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MARS dialysis in the state of chronic rejection in a liver transplant recipient
THE AMERICAN JOURNAL OF GASTROENTEROLOGY © 2002 by Am. Coll. of Gastroenterology Published by Elsevier Science Inc.
Vol. 97, No. 4, 2002 ISSN 0002-9270/02/$22.00
LETTERS TO THE EDITOR MARS Dialysis in the State of Chronic Rejection in a Liver Transplant Recipient TO THE EDITOR: The long term survival of liver transplant recipients is steadily improving. However, there is still a lack of treatment options in subjects who suffer from chronic rejection of their liver grafts once retransplantation is contraindicated. Molecular absorbent recycling system (MARS) dialysis was introduced in 1993 for bridging patients with acute liver failure. It uses albumin as a carrier for potential toxic substrates due to liver failure (1, 2). We report on a case of 7-month follow-up of chronic MARS dialysis in a 70-yr-old patient with advanced chronic rejection 9 yr after liver transplantation. In 1992 liver transplantation was performed because of end-stage primary biliary cirrhosis. After an initially uncomplicated follow-up in 1994 choledochojejunostomy was required because of stenosis of the common bile duct (ischemic bile duct lesion) accompanied by choledocholithiasis. Chronic rejection was first histologically documented in 1995. Immunosupressive therapy was changed from cyclosporine to tacrolimus. Progressive stenosis of the common bile duct was successfully treated with stent implantation. However, endoscopic cholangiography confirmed the progressive chronic rejection with vanishing bile duct syndrome. Meanwhile, the diagnosis of two carcinomas excluded the patient from retransplantation. Prostatic
carcinoma was diagnosed in 1996, followed by diagnosis of dermatological carcinoma in 1998. The patient developed intractable pruritus. Bilirubin levels were approximately 9 mg/dl in 1998 and 1999. In August, 2000 a further increase of cholestatic enzymes and bilirubin was observed. We performed another liver biopsy. Only in three of 14 portal fields were biliary ducts seen. These ducts had advanced cellular alterations. In addition, fibrosis, piecemeal necroses, and inflammatory infiltration were present. The maximum value for bilirubin was 31.5 mg/dl. The liver synthesis parameters albumin (3.5 g/L) and PT (72%) were still in the lower normal ranges. Therefore, we decided to initiate MARS dialysis to potentially support the detoxification function of the liver via the hepatobiliary pathway. Already the first treatment resulted in an improvement of both mental and physical states. The patient also reported a marked diminishment of pruritus. We administered MARS within the 1st wk three times and continued this treatment strategy once per month (Fig. 1). Currently, the number of MARS dialyses are adapted to the clinical symptoms of the patient. Interestingly, the quantitation of bile acids in serum failed to substantiate the clinical success of this therapeutic approach. A marked decrease after MARS was followed by an early relapse (Fig. 1). Until now, MARS dialysis has been performed to overcome complications of acute onset of liver failure (e.g., encephalopathy, hepatorenal syndrome, bridging for liver
Figure 1. Each treatment with MARS dialysis is indicated with an arrow. The time course and this treatment’s impact on the serum concentrations of bilirubin (f) and bile acids (●) are illustrated.
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Letters to the Editor
AJG – Vol. 97, No. 4, 2002
transplantation). This is the first report on the successful use of MARS dialysis in the context of a therapeutic option in a chronic graft rejection state. We believe that MARS dialysis prolonged the subject’s life and improved its quality. Therefore, we propose this procedure as a long term treatment option in chronic liver transplant rejection once retransplantation is contraindicated. Prospective studies are required to confirm our observation. G. Schachschal, M.D. S. Morgera, M.D. S. Ku¨pferling, M.D. H. H.-J. Schmidt, M.D. H. Lochs, M.D. Departments for Gastroenterology, Hepatology, and Nephrology Universitatsklinikum Charite´ Campus Mitte Berlin, Germany
REFERENCES 1. Stange J, Mitzner SR, Risler T, et al. Molecular adsorbent recycling system (MARS): Clinical results of a new membranebased blood purification system for bioartificial liver support. Artif Organs 1999;23:319 –30. 2. Stange J, Mitzner SR, Klammt S, et al. Liver support by extracorporal blood purification: A clinical observation. Liver Transpl 2000;6:603–13. Reprint requests and correspondence: Hartmut H.-J., Schmidt, M.D., Gastroenterologie, Hepatologie and Endokrinologie, Medizinische Klinik mit Schwerpunkt, Universitatsklinikum Charite, D-10098 Berlin, Germany. Received Aug. 22, 2001; accepted Sep. 14, 2001.
