-205_
Fneumatosis Coli in Adult Acute Myeloid Leukaemia I), McCARTHY, I. H O L L A N D , J. P. L A V E N D E R and D. C A T O V S K Y
From the Departments of Haematology and Diagnostic Radiology and the MRC Leukaemia Unit, Royal postgraduate Medical School and Harnrnersmith Hospital, London Three cases of pneumatosis coli (PC) in adult patients w i t h acute m y e l o i d leukaemia seen over the last five years in Hammersmith Hospital are reported. A l t h o u g h definite conclusions are impossible, we suggest t h a t that pneumatosis could be due to damage to t h e b o w e l m u c o s a as a result o f the disease or the treatment. ]'he literature is reviewed and discussed in an inconclusive a t t e m p t to discover the source o f the gas.
PC is a condition where gas is present in the colonic wall and is an u n c o m m o n finding in general radiological practice. Various patterns o f intramural gas have been reported, of which PC represents one_ Colquhoun (1965) presents a useful classification into three groups - namely, cystic pneumatosis, 'interstitial e m p h y s e m a ' and cases resulting f r o m infection. PC seems to represent cystic pneumatosis confined to the colon. Many causes for PC have b e e n postulated. It is suggested, in patients with respiratory disease, t h a t respiratory obstruction produces alveolar rupture and pulmonary interstitial e m p h y s e m a . The gas t h e n tracks to the lung hilum, the m e d i a s t i n u m and the retroperitoneal space, gaining access to the colnic wall by tracking along the b l o o d vessels f r o m t h e retroperitoneal space (Keyting et al., 1961). The association with obstructive b o w e l lesions is p o o r l y u n d e r s t o o d but is presumed to be on the basis o f raised intraluminal pressure forcing gas through the bowel wall (Colquhoun, 1965). Recently there have been reports of PC w i t h collagen disorders (Mueller et al., 1972) and malignant l y m p h o m a (O'Connell and T h o m p s o n , 1978). In acute c h i l d h o o d leukaemias six patients were described (Jaffe et al., 1972). F o u r of these patients had an ulcerated or infiltrated GIT suggesting these defects as the portal of gas entry. We have been unable to find any r e p o r t e d w i t h adult acute m y e l o i d leukaemia (AML) and accordingly present the following three cases.
CASE REPORTS Case 1. A.M. a 51-year-old Caucasian woman, developed AML in October 1973. Although previously asthmatic she had been well and was receiving no medication for the previous 18 years. Physical examination, and radiological evaluation of chest and abdomen showed no abnormality. Iliac crest bone marrow aspirate- was hypercellular with 90% myeloblasts. Chemotherapy was instituted via a subclavian line and consisted of six courses of daunorubicin and
cytosine arabinoside. An oral antibiotic regime (FRACON) with framycycetin, colistin, nystatin tablets and elixir was also commenced to sterilise the gut. Initially during treatment the patient had an episode of air embolism due to the disconnection of the subclavian line, and also developed diarrhoea but with no blood or mucus passed per rectum. Aerobic and anaerobic stool culture showed only a light growth of lactobacilli. A month following the start of treatment she developed prolapsed haemorrhoids, anal spasm and abdominal distension. The latter continued and a plain film of the abdomen showed a large quantity of retroperitoneal and intraperitoneal gas. As she was not in remission further chemotherapy was given but with no effect and she developed pytexia, further abdominal distension with peritonism, and died. At autopsy extensive candidiasis was found involving the myocardium, lungs, liver, spleen, kidneys and the oesophageal mucosa but with sparing of the remaining GI tract. Ulceration at the gastro-oesophageal junction was noted. There were gas 'bubbles' revolving all layers of the gut wall and paracolic tissue, from the caecum to the splenic flexure. No perforation was found. Case 2. D.W., a 24-year-old Caucasian woman, developed AML in February 1972. There was no past history of illness. Chemotherapy with daunorubicin, and other cytotoxic agents achieved a complete remission and also achieved further remissions following relapses in March 1974 and December 1975. In February 1977 maintenance chemotherapy was discontinued. Following a relapse in December 1977, physical examination and chest radiography showed no abnormality. Her marrow contained 60% blast forms. FRACON was administered (as for Case 1). Chemotherapy via a subclavian line was commenced. Following insertion of the subclavian line a small right apical pneumothorax was seen on a chest radiograph_ Further treatment achieved therapeutic aphasia. During treatment the patient was nauseous and had diarrhoea and vomiting. Following treatment she developed a mild respiratory infection with a normal chest X-ray. Antibiotics were prescribed and when the respiratory tract infection was resolving she developed abdominal distension with excess flatus and diarrhoea. Surgical emphysema was noted at this time in her right supraclavicular fossa. This was confirmed on a chest X-ray which also showed gas under both hemidiaphragms (Fig. 1). No pneumothorax or mediastinal gas was seen. Abdominal films with decubitus views (obtained with portable apparatus as the patient was isolated due to neutropenia) showed both intraand retroperitoneal gas. Linear gas translucencies were also seen outlining the walls of the ascending and transverse colons (Fig. 2). A diagnosis of pneumatosis coli was made.
