Diagnosis and treatment of postoperative chyle leakage via percutaneous transabdominal catheterization of the cisterna chyli: a preliminary study

BACKGROUND AND AIMS: The liver is frequently involved in amyloidosis but the significance of hepatic amyloid has not been systematically studied. We have previously developed scintigraphy with 123I serum amyloid P component (123I-SAP) to identify and monitor amyloid deposits quantitatively in vivo and we report here our findings in hepatic amyloidosis. METHODS: Between 1988 and 1995, 805 patients with clinically suspected or biopsy proven systemic amyloidosis were evaluated. One hundred and thirty eight patients had AA amyloidosis, 180 had AL amyloidosis, 99 had hereditary amyloid syndromes, and 67 had dialysis related (beta 2 microglobulin) amyloid. One hundred and ninety two patients with amyloidosis were followed for six months to eight years. RESULTS: Hepatic amyloid was found in 98/180 (54%) AL and 25/138 (18%) AA patients but in only 1/53 patients with familial transthyretin amyloid polyneuropathy and in none with dialysis related amyloidosis. There was complete concordance between hepatic SAP scintigraphy and the presence or absence of parenchymal amyloid deposits on liver histology. Amyloidosis was never confined to the liver. Mortality was rarely due to hepatic failure, although hepatic involvement with AA amyloid carried a poor prognosis. Successful therapy to reduce the supply of amyloid fibril protein precursors was followed by substantial regression of all types of amyloid. CONCLUSIONS: SAP scintigraphy is a specific and sensitive method for detecting and monitoring hepatic amyloid. Liver involvement is always associated with major amyloid in other organ systems and carries a poor prognosis in AA type. Appropriate therapy may substantially improve prognosis in many patients.     

Renal replacement therapy in multiple myeloma and systemic amyloidosis

Renal failure frequently complicates both multiple myeloma and systemic amyloidosis. Renal replacement therapy (RRT) may be poorly tolerated and its role in such patients is not clearly defined. Of fifty patients (26 males and 24 females) referred to a single centre because of renal failure associated with multiple myeloma or systemic amyloidosis 37 progressed to end-stage renal failure and 30 of these patients received RRT. Nine patients have been treated by CAPD, 13 by haemodialysis, and 8 patients have required both forms of dialysis. Overall one year and two year survival rates were 66% and 57% respectively. The median duration on RRT was 7.5 months (range 1-96 months) with a 51% one year, and a 46% two year survival rate. Of 7 patients with amyloidosis who underwent renal transplantation, 3 died within 6 months of transplantation. Undiagnosed cardiac involvement contributed to this early mortality. We conclude that renal replacement therapy is appropriate for some patients with multiple myeloma and systemic amyloidosis who develop endstage renal failure. Careful assessment and selection of patients is necessary prior to renal transplantation.     

Non-real-time computed tomography-guided percutaneous ethanol injection therapy for hepatocellular carcinoma undetectable by ultrasonography

Fibrosing cholestatic hepatitis (FCH) has recently been described after solid organ transplantation in patients with hepatitis C virus (HCV) infection. Typically, FCH is characterized by an ominous clinical course leading to progressive hepatic failure and death if liver transplantation is not performed. Two HCV-infected patients underwent cadaveric renal transplantation for end-stage renal disease resulting from membranous nephropathy and diabetic nephropathy. The time intervals between transplantation and the biopsy diagnosis of FCH for the two patients were 7 months and 10 years. Both patients presented with jaundice, hyperbilirubinemia, and mild-to-moderate elevations in serum aspartate aminotransferase. One patient was also found to have type II mixed cryoglobulinemia. Interferon-alpha therapy was begun after a diagnosis of FCH was established by liver biopsy. Liver test abnormalities normalized rapidly. When cholestatic hepatic deterioration develops in an HCV-infected organ allograft recipient, the diagnosis of FCH should be considered and a liver biopsy performed. Our observations indicate that FCH can respond to antiviral therapy.     

Localizations and consequences

The symptoms of amyloidosis depend on the type of precursor, the amount of deposits and their location. In systemic amyloidosis almost every organ may be involved. Cardiac involvement is severe, especially in AL amyloidosis, responsible for restrictive cardiomyopathy with right ventricular failure, leading rapidly to death. Renal amyloid deposition causes nephrotic syndrome with hypertension and renal failure. Neurological complications include peripheral neuropathy with dysautonomia cerebral involvement (dementia, cerebral haemorrhages). Arterial deposits are common in systemic senile amyloidosis, and may cause ischaemia. Osteo-articular damage is mainly seen in patients on long-term haemodialysis. Liver enlargement is often the only manifestation of hepatic amyloidosis. Digestive tract involvement includes macroglossia deposits in salivary glands and disturbances in gastrointestinal motility. Pulmonary amyloidosis causes nodular or interstitial infiltrates. Cutaneous lesions are various. Localized amyloidoses include goiter, breast and vesical involvement which can be difficult to differentiate from neoplasm, as well as ocular amyloidosis mimicking posterior uveitis.     

