Chronic viral hepatitis in renal transplant recipients with allografts functioning for more than 20 years.

BACKGROUND: The impact of infection with hepatotropic viruses (hepatitis B virus [HBV] and hepatitis C virus [HCV]) on morbidity and mortality, and allograft function in renal transplant recipients with allografts functioning for >20 years is not known. METHODS AND RESULTS: Seventy-nine of 511 renal transplants performed at the Cleveland Clinic Foundation from January 1963 to January 1978 are known to have functioned for at least 20 years (level 5A). Fifty-four of these patients had hepatitis testing updated after their 19th year of transplantation. Fifteen patients had evidence of ongoing viral infection: persistent hepatitis B surface antigen in three (6%), HCV antibody (enzyme-linked immunosorbent assay II supplemented by recombinant immunoblot assay) in 11 (20%), and both viruses in one (2%). Of the 10 surviving patients, 8 were tested further for viral replication. HCV RNA (polymerase chain reaction; Amplicore) was positive in 6/7 (86%), and HBV DNA (hybridization) was positive in 1/2 (50%). An elevated alanine aminotransferase (>35 U/L) was present in all hepatitis patients, alpha-fetoprotein >10 ng/ml in 2/8 (25%), and cryoglobulins >50 microg/ml in 3/6 (50%) infected with HCV. No hepatocellular carcinoma was detected by hepatic ultrasound. In patients with chronic viral hepatitis, probable cirrhosis developed in 20% (3/15) compared to one patient in the group without hepatitis, but there was no mortality from liver failure in either group. Diabetes mellitus was significantly more common in those with than without hepatitis (11/15 vs. 10/39; P=0.002), but severe infection was not (9/15 vs. 15/39). Five hepatitis patients (33%) have died of non-hepatic causes (one from meningitis, one from unknown cause, and three from coronary heart disease [CHD] vs. only two individuals without hepatitis [5%]; P= 0.014). Although the more frequent occurrence of CHD among those with hepatitis was not significant (7/15 vs. 8/39; P=0.09), CHD as a cause of death in those with HCV was significantly increased (P=0.03). CONCLUSIONS: Twenty-year renal transplant recipients infected with hepatotropic viruses (HBV and HCV) have a high rate of active viral replication (88%), a greater frequency of diabetes (P=0.01), and a higher overall mortality (P=0.014).

The fate of renal allografts functioning for a minimum of 20 years (level 5A)--indefinite success or beginning of the end? A proposed classification of long-term allograft survivals.

Fifty-five renal allografts (44 from living-related and 11 from cadaver donors) that have functioned for at least 20 years (mean 22.9 +/- 2.3, range 20.1 to 30.7 years) were evaluated in three groups based on renal function: group I (n = 26), with a GFR of > or = 60 ml/min/1.73 m2 or serum creatinine < or = 1.4 mg/dl and no proteinuria; group II (n = 9), with a GFR of > or = 60 ml/min/1.73 m2 or serum creatinine < or = 1.4 mg/dl but > 150 mg proteinuria/24 hr; and group III (n = 20), with a GFR < 60 ml/min/1.73 m2 and/or serum creatinine > 1.4 mg/dL with or without proteinuria. Allograft factors, including acute rejection (AR) in 62% (34/55) and delayed function (DF) in 55% (6/11) of the cadaver grafts, did not preclude 20-year success and the prospect of continued survival since they were not significantly more frequent in group I, II, or III. However, AR was confined to a limited period within the first three months posttransplant in 18/18 recipients in groups I and II but only in 7/16 of group III (P = 0.0002). In groups I and II AR was treated with IVMP in 14/18 cases and only 6/16 in group III (P = 0.035). Donor age < or = 50 years and recipient age < or = 40 years each occurred in 87% (48/55) of these transplants. One- or two-HLA haplotype matching was present in 98% (43/44) of living related transplants. Major risks to the recipient were coronary artery disease (11 cases and 3 deaths), malignancy (18 cases and 1 death), and severe infection and hepatitis (35 cases and 3 deaths, 2 of whom also had coronary artery disease). Hypertension occurred in 25 recipients and diabetes mellitus in 12. Potential open-end success was compromised by renal dysfunction in groups II and III, but appeared possible in 12 of the 26 patients in group I. There is no apparent "safe-haven" point of time for immunosuppressed renal allograft recipients, who remain at increased risk for eventual renal allograft dysfunction, as well as cardiovascular, neoplastic, infectious, and metabolic diseases. In order to clarify and standardize the words "long-term," a simple classification of long-term allograft survivals is proposed.

