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Renal transplant recipient experiencing pneumatosis cystoides intestinalis: a case report
OTHERS
Renal Transplant Recipient Experiencing Pneumatosis Cystoides Intestinalis: A Case Report K. Nakamura, Y. Ohmori, M. Okamoto, K. Akioka, H. Ushigome, Y. Kadotani, and N. Yoshimura
P
NEUMATOSIS CYSTOIDES INTESTINALIS (PCI) is a relatively rare condition characterized by multiple intramural pockets of gas involving any portion of the gastrointestinal tract and occasionally the mesenteric attachments. Pneumatosis in adults frequently has a benign course and prognosis, depending on associated diseases of the gastrointestinal pulmonary organs. Infantile pneumatosis intestinalis associated with necrotizing enteritis, however, is a more serious condition and has a high mortality rate. The present report described a case of renal transplantation with PCI. CASE REPORT The recipient was a 56-year-old male with chronic renal failure due to diabetic nephropathy. The donor was his 56-year-old healthy wife with good kidney function (serum creatinine 0.6 mg/dL), a compatible blood type, a complete HLA mismatch, and a negative crossmatch test. The total ischemic time was 48 minutes. The immunosuppressive treatment consisted of tacrolimus (FK), prednisolone, mizoribin, and 15-deoxyspergualin. Our usual immunosuppression regimen for a living-related kidney transplant has included an initial dose of FK (0.3 mg/kg per day) or cyclosporine (CsA, 12 mg/kg per day) administered orally for 2 days before transplant; FK (0.1 mg/kg per day) or CsA (4 mg/kg per day) administered continuously intravenously on the day of transplant, followed by FK (0.3 mg/d) or CsA (12 mg/d) orally for 3 weeks. Dose of FK or CsA was adjusted by the trough level. A bolus dose of 500 mg methylprednisolone was administrated on the day of transplant, followed by 50 mg/d of prednisolone on days 0 to 3. Prednisolone was reduced every week from 40, 30, 25, 20, 15, to 10 mg/d. Azathioprine (1 to 1.5 mg/kg per day) or mycophenolate mofetil (20 to 25 mg/kg per day) was added on day 21. The recipient was discharged on postoperative day 39, when his serum creatinine level reached 1.44 mg/dL. After 6 months, when he had an examination of chest x-ray, free air in peritoneal cavity was seen. Although there were no symptoms attributable to © 2003 by Elsevier Science Inc. 360 Park Avenue South, New York, NY 10010-1710 Transplantation Proceedings, 35, 297–299 (2003)
intestinal perforation, further examinations, including computed tomography, barium enema, and colonoscopy, showed intramucosal pneumatosis from the cecum to the transverse colon (Fig 1). The patient was diagnosed as PCI, and has been followed to the present.
DISCUSSION
One of the main characteristics of PCI is gas forming cysts under the serosa of the involved segment of intestinal wall. The symptoms of PCI in adults are in no sense specific; they may be an expression of the concomitant disease with which pneumatosis is often associated. Abdominal signs may be absent, although mild abdominal tenderness may be detected. In infants, PCI is frequently associated with septicemia and shock because of its common association with necrotizing enterocolitis in this age group. Neither the etiology nor the natural history of PCI is well understood. Probably more than one mechanism is responsible for the formation of gas cysts. The various theories of etiology have been grouped as either mechanical or bacterial. Mechanical theory holds that a break in the continuity of the mucosa permits air to pass from the intestinal lumen to the submucosal spaces.1 On the other hand, bacterial theory is based on clinical as well as experimental evidence From the Department of Organ Transplant and Endocrine Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan. Supported (in part) by a Grant-in-Aid for Research on Human Genome and tissue engineering food biotechnology and health sciences research grants, Ministry of Health, Labour and Welfare, Japan. Address reprint requests to Dr K. Nakamura, Department of Organ Transplant and Endocrine Surgery, Kyoto Prefectural University of Medicine, 465 Kawaramachi, Hirokoji, Kamigyo-ku, Kyoto city, Kyoto 602-8566, Japan. 0041-1345/03/$–see front matter doi:10.1016/S0041-1345(02)03915-5 297
298
NAKAMURA, OHMORI, OKAMOTO ET AL
Fig 1. (A) Supine view of the abdomen with barium enema shows air in the wall of transverse colon (arrows). (B) Colonoscopic appearance of the transverse colon shows numerous mucosal elevations with smooth surface, which are due to air-filled intramural cysts.