Case report: acute renal vein thrombosis in patients with spinal cord injury and secondary amyloidosis

Chronic spinal cord injury, when complicated by chronic suppurative infections, has replaced chronic tuberculosis as a leading cause of secondary amyloidosis. Renal involvement with secondary amyloidosis is characterized by the presence of nephrotic range proteinuria and an increased incidence of renal vein thrombosis. Two cases of acute renal vein thrombosis associated with secondary amyloidosis in patients with spinal cord injury are presented. In both cases, a past history of extensive decubitus ulcerations and urinary tract infections preceded the development of nephrotic range proteinuria. In case 1, nonoliguric acute renal failure occurred after the development of acute bilateral renal vein thrombosis. The patient declined dialytic therapy and expired with uremia. In case 2, worsening renal function and increased proteinuria resulted after the development of acute unilateral renal vein thrombosis. These cases include the clinical and anatomic findings of acute renal vein thrombosis that occur as a complication of secondary amyloidosis. Acute renal vein thrombosis should be considered whenever an acute change in renal function or increase in proteinuria is noted in this setting.     

Amyloidosis in rheumatoid arthritis. A study of 48 histologically confirmed cases

In a group of 269 patients with rheumatoid arthritis histological examination demonstrated amyloidosis in 48 cases, viz. in 7 post mortem cases, in 28 rectal biopsies, in 12 renal biopsies and in one liver biopsy. Examination for amyloidosis was carried out in all patients who had proteinuria, otherwise in non-selected patients with definite rheumatoid arthritis. Even through rectal biopsy is a valuable screening method, it should not be overestimated, because in 12 patients with renal biopsy positive for amyloid, the foregoing rectal biopsies had been negative. According to our experience the most valuable method for diagnosis of amyloidosis in rheumatoid patients is renal biopsy, whereas synovial biopsy is the least conclusive. This paper, according to our knowledge, is the first report on observations of a regression of the inflammatory activity of rheumatoid arthritis and nephrotic syndrome as well as a complete morphological regression of amyloidosis.     

Myopathy in primary systemic amyloidosis

OBJECTIVE: To define the natural history of primary systemic amyloidosis when muscle involvement is prominent at presentation. METHODS: A retrospective review was carried out of all patients seen at the tertiary referral practice of the Mayo Clinic between 1 January 1960 and 31 December 1994. All patients with primary systemic amyloidosis and proof of amyloid deposits by muscle biopsy were included for analysis. No patients were lost to follow up. RESULTS: Twelve patients were identified with amyloidosis in muscle. Muscle involvement was the most prominent symptom in patients who had widespread visceral involvement, which included the heart, peripheral nerve, and tongue. Of the 12, three had skeletal muscle pseudohypertrophy. All patients had a demonstrable dysproteinaemia by the finding of free light chain in the serum or urine, a discrete monoclonal peak on serum or urine protein electrophoresis, or a monoclonal population of plasma cells in the bone marrow. Measurement of creatine kinase was not a useful test. Of eight patients treated with chemotherapy based on alkylating agents, three responded. The median survival for the entire group was 12 months. CONCLUSIONS: The finding of a monoclonal protein in a patient with muscle weakness is an important clue to the diagnosis of primary systemic amyloidosis. Most patients have visceral involvement outside the musculoskeletal system. A subset of patients seems to respond to systemic chemotherapy. The overall survival, however, remains poor, with most patients dying of cardiac failure. Immunoelectrophoresis of serum and urine should be a routine diagnostic test during the evaluation of myopathy of unknown cause.     

Hepatic failure in a case of multiple myeloma-associated amyloidosis (kappa-AL)

We report a case of kappa-AL amyloidosis which rapidly developed hepatic failure in a 79-year-old Japanese female who was admitted to our hospital because of abdominal distension and loss of appetite. Laboratory examination revealed a marked deterioration of liver function with cholestasis and monoclonal gammapathy. At the time that the diagnosis of IgG-kappa type multiple myeloma was made, jaundice was advanced, with continuous gastrointestinal bleeding. The patient died of hepatic failure 2 weeks after admission. Needle biopsy of the liver revealed a diffuse, massive deposition of amyloid protein.     