GI Metastases From Melanoma: A Case Report TO THE EDITOR: Metastatic tumors to the GI tract are infrequent. In series of autopsies their prevalence was found to be 1– 4% overall (1). When found, they come most commonly from lung cancer, breast cancer, or melanoma (1). Metastases from malignant melanoma to the GI tract are diagnosed antemortem in only 1.5– 4.4% of the patients affected from the primitive cutaneous tumor (2), but are found in up to 58% of postmortem specimens from patients with melanoma (2, 3). We think that a case of solitary gastric metastasis from malignant melanoma we recently observed deserves some comment from the point of view of practical management and appropriate choice of the imaging technique. A 58-yr-old woman was followed up because of a right leg malignant melanoma diagnosed 20 yr earlier. In May, 2001 she presented to our day-hospital for clinical assessment of a moderate anemia, discovered 6 months earlier. Two days before the day-hospital workup she had complained of episodic alimentary vomiting. On physical ex-
Figure 1. A 3-cm, reddish, soft sessile mass found on the anterior side of the gastric body just beneath the cardia.
amination, only tenderness in the right iliac fossa and slight cutaneous pallor were found. An ultrasonographic examination of the upper abdomen did not reveal any abnormal finding. Hb was 9 g/dl, with microcytosis and hypochromia of the red cells. The erythrocyte sedimentation rate was 64 mm. Liver function tests were normal. An esophagogastroduodenoscopy was performed, and a 3-cm, reddish, soft sessile mass was found on the anterior side of the gastric body just beneath the cardia (Fig. 1). The lesion was not actively bleeding and did not show brownish spots. Biopsy specimens revealed metastases from pigmented malignant melanoma. Histochemistry was positive for S100 and CD 45. As part of metastatic localizations, a total body CT scan and positron emission tomography (PET) were performed. A contrast-enhanced CT scan was negative, whereas PET showed areas of abnormal fixation in the periumbilical, left flank, splenic flexure, supravescical, and hypogastric regions, from secondary intestinal localizations of the primitive malignant melanoma. The patient underwent a surgical intervention of multiple ileal resections and ablation of the gastric mass. Postoperative examination of the surgical specimens confirmed the diagnosis. The patient was regularly followed up. GI melanoma is, from a practical point of view, a matter of metastatic tumor, because only anecdotal and questionable reports deal with the problem of primitive forms (4). In our case, the patient’s anemia and personal history data addressed, with a high degree of suspicion, a possible GI metastasis from malignant melanoma. Most patients with upper GI metastases from melanoma are asymptomatic, but when symptoms are present, chronic anemia or acute upper GI bleeding is the most common manifestation (1, 2). In some reports, macroscopic appearances of gastric lesions
Vol. 97, No. 4, 2002 ISSN 0002-9270/02/$22.00
LETTERS TO THE EDITOR MARS Dialysis in the State of Chronic Rejection in a Liver Transplant Recipient TO THE EDITOR: The long term survival of liver transplant recipients is steadily improving. However, there is still a lack of treatment options in subjects who suffer from chronic rejection of their liver grafts once retransplantation is contraindicated. Molecular absorbent recycling system (MARS) dialysis was introduced in 1993 for bridging patients with acute liver failure. It uses albumin as a carrier for potential toxic substrates due to liver failure (1, 2). We report on a case of 7-month follow-up of chronic MARS dialysis in a 70-yr-old patient with advanced chronic rejection 9 yr after liver transplantation. In 1992 liver transplantation was performed because of end-stage primary biliary cirrhosis. After an initially uncomplicated follow-up in 1994 choledochojejunostomy was required because of stenosis of the common bile duct (ischemic bile duct lesion) accompanied by choledocholithiasis. Chronic rejection was first histologically documented in 1995. Immunosupressive therapy was changed from cyclosporine to tacrolimus. Progressive stenosis of the common bile duct was successfully treated with stent implantation. However, endoscopic cholangiography confirmed the progressive chronic rejection with vanishing bile duct syndrome. Meanwhile, the diagnosis of two carcinomas excluded the patient from retransplantation. Prostatic
carcinoma was diagnosed in 1996, followed by diagnosis of dermatological carcinoma in 1998. The patient developed intractable pruritus. Bilirubin levels were approximately 9 mg/dl in 1998 and 1999. In August, 2000 a further increase of cholestatic enzymes and bilirubin was observed. We performed another liver biopsy. Only in three of 14 portal fields were biliary ducts seen. These ducts had advanced cellular alterations. In addition, fibrosis, piecemeal necroses, and inflammatory infiltration were present. The maximum value for bilirubin was 31.5 mg/dl. The liver synthesis parameters albumin (3.5 g/L) and PT (72%) were still in the lower normal ranges. Therefore, we decided to initiate MARS dialysis to potentially support the detoxification function of the liver via the hepatobiliary pathway. Already the first treatment resulted in an improvement of both mental and physical states. The patient also reported a marked diminishment of pruritus. We administered MARS within the 1st wk three times and continued this treatment strategy once per month (Fig. 1). Currently, the number of MARS dialyses are adapted to the clinical symptoms of the patient. Interestingly, the quantitation of bile acids in serum failed to substantiate the clinical success of this therapeutic approach. A marked decrease after MARS was followed by an early relapse (Fig. 1). Until now, MARS dialysis has been performed to overcome complications of acute onset of liver failure (e.g., encephalopathy, hepatorenal syndrome, bridging for liver
Figure 1. Each treatment with MARS dialysis is indicated with an arrow. The time course and this treatment’s impact on the serum concentrations of bilirubin (f) and bile acids (●) are illustrated.