that the gas produced in pneumatosis is of bacterial origin. Bacteria are believed to be responsible for the gas cysts in these infants, with increased permeability of the intestinal mucosa to gas-forming bacteria, perhaps being related to prematurity, malnutrition, extracellular fluid depletion, and severe enteritis.2 In radiographic appearance on plain films, PCI appears as radiolucent areas within the bowel wall, which must be differentiated from luminal intestinal gas.3 The radiolucency may be linear, curvilinear, or appear as grapelike clusters or tiny bubbles.3 There can be discontinuous areas of involvement, and each region may cover a few inches to several feet.4 In all cases, the radiolucencies follow the bowel contour. Obtaining films with the patient in different dependent positions can help to distinguish PCI from intraluminal gas. Alternatively, barium contrast or computed tomography (CT) studies can be utilized to confirm the diagnosis. CT is more sensitive than plain radiography for PCI detection, and lung window settings can be especially helpful in identifying small pneumatosis cysts.5 On CT, PCI appears as intramural gas parallel to the bowel wall. Unlike intraluminal gas, PCI can be located on the dependent aspect of the bowel and does not contain air-fluid levels.6 Smerud et al reported that CT alone was diagnostic in 9 of 23 (39%) patients with ischemic bowel. Plain films were diagnostic in 30% of these patients, but 65% of them had CT or plain film findings that were consistent with infarction.7 Administration of oxygen at high concentrations has been shown to be effective in resolving pneumatosis cysts.8 Oxygen administration may eradicate the cysts by reducing the partial pressure of gases other than oxygen within the blood, thereby increasing the gradient between the blood and the cysts, which are thought to contain gases other than oxygen.8 Another theory holds that the high oxygen concentration kills bacteria that are believed by some to be responsible for cyst formation.8 Because anaerobic bacteria have been suggested to be
responsible for formation of pneumatosis cysts, metronidazole has also been used for treatment of PCI.9 Unlike oxygen therapy, metronidazole may be administered on an outpatient basis. In the present case, PCI was discovered after renal transplantation. Our patient had no symptoms and signs, although there was free air in the peritoneal cavity. It is also unclear when PCI formed in the submucosa of colon. This patient had no examination of barium enema or colonoscopy up to the time of discovery of PCI. Recent studies have also demonstrated that PCI occurs in association with chronic obstructive pulmonary disease (COPD),10 and that a number of cases of PCI have been reported in Japanese factory workers exposed to the degreasing agent, trichloroethylene (TCE).11 But this patient had neither COPD nor other pulmonary diseases, and he had not been exposed to TCE in the past. We found no cause for PCI corresponding to reported various theories. We selected oxygen therapy because our patient had no symptoms; however, no improvement was found. We believe that more aggressive treatment was not necessary in this case because PCI in adults is usually benign. There was no serious complication, and therefore we continue to follow this patient.
CONCLUSIONS
PCI is a relatively rare finding with a broad differential. The condition also may be recognized as a benign cause of pneumatoperitoneum. The findings emphasize the benign course in most patients who present with pneumatosis. However, PCI may often be misdiagnosed as intestinal perforation, with an emergency surgical treatment being performed. Recent reports have demonstrated that corticosteroid administration might be associated with PCI.12 When transplanted patients have free air in the peritoneal cavity, it is necessary to consider the possibility of PCI.