Dose-intensive melphalan with blood stem-cell support for the treatment of AL (amyloid light-chain) amyloidosis: survival and responses in 25 patients

AL (amyloid light-chain) amyloidosis is an uncommon plasma cell disorder in which depositions of amyloid light-chain protein cause progressive organ failure and death in a median of 13 months. Autologous stem-cell transplantation is effective therapy for multiple myeloma and therefore, we evaluated its efficacy for AL amyloidosis. Patients with adequate cardiac, pulmonary, and renal function had stem cells mobilized with granulocyte-colony stimulating factor and were treated with dose-intensive intravenous melphalan (200 mg/m2). Response to therapy was determined by survival and improvement of performance status, complete response or persistence of the clonal plasma cell disorder, and change in the function of organs involved with amyloid at baseline. We enrolled 25 patients with a median age of 48 years (range, 29-60), all of whom had biopsy-proven amyloidosis with clonal plasma cell disorders. Twenty-two (88%) were Southwest Oncology Group performance status 1 or 2 within a year of diagnosis, and 16 (64%) had received no prior therapy. Predominant amyloid-related organ involvement was cardiac (n = 8), renal (n = 7), hepatic (n = 6), neuropathic (n = 3), and lymphatic (n = 1). Fifteen patients had one or two organ systems involved, whereas 10 had three or more involved. With a median follow-up of 24 months (12-38), 17 of 25 patients (68%) are alive, and the median survival has not been reached. Thirteen of 21 patients (62%) evaluated 3 months posttransplant had complete responses of their clonal plasma cell disorders. Currently, two thirds of the surviving patients (11 of 17) have experienced improvements of amyloid-related organ involvement in all systems, whereas 4 of 17 have stable disease. The improvement in the median performance status of the 17 survivors at follow-up (0 [range, 0-3]) is statistically significant versus baseline (2 [range, 1-3]; P < . 01). Significant negative prognostic factors with respect to overall survival include amyloid involvement of more than two major organ systems and predominant cardiac involvement. Three patients have experienced relapses of the clonal plasma cell disorder at 12 and 24 months. Dose-intensive therapy should currently be considered as the preferred therapy for patients with AL amyloidosis who meet functional criteria for autologous transplantation.     

Effects of angiotensin II-receptor blockade with losartan on insulin sensitivity, lipid profile, and endothelin in normotensive offspring of hypertensive parents

BACKGROUND: Acute liver failure (ALF) secondary to malignant infiltration of the liver is rare and is diagnosed often only after death. AIMS: To determine diagnostic factors and particular clinical patterns of illness. METHODS: Review of case notes from all patients with ALF secondary to hepatic infiltration admitted to this unit over an 18 year period (1978-1995). RESULTS: From a total of 4020 admissions, 18 patients were identified with ALF attributable to hepatic infiltration. Mean age was 40.7 years. Aetiology was non-Hodgkin's lymphoma in nine patients, Hodgkin's disease in three, infiltrative metastatic carcinoma in four, and haemophagocytosis with no precipitant cause in two cases. Prodromal symptoms were non-specific, but occurred at least two to four weeks before onset of ALF, making the presence of such symptoms of value in differential diagnosis of the cause of ALF. Clinical examination and investigations were unhelpful in distinguishing these cases from more usual causes of ALF. Usually, the clinical course was of rapid deterioration and death from multiorgan failure, and only one patient survived. Diagnosis was made during life in 15 patients. Histology showed evidence of widespread hepatocellular necrosis, with diffuse infiltration by tumour cells rather than focal cellular aggregation. CONCLUSIONS: Only with accurate histological diagnosis from liver biopsy and institution of specific therapy early in the management of such patients will the best chance of recovery be achieved. In every case of ALF with prodromal symptoms or abnormal imaging, hepatic histology should be obtained by liver biopsy as soon as possible to diagnose infiltrative hepatic disease.     

Type AA renal amyloidosis in sarcoidosis

Sarcoidosis is an uncommon cause of secondary amyloidosis. We describe in this paper the case of a 39 years old patient, with a pulmonary and hepatosplenic sarcoidosis. A nephrotic syndrome led to a renal biopsy which showed AA type amyloidosis. As no other cause of amyloidosis has been found we admitted that it was a result of sarcoidosis which was associated with the unusual inflammatory syndrome.     