1060
Letters to the Editor
AJG – Vol. 97, No. 4, 2002
transplantation). This is the first report on the successful use of MARS dialysis in the context of a therapeutic option in a chronic graft rejection state. We believe that MARS dialysis prolonged the subject’s life and improved its quality. Therefore, we propose this procedure as a long term treatment option in chronic liver transplant rejection once retransplantation is contraindicated. Prospective studies are required to confirm our observation. G. Schachschal, M.D. S. Morgera, M.D. S. Ku¨pferling, M.D. H. H.-J. Schmidt, M.D. H. Lochs, M.D. Departments for Gastroenterology, Hepatology, and Nephrology Universitatsklinikum Charite´ Campus Mitte Berlin, Germany
REFERENCES 1. Stange J, Mitzner SR, Risler T, et al. Molecular adsorbent recycling system (MARS): Clinical results of a new membranebased blood purification system for bioartificial liver support. Artif Organs 1999;23:319 –30. 2. Stange J, Mitzner SR, Klammt S, et al. Liver support by extracorporal blood purification: A clinical observation. Liver Transpl 2000;6:603–13. Reprint requests and correspondence: Hartmut H.-J., Schmidt, M.D., Gastroenterologie, Hepatologie and Endokrinologie, Medizinische Klinik mit Schwerpunkt, Universitatsklinikum Charite, D-10098 Berlin, Germany. Received Aug. 22, 2001; accepted Sep. 14, 2001.
GI Metastases From Melanoma: A Case Report TO THE EDITOR: Metastatic tumors to the GI tract are infrequent. In series of autopsies their prevalence was found to be 1– 4% overall (1). When found, they come most commonly from lung cancer, breast cancer, or melanoma (1). Metastases from malignant melanoma to the GI tract are diagnosed antemortem in only 1.5– 4.4% of the patients affected from the primitive cutaneous tumor (2), but are found in up to 58% of postmortem specimens from patients with melanoma (2, 3). We think that a case of solitary gastric metastasis from malignant melanoma we recently observed deserves some comment from the point of view of practical management and appropriate choice of the imaging technique. A 58-yr-old woman was followed up because of a right leg malignant melanoma diagnosed 20 yr earlier. In May, 2001 she presented to our day-hospital for clinical assessment of a moderate anemia, discovered 6 months earlier. Two days before the day-hospital workup she had complained of episodic alimentary vomiting. On physical ex-
Figure 1. A 3-cm, reddish, soft sessile mass found on the anterior side of the gastric body just beneath the cardia.
amination, only tenderness in the right iliac fossa and slight cutaneous pallor were found. An ultrasonographic examination of the upper abdomen did not reveal any abnormal finding. Hb was 9 g/dl, with microcytosis and hypochromia of the red cells. The erythrocyte sedimentation rate was 64 mm. Liver function tests were normal. An esophagogastroduodenoscopy was performed, and a 3-cm, reddish, soft sessile mass was found on the anterior side of the gastric body just beneath the cardia (Fig. 1). The lesion was not actively bleeding and did not show brownish spots. Biopsy specimens revealed metastases from pigmented malignant melanoma. Histochemistry was positive for S100 and CD 45. As part of metastatic localizations, a total body CT scan and positron emission tomography (PET) were performed. A contrast-enhanced CT scan was negative, whereas PET showed areas of abnormal fixation in the periumbilical, left flank, splenic flexure, supravescical, and hypogastric regions, from secondary intestinal localizations of the primitive malignant melanoma. The patient underwent a surgical intervention of multiple ileal resections and ablation of the gastric mass. Postoperative examination of the surgical specimens confirmed the diagnosis. The patient was regularly followed up. GI melanoma is, from a practical point of view, a matter of metastatic tumor, because only anecdotal and questionable reports deal with the problem of primitive forms (4). In our case, the patient’s anemia and personal history data addressed, with a high degree of suspicion, a possible GI metastasis from malignant melanoma. Most patients with upper GI metastases from melanoma are asymptomatic, but when symptoms are present, chronic anemia or acute upper GI bleeding is the most common manifestation (1, 2). In some reports, macroscopic appearances of gastric lesions