TRANSPLANT RECIPIENT WITH PCI
REFERENCES 1. Kay-Butler JJ: Gut 3:267, 1962 2. Stevenson DK, Graham S, Stevenson JK: Adv Pediatr 27:319, 1980 3. Ecker JA, William RG, Clay KL: Am J Gastroenterol 56:125, 1971 4. Marshak RH, Lindner AE, Makalansky D: Gastrointest Radiol 2:85, 1977 5. Feczko PJ, Mezwa DG, Farah MC, et al: RadioGraphics 12:1069, 1992
299 6. Sequeira W: Semi Arthritis Rheum 19:269, 1990 7. Smerud MJ, Johnson CD, Stephans DH: AJR 154:99, 1990 8. Grieve DA, Unsworth IP: Aust NZ J Surg 61:423, 1991 9. Goulet JR, Hurtubice M, Sene´cal JL: Clin Exp Rheumatol 6:81, 1988 10. Keyting WS, McCarver RR, Kovarik JL, et al: Radiology 76:733, 1961 11. Hosomi N, Yoshioka H, Kuroda C, et al: Abdom Imag 19:137, 1994 12. Cabrera GE, Scopelitis E, Cuellar ML, et al: Clin Rheumatol 13:312, 1994
Renal Transplant Recipient Experiencing Pneumatosis Cystoides Intestinalis: A Case Report K. Nakamura, Y. Ohmori, M. Okamoto, K. Akioka, H. Ushigome, Y. Kadotani, and N. Yoshimura
P
NEUMATOSIS CYSTOIDES INTESTINALIS (PCI) is a relatively rare condition characterized by multiple intramural pockets of gas involving any portion of the gastrointestinal tract and occasionally the mesenteric attachments. Pneumatosis in adults frequently has a benign course and prognosis, depending on associated diseases of the gastrointestinal pulmonary organs. Infantile pneumatosis intestinalis associated with necrotizing enteritis, however, is a more serious condition and has a high mortality rate. The present report described a case of renal transplantation with PCI. CASE REPORT The recipient was a 56-year-old male with chronic renal failure due to diabetic nephropathy. The donor was his 56-year-old healthy wife with good kidney function (serum creatinine 0.6 mg/dL), a compatible blood type, a complete HLA mismatch, and a negative crossmatch test. The total ischemic time was 48 minutes. The immunosuppressive treatment consisted of tacrolimus (FK), prednisolone, mizoribin, and 15-deoxyspergualin. Our usual immunosuppression regimen for a living-related kidney transplant has included an initial dose of FK (0.3 mg/kg per day) or cyclosporine (CsA, 12 mg/kg per day) administered orally for 2 days before transplant; FK (0.1 mg/kg per day) or CsA (4 mg/kg per day) administered continuously intravenously on the day of transplant, followed by FK (0.3 mg/d) or CsA (12 mg/d) orally for 3 weeks. Dose of FK or CsA was adjusted by the trough level. A bolus dose of 500 mg methylprednisolone was administrated on the day of transplant, followed by 50 mg/d of prednisolone on days 0 to 3. Prednisolone was reduced every week from 40, 30, 25, 20, 15, to 10 mg/d. Azathioprine (1 to 1.5 mg/kg per day) or mycophenolate mofetil (20 to 25 mg/kg per day) was added on day 21. The recipient was discharged on postoperative day 39, when his serum creatinine level reached 1.44 mg/dL. After 6 months, when he had an examination of chest x-ray, free air in peritoneal cavity was seen. Although there were no symptoms attributable to © 2003 by Elsevier Science Inc. 360 Park Avenue South, New York, NY 10010-1710 Transplantation Proceedings, 35, 297–299 (2003)
intestinal perforation, further examinations, including computed tomography, barium enema, and colonoscopy, showed intramucosal pneumatosis from the cecum to the transverse colon (Fig 1). The patient was diagnosed as PCI, and has been followed to the present.
DISCUSSION
One of the main characteristics of PCI is gas forming cysts under the serosa of the involved segment of intestinal wall. The symptoms of PCI in adults are in no sense specific; they may be an expression of the concomitant disease with which pneumatosis is often associated. Abdominal signs may be absent, although mild abdominal tenderness may be detected. In infants, PCI is frequently associated with septicemia and shock because of its common association with necrotizing enterocolitis in this age group. Neither the etiology nor the natural history of PCI is well understood. Probably more than one mechanism is responsible for the formation of gas cysts. The various theories of etiology have been grouped as either mechanical or bacterial. Mechanical theory holds that a break in the continuity of the mucosa permits air to pass from the intestinal lumen to the submucosal spaces.1 On the other hand, bacterial theory is based on clinical as well as experimental evidence From the Department of Organ Transplant and Endocrine Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan. Supported (in part) by a Grant-in-Aid for Research on Human Genome and tissue engineering food biotechnology and health sciences research grants, Ministry of Health, Labour and Welfare, Japan. Address reprint requests to Dr K. Nakamura, Department of Organ Transplant and Endocrine Surgery, Kyoto Prefectural University of Medicine, 465 Kawaramachi, Hirokoji, Kamigyo-ku, Kyoto city, Kyoto 602-8566, Japan. 0041-1345/03/$–see front matter doi:10.1016/S0041-1345(02)03915-5 297
298
NAKAMURA, OHMORI, OKAMOTO ET AL
Fig 1. (A) Supine view of the abdomen with barium enema shows air in the wall of transverse colon (arrows). (B) Colonoscopic appearance of the transverse colon shows numerous mucosal elevations with smooth surface, which are due to air-filled intramural cysts.