Factors influencing outcome and length of stay in a stroke rehabilitation unit. Part 2. Comparison of 318 screened and 248 unscreened patients

Amyloidosis associated with Crohn's disease was found in 7 patients among 85 subjected to intestinal resection for granulomatous enterocolitis. Most of the patients had symptoms of inflammatory bowel disease of relatively short duration before the diagnosis of amyloidosis was made and were without suppurative complications. Systemic involvement was seen in 6 of the patients. One died postoperatively from renal failure, and in 2 other patients kidney transplantation was performed because of deterioration of a pre-existent renal insufficiency. Six patients were alive 6 months to 10 years after amyloidosis was diagnosed. There is great risk of rapid deterioration of kidney function postoperatively in these patients. However, our experience suggests that in some cases the progression of amyloidosis may be delayed or even brought to a halt after surgical treatment of Crohn's disease.     

Sex differences and lateral specialization of hemispheric functioning

Acute renal failure developed in nine of 78 patients who were subjected to hepatic artery ligation for nonresectable and extensive malignant tumor of the liver. Of those nine, six had hepatomas, one cholangiocarcinoma, one metastatic islet-cell carcinoma and one metastatic melanoma. Preoperative renal function as reflected in blood-urea-nitrogen and serum creatinine values was within normal limits. There were marked elevations of serum glutamic-oxalacetic transaminase and lactic dehydrogenase levels after hepatic artery ligation, an indication of massive ischemic injury of the tumor and the liver. A diagnosis of acute renal failure was established within 14 to 70 hours after hepatic artery ligation. In five patients, oliguric renal failure developed, and in four, high urinary output renal failure. In only three patients did systemic hypotension and hypovolemia precede acute renal failure. Seven of the nine patients died. Postmortem examination was done in five patients, and in only two was there evidence of renal tubular necrosis. The factors contributing to acute renal failure appear to be extensive involvement of the liver by tumor, presence of ascites and jaundice, occlusion of the portal vein and hyperuricemia. The presence of any one of the foregoing contraindicates the procedure.     

Primary systemic amyloidosis with delayed progression to multiple myeloma

BACKGROUND: Primary systemic amyloidosis (AL) and multiple myeloma both are clonal plasma cell proliferative disorders. Although 10-15% of patients with myeloma have coexisting primary amyloidosis, it is unusual for patients with primary amyloidosis to progress to myeloma at a later date. The authors describe a case series of six patients in whom such progression occurred. METHODS: A computerized search was done of the medical records of all patients seen at the Mayo Clinic between January 1, 1960 and December 31, 1994 with a diagnosis of AL. Of 1596 patients with AL, 6 patients (age range, 60-74 years; median age, 68 years) with biopsy-proven AL were reviewed in whom delayed (at least 6 months after the diagnosis of AL) progression to multiple myeloma occurred. RESULTS: At the time of the diagnosis of AL, none of the six patients had evidence of multiple myeloma. The dominant manifestation of AL was peripheral neuropathy in three patients and cutaneous AL, renal AL, and amyloid arthropathy in one patient each. The diagnosis of multiple myeloma was made 10-81 months after the diagnosis of AL, based on the demonstration of multiple osteolytic lesions (4 patients) or marked bone marrow infiltration (> or = 50%) by plasma cells (5 patients). Two patients had received chemotherapy (melphalan and prednisone) for AL. Five patients received chemotherapy (four patients) or high dose methylprednisolone (one patient) after the diagnosis of multiple myeloma. Five patients died, and the median actuarial survival after the diagnosis of multiple myeloma was 20 months. Multiple myeloma was the cause of death in four patients; one patient died of systemic amyloidosis. In 2 patients death occurred within 3 months. CONCLUSIONS: AL occasionally progresses to overt multiple myeloma. These cases usually occur in patients without significant cardiac or hepatic AL who live long enough to develop multiple myeloma.     

Liver transplantation resolves the hyperdynamic circulation in hereditary hemorrhagic telangiectasia with hepatic involvement

BACKGROUND & AIMS: Hepatic involvement in hereditary hemorrhagic telangiectasia is common but often asymptomatic. However, in some cases, the vascular lesions that involve the liver may lead to high-output cardiac failure and pulmonary hypertension that is predominant over hepatobiliary manifestations. Liver transplantation and treatment of these complications are described and discussed in this article. METHODS: Three patients with hereditary hemorrhagic telangiectasia and hepatic involvement received transplants. They had pulmonary hypertension and chronic right-sided heart failure caused by disseminated intrahepatic telangiectasias with shunts between the hepatic artery and hepatic veins or portal vein. Left-to-right intrahepatic shunt output was estimated to range between 51% and 57.5% of cardiac output. RESULTS: Hyperdynamic circulation disappeared after liver transplantation in all patients. Results of computed tomography and right-sided heart catheterization performed 6 months later were normal. Follow-up periods currently are 65, 53, and 29 months, and each patient continues to be asymptomatic. CONCLUSIONS: This report suggests that liver transplantation can be considered as an alternative and successful curative treatment that may prevent the irreversible evolution of cardiopulmonary disease.     