Changing demographics in renal transplant recipients: the 30 year Cleveland Clinic experience.

While it does appear that the most recent era of transplantation has not resulted in significant improvement in long-term allograft function, this appears to be due, at least in part, to the transplantation of increasing numbers of high-risk patients. It is noted that the improved results accomplished over prior eras of transplantation have been maintained despite the inclusion of these high-risk patients. Patients currently undergoing transplantation are more likely to be older, diabetic, obese or African American. All of these subgroups have poorer patient survival in the most recent transplant era and thus, death with a functioning graft has become a significant contributor to graft loss. Recipients were more likely to receive kidneys from cadaveric donors in the most recent era and within the live-donor groups, sibling donation has decreased. Hopefully, the recent trend of increased live-donor transplants (especially living, unrelated transplants) will continue. Cadaveric recipients were at higher risk for posttransplant ATN which, for the first time in the current era, had a significant adverse impact on graft survival. Long-term survival appeared to be associated with particular characteristics (optimal age at transplantation, optimal donor age, live donor, etc.), and can be achieved despite known risk factors, such as rejection or delayed graft function.

Perioperative management of 63 patients with pheochromocytoma.

During a 10-year period, 60 patients with confirmed diagnoses of pheochromocytoma underwent a total of 63 surgical procedure. To control extreme blood pressure elevations, 6 patients received phenoxybenzamine preoperatively and 28 patients received prazosin. The remaining 29 patients received neither drug. Intravenous sodium nitroprusside and nitroglycerin, alone or in combination, were used in all but 10 patients to control intraoperative hypertensive episodes. One patient died after surgery due to pre-existing intracranial malignant tumor. All other patients were discharged from the hospital with no clinical evidence of stroke or myocardial infarction. We conclude that pheochromocytoma patients can undergo successful surgery without preoperative profound and long-lasting alpha adrenergic blockade.

Outcome of renal transplantation in patients with a functioning graft for 20 years or more.

In the present study long-term morbidity, quality of life and over-all rehabilitation were assessed in 14 patients with a functioning renal allograft for 20 years or longer. Followup ranged from 20 to 27 years (mean 22.5 years). All patients enjoyed excellent and stable renal function, and the mean serum creatinine level at 20 years was 1.3 mg. per dl. Complications related to long-term immunosuppressive therapy comprised infection in 8 patients (57%), malignancy in 7 (50%), cardiovascular disease in 6 (43%), cataracts in 3 (21%) and avascular necrosis of the hip in 2 (14%). Over-all quality of life was excellent in 13 patients who were able to return to work, participate in pre-illness levels of activity and enjoy sexual activity. While successful renal transplantation allows patients with end stage renal failure to resume relatively normal lives, these patients remain prone to complications resulting from long-term immunosuppressive therapy.

The role of renal autotransplantation in complex urological reconstruction.

From 1972 to 1988, 108 patients underwent renal autotransplantation for renal artery disease (67), ureteral replacement (27), or renal cell carcinoma present bilaterally or in a solitary kidney (14). The most common indication for renal autotransplantation was to allow extracorporeal repair of complex branch renal artery lesions. Of the 54 patients in this group technically satisfactory branch renal arterial reconstruction and a successful clinical outcome were achieved in 52 (96%). Renal autotransplantation is the treatment of choice in these patients and also in selected children with main renal artery disease. Renal autotransplantation provided excellent results in 25 of 27 patients (92%) who required replacement of all or a major portion of the ureter. Over-all renal function was well preserved in these patients and only 1 has experienced chronic bacteriuria. Renal autotransplantation is a useful alternative to ileal interposition in this setting. Extracorporeal partial nephrectomy and renal autotransplantation were successful in 12 of 14 patients (85%) undergoing a nephron-sparing operation for renal cell carcinoma. In situ techniques are associated with less morbidity and currently are preferred in this group.

Experience with extra-adrenal pheochromocytoma.