that the gas produced in pneumatosis is of bacterial origin. Bacteria are believed to be responsible for the gas cysts in these infants, with increased permeability of the intestinal mucosa to gas-forming bacteria, perhaps being related to prematurity, malnutrition, extracellular fluid depletion, and severe enteritis.2 In radiographic appearance on plain films, PCI appears as radiolucent areas within the bowel wall, which must be differentiated from luminal intestinal gas.3 The radiolucency may be linear, curvilinear, or appear as grapelike clusters or tiny bubbles.3 There can be discontinuous areas of involvement, and each region may cover a few inches to several feet.4 In all cases, the radiolucencies follow the bowel contour. Obtaining films with the patient in different dependent positions can help to distinguish PCI from intraluminal gas. Alternatively, barium contrast or computed tomography (CT) studies can be utilized to confirm the diagnosis. CT is more sensitive than plain radiography for PCI detection, and lung window settings can be especially helpful in identifying small pneumatosis cysts.5 On CT, PCI appears as intramural gas parallel to the bowel wall. Unlike intraluminal gas, PCI can be located on the dependent aspect of the bowel and does not contain air-fluid levels.6 Smerud et al reported that CT alone was diagnostic in 9 of 23 (39%) patients with ischemic bowel. Plain films were diagnostic in 30% of these patients, but 65% of them had CT or plain film findings that were consistent with infarction.7 Administration of oxygen at high concentrations has been shown to be effective in resolving pneumatosis cysts.8 Oxygen administration may eradicate the cysts by reducing the partial pressure of gases other than oxygen within the blood, thereby increasing the gradient between the blood and the cysts, which are thought to contain gases other than oxygen.8 Another theory holds that the high oxygen concentration kills bacteria that are believed by some to be responsible for cyst formation.8 Because anaerobic bacteria have been suggested to be
responsible for formation of pneumatosis cysts, metronidazole has also been used for treatment of PCI.9 Unlike oxygen therapy, metronidazole may be administered on an outpatient basis. In the present case, PCI was discovered after renal transplantation. Our patient had no symptoms and signs, although there was free air in the peritoneal cavity. It is also unclear when PCI formed in the submucosa of colon. This patient had no examination of barium enema or colonoscopy up to the time of discovery of PCI. Recent studies have also demonstrated that PCI occurs in association with chronic obstructive pulmonary disease (COPD),10 and that a number of cases of PCI have been reported in Japanese factory workers exposed to the degreasing agent, trichloroethylene (TCE).11 But this patient had neither COPD nor other pulmonary diseases, and he had not been exposed to TCE in the past. We found no cause for PCI corresponding to reported various theories. We selected oxygen therapy because our patient had no symptoms; however, no improvement was found. We believe that more aggressive treatment was not necessary in this case because PCI in adults is usually benign. There was no serious complication, and therefore we continue to follow this patient.
CONCLUSIONS
PCI is a relatively rare finding with a broad differential. The condition also may be recognized as a benign cause of pneumatoperitoneum. The findings emphasize the benign course in most patients who present with pneumatosis. However, PCI may often be misdiagnosed as intestinal perforation, with an emergency surgical treatment being performed. Recent reports have demonstrated that corticosteroid administration might be associated with PCI.12 When transplanted patients have free air in the peritoneal cavity, it is necessary to consider the possibility of PCI.
TRANSPLANT RECIPIENT WITH PCI
REFERENCES 1. Kay-Butler JJ: Gut 3:267, 1962 2. Stevenson DK, Graham S, Stevenson JK: Adv Pediatr 27:319, 1980 3. Ecker JA, William RG, Clay KL: Am J Gastroenterol 56:125, 1971 4. Marshak RH, Lindner AE, Makalansky D: Gastrointest Radiol 2:85, 1977 5. Feczko PJ, Mezwa DG, Farah MC, et al: RadioGraphics 12:1069, 1992
299 6. Sequeira W: Semi Arthritis Rheum 19:269, 1990 7. Smerud MJ, Johnson CD, Stephans DH: AJR 154:99, 1990 8. Grieve DA, Unsworth IP: Aust NZ J Surg 61:423, 1991 9. Goulet JR, Hurtubice M, Sene´cal JL: Clin Exp Rheumatol 6:81, 1988 10. Keyting WS, McCarver RR, Kovarik JL, et al: Radiology 76:733, 1961 11. Hosomi N, Yoshioka H, Kuroda C, et al: Abdom Imag 19:137, 1994 12. Cabrera GE, Scopelitis E, Cuellar ML, et al: Clin Rheumatol 13:312, 1994