176
CLINICAL RADIOLOGY
Fig. 1 - Case 2- Chest with CVP line in situ and gas under b o t h hemidiaphragms,
Fig. 2 - Case 2. A b d o m e n with retroperitoneal gas and subserosal gas outlining the proximal colon.
Fig. 3 - Case 3. Upper a b d o m e n with retro- and intraperitoneal air_ Note linear subserosal gas in descending colon.
PNEUMATOSIS COLI As the patient's abdominal symptoms subsided, t h e radiological appearances resolved. No specific treatment was given. The condition did n o t recur with subsequent chemotheraPY" Case 3. S.G.M., an 18-year-old Caucasian man, presented ~vith AML in February 1977. Previously well, on examination he was noted to be pale with splenomegaly and fundal haemorrhages. An iliac crest marrow aspirate was hypercellular with 85% blast cells. A chest X-ray at this time was normal. Chemotherapy was commenced with cyclophoshamide, vincristine, and other cytotoxic agents, along with RACON- Following this he became pyrexial and was treated with intravenous antibiotics. A second course o f chemotheraPY 10 days later failed to induce a remission. Aphthous ulceration was noted at this time. It was then decided to administer further chemotherapy via a subclavian line. A minor air embolism occurred during insertion of the line. Following chemotherapy the patient developed diarrhoea with abdominal distension and excessive flatus. Stool culture grow E. coil However, a chest radiograph showed gas under both hemidiaphragms, and abdominal radiographs showed a large quantity o f retroperitoneal gas. Linear gas translucencies were seen outlining the caecum, ascending, transverse and upper descending colon (Fig. 3). Small gas-filled cysts were also noted within the colonic wall. A diagnosis o f PC was made. A gastrografin meal showed a normal upper gastrointestinal tract. The symptoms and the radiotogical findings subsequently resolved over the following month and no recurrence occurred with subsequent chemotherapy- In April 1978, while in remission, the patient developed hepatitis B-antigen positive hepatitis, hepatic coma and died. Autopsy was not performed.
DISCUSSION Many causes for PC have been enumerated, but the occurrence of minor structural bowel abnormalities resulting from either the disease or the treatment ia cases of leukaemia is, in our opinion, most likely to account for the development o f the pneumatosis coll.