From 1955 to 1985, 20 patients presented with a total of 22 extra-adrenal pheochromocytomas (2 had multiple tumors and 2 had a malignant extra-adrenal pheochromocytoma). There were 13 male and 7 female patients, and the highest incidence was in the second decade. Although most patients presented with symptoms typical of pheochromocytoma, several presented with unusual features related to the anatomical location, such as mediastinal mass (chest tumor), upper airway obstruction (neck tumor) or gross hematuria (bladder tumor). In 5 of 6 patients in whom plasma catecholamine levels were fractionated epinephrine levels were elevated. The most common tumor location was the superior para-aortic region (13 patients). In 16 patients the location of tumors was established before treatment. Computerized tomography (9 patients) was the most accurate imaging study for tumor localization. A total of 19 patients underwent complete excision of all pheochromocytomas. Postoperative followup information (median interval 120 months) was available for 15 of these patients. Three patients had recurrent pheochromocytoma that was treated successfully. One patient had essential hypertension. No patient had metastatic disease. The low incidence of malignancy suggests a benign course for extra-adrenal pheochromocytoma and represents a departure from the previously reported higher incidence of malignancy with extra-adrenal pheochromocytoma.

Operative approaches to the adrenal gland.

Various adrenal disorders necessitate surgical intervention, and familiarity with adrenal pathophysiology and surgical anatomy is crucial to the success of these procedures. A number of operative approaches--anterior, posterior, flank, and thoracoabdominal--are available; the choice must be made on the basis of the patient's adrenal pathology, body habitus, and surgical history as well as the surgeon's experience and familiarity with the different options.

Posterior transthoracic approach for adrenal surgery.

We present a modification of the posterior surgical approach for adrenalectomy wherein the pleura and diaphragm are directly incised to expose the adrenal gland. This technique has been used in 20 patients undergoing adrenalectomy for hyperplasia or a small benign adenoma. In our series chest tube drainage usually was not necessary, operative morbidity was minimal and most patients were discharged from the hospital within 1 week postoperatively. The posterior surgical approach remains an excellent method to perform adrenalectomy in selected patients. The transthoracic modification described can enhance operative exposure of a high-lying adrenal gland through this incision, particularly on the right side.

The Cleveland Clinic experience with adrenal cortical carcinoma.

Between 1936 and 1987, 82 patients with adrenal cortical carcinoma were seen at our clinic. Of these patients 49 (72 per cent) have been seen during the last 25 years. A total of 40 patients (48.8 per cent) presented with a hormonally functional tumor and 42 (51.2 per cent) had a nonfunctional tumor. Forty patients (48.8 per cent) presented with localized disease, 12 (14.6 per cent) with regional disease and 30 (36.6 per cent) with distant metastases. Complete surgical removal of all gross tumor was achieved in 49 patients. Over-all 3 and 5-year patient survival rates in this series were 37.5 and 25.1 per cent, respectively. Survival was significantly improved (43.9 per cent at 5 years, p equals 0.0001) in patients with localized disease that was completely removed surgically; postoperative adjuvant therapy with op'-DDD was of no benefit in these patients. Survival in patients with metastatic disease was poor and was not improved by treatment with op'-DDD, cytotoxic chemotherapy or radiation therapy.

Stomal complications of intestinal conduit urinary diversion.

Intestinal conduits of the ileum, colon, or jejunum were used for urinary diversion in 319 patients at The Cleveland Clinic Foundation between 1970 and 1981 due to pelvic malignancy , primary bladder cancer, or benign conditions. End stomas were constructed in 65% and Turnbull loop stomas in 35%. Follow-up ranged from one to 152 months (median, 35 months). The mean number of days between appliance changes was 5.7 (range, 2-10). The overall complication rate was 8.5%. Stomal revisions were required in 5%. There were no significant differences in the mean number of days between appliance changes, type or number of complications, or rate of revision between end and loop stomas or between the various intestinal segments used for diversion. The presence or absence of previous irradiation and the indication for diversion were independent of complications. Stomas constructed from any segment of the intestinal tract in end or loop fashion yielded equivalent long-term function and complication rates. Stomal complications can be minimized and the time between appliance changes maximized by careful attention to all phases of stomal construction and care.

Conservative surgery for transitional cell carcinoma of the renal pelvis.

From 1972 to 1986, 14 patients underwent a conservative operation for transitional cell carcinoma of the renal pelvis. Most of these patients had low grade (12), noninvasive (10) tumors involving a solitary functioning kidney (12). The operations performed were open pyelotomy with tumor excision and fulguration (8 patients), partial nephrectomy (5) and percutaneous nephroscopic fulguration (1). There was 1 operative death. Of the 13 surviving patients 8 (62 per cent) remained free of transitional cell carcinoma postoperatively, while 5 (38 per cent) had recurrent disease. Six patients (46 per cent) presently are free of tumor 6 months to 5 years postoperatively. Conservative surgical techniques can provide satisfactory treatment for selected patients with renal pelvic transitional cell carcinoma when preservation of functioning renal parenchyma is necessary to avoid kidney failure.