Autoimmune interstitial nephritis and hepatitis in polyglandular autoimmune syndrome

A 6-year-old female with polyglandular autoimmune syndrome type I, chronic active hepatitis, and renal failure is described. The renal biopsy demonstrated advanced tubulointerstitial disease with antibodies directed against tubular basement membranes. The patient's serum contained circulating antibodies directed against both renal and hepatic parenchyma. Renal disease culminating in renal failure and anti-tubular basement membrane disease have not been previously reported in association with polyglandular autoimmune disease. We describe for the first time a patient with polyglandular autoimmune syndrome, chronic active hepatitis, circulating antibodies directed against both renal and hepatic parenchyma, and primary tubulointerstitial disease culminating in renal failure.     

Dialysis in the treatment of renal failure in patients with liver disease

The value and effects of treating renal failure by dialysis are analyzed in a series of 84 patients with various types of liver disease. Although none of the 25 patients with cirrhosis survived, six of 50 with fulminant hepatic failure recovered completely as did seven of nine patients with renal failure secondary to extrahepatic biliary tract obstruction or with liver and renal damage following episodes of severe hypotension. Dialysis was required for seven weeks before diuresis occurred in one patient in the latter group. Both peritoneal and hemodialysis satisfactorily controlled plasma urea and creatinine levels, except in patients with fulminant hepatic failure in whom this was only achieved by hemodialysis. Complications of dialysis were most common in patients with cirrhosis and fulminant hepatic failure and included hypotension, gastrointestinal bleeding, and intraperitoneal sepsis. Overall, the results show that dialysis is only worth attempting in those patients in whom recovery of the underlying liver lesion is possible, and even then treatment for prolonged periods may be necessary.     

Hepatitis C--associated glomerular disease in liver transplant recipients

Hepatitis C virus (HCV) infection may be associated with extrahepatic illness including renal disease. We investigated the clinical and virological characteristics of three patients who developed a mesangial proliferative and sclerosing glomerulopathy alone or in association with membranoproliferative glomerulonephritis after liver transplantation for end-stage liver disease secondary to HCV infection. Using polymerase chain reaction technology and the IgM RIBA assay, viral load, genotype and IgM antibody response to HCV in the setting of glomerulonephritis was evaluated. Within 1 year of transplantation, the patients showed decreased renal function, proteinuria and recurrent hepatitis C liver disease. Likewise, HCV viral load increased following transplantation, whereas the viral genotypes remained unchanged. Although the first patient presented with classic type II cryoglobulinemia in association with glomerulonephritis, the second patient developed an IgM directed specifically against the hepatitis C core antigen. The third patient developed a low-titered IgM directed against the hepatitis C core antigen with rheumatoid factor activity but without cryoglobulinemia. All of the patients show IgM in glomerular capillary walls by biopsy. One patient has shown a clinical response to interferon (IFN) alfa-2b therapy without evidence of hepatic allograft rejection. The second and third patients have not responded to IFN or developed hepatic rejection. This study suggests that HCV-associated glomerulonephritis may complicate liver transplantation in conjunction with the production of increased amounts of IgM of variable specificity. The posttransplant setting may provide a unique situation in which to investigate the specific requirements for the onset of renal disease.     

Light chain deposition disease as a cause of renal failure

The objective of the paper is to draw attention to a rare cause of rapidly progressing renal failure which developed in the course of four months as a result of light chain deposition disease. The authors submit two case-histories of the disease assessed by renal biopsy after previous clinical and laboratory suspicion of monoclonal gammapathy. In one patient in the sternal punctate plasmacytoma was diagnosed and in the second case it was not possible to detect any type of monoclonal gammapathy or another possible cause of disease. Renal failure was in both cases irreversible and both patients were enlisted in regular haemodialyzation treatment.     

Generalised amyloidosis in two Siamese cats: spontaneous liver haemorrhage and chronic renal failure

Two cases are reported, illustrating the antemortem diagnosis of systemic amyloidosis in Siamese cats. A cat presenting with inappetence and depression was diagnosed as having systemic amyloidosis with spontaneous haemorrhage from the liver. In another cat from the same breeding cattery, chronic renal failure due to systemic amyloidosis was an incidental finding. Little treatment was possible in either case and both were later euthanased. The two cats had similar renal and hepatic pathology but different signs of disease.