It can be seen that when PC occurred all three cases had AML; were aplastic as a result of treatment; were receiving gut sterilising antibiotics; had diarrhoea, abdominal distension and intraperitoneal gas. Air embolism occurred in Cases 1 and 3 and pneumothorax in Case 2. Case 1 was diagnosed at post-mortem examination and Cases 2 and 3 were recognised because of classical X-ray features. Case 1 differed from the other two patients in that she had disseminated candidiasis at autopsy. Candidal ulceration was found in the oesophagus, but there was no evidence of candidal infection lower in the intestinal tract. The candidal ulcer in the oesophagus is an unlikely site for gas entry as no cysts were present in the stomach at autopsy and there was no evidence of oesophageal perforation. I.eukaemic infiltration of the intestinal mucosa with .Consequent damage to its integrity is also possible tn this patient but was not demonstrated at autopsy. As the three patients were aplastic when the PC
177
developed, it may be that leukaemic bowel involvement had been present and resolved with chemotherapy. However, rio bowel symptoms were present in any patient at initial presentation. Infection with gas-forming bacteria resistant to the gut sterilisation regime must be mentioned as a possibility. However, only light growths of E. coli and lactobacilli occurred in stool cultures. The large amount of gas seen in the retroperitoneal space (Figs 1, 2) - separating diaphragm from liver if due to bacteria, could only be explained by massive gasforming infection, or by rupture o f a cyst or cysts, resulting in intestin~d perforation. Although Case 1 exhibited peritonism, no evidence of perforation was found and no peritonism was present in the other patients. Also file theoretical background supporting an infective cause is not strong, and is based on the isolation of a gas-forming E. coli from pigs with cystic pneumatosis and the failure to isolate it from normal pigs (Naeslund, 1924). We must also consider that all patients had air introduced as a result of insertion of subclavian intravenous lines, but it is difficult to conceive how air in the blood stream could be responsible for the condition. Pneumothorax could certainly be responsible for formation of cysts, as air has been demonstrated to migrate retroperitoneally from the thoracic paraortic area to the colonic serosa in experimental pigs (Keyting et aL, 1961). However, vastly more gas was present in the abdomen in Case 2 than in the small pneumothorax. Alternatively if the subclavian catheter is postulated to be related to the PC in any way, one must envisage continual indrawing of air around the outside of the catheter, followed by tracking to the mediastinum and subsequently to the abdomen. Although possible, we do not believe that this is a likely explanation, and we do not know o f reports from other authors describing this occurrence. Aphthous ulceration and a variable degree of diarrhoea are common during chemotherapy of acute myeloid leukaemia. This is presumed to occur because of damage to rapidly dividing mucosal cells. It seems possible to us that mucosal integrity is disrupted by the current chemotherapeutic regimes, and that intestinal gas is allowed to penetrate through the loose subserosal tissue to the serosal lining resulting in the linear shadows seen in Figs 2 and 3. A further possibility is suggested by Borns and Johnston (1973) that atrophy of lymph nodules (such as Peyer's patches) in the wall of the colon, results from treatment. This may result in mucosal defects and gas entry into the colonic wall. It is necessary to postulate an increased individual susceptibility in patients with PC as this condition is
178
CLINICAL RADIOLOGY
not more commonly encountered. It must be added, however, that the frequency and volume of diarrhoea in our patients was no greater than in similar patients without cystic pneumatosis. Increased colonic pressure, however, occurred in Case 1 as a result o f anal spasm. This immediately preceded the X-ray finding of intra-abdominal gas, and may be causally related. The cause of susceptibility in the other two patients eludes us.
CONCLUSION Having considered the possibility o f gas tracking from distant sites, infectiou~ causes, and having ruled out respiratory disorders° one is hard-pressed to define the source. Unfortunately, due to the patients' condition, full radiological examination of the gut was n o t possible at the time of the disorder. One can postulate that either the disease, the treatment, or a combination of both leads in susceptible patients to microscopic bowel mucosal defects. The passage o f
gas through the bowel wall into the retroperito~ea1 space then results in PC. REFERENCES
Borns, P. F. & Johnston, T. A- (1973). Indolent pneumatosis of the bowel wall associated with immune suppressive therapy.Annales de Radiolog~e, 16,163 -166. Colquhoun, J. (1965). Intramural gas in hollow viscera. Clinical Radiology, 16, 71-86. Jaffe, N., Carlson, D. H. & Vawter, G. F. (I972). Pneuraa. tosis cystoides intestinalis in acute leukaemia. Cancer.30, 239-243. Keyting, W. S., McCarver, R. R., Kovarik, J. L. & Daywitt, A. L. (1961). Pneumatosis intestinalis: a new concept. Radiology, 76,733-741. Koss, L- G. (1952). Abdominal gas cysts (pneumat0sis cystoides intestinorum hominis). Archives of Pathology, 53,523-547. Mueller, C. F., Morehead, R., Alter, A. J. & Michener, W, (1972). Pneumatosis intestinalis in collagen disorders. American Journal of Roentgenology, 115,300-305. Naeslund, J. (1924). Thesis (Uppsala). Cited by Koss, 1952. O'C0nnell, D. J. & Thompson, A. J. (1978). Pneumat0sis coli in non-Hodgkin's lymphoma. British Journal of Radiology, 51,203-205_