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Biomedical subjects

R L Jenkins

Publications and source records attributed to R L Jenkins.

At least 19 recordsLinked to original sources

Major infectious complications after orthotopic liver transplantation and comparison of outcomes in patients receiving cyclosporine or FK506 as primary immunosuppression.

A retrospective cohort study was conducted to determine the incidence of major infectious complications after orthotopic liver transplantation and to compare outcomes in patients receiving either cyclosporine (CsA) or FK506 (tacrolimus) as primary immunosuppression. Of 133 transplants performed in 118 patients, 124 transplant episodes were evaluated. Cytomegalovirus (CMV) infection (INF) and disease (DIS), deep fungal infection (DFI), and intraabdominal bacterial infections (IAI) were catalogued. The overall incidences of major infectious outcomes were: CMV INF = 33%; CMV DIS = 19%; DFI = 15%; and IAI = 25%. Cox proportional hazard analysis identified donor seropositivity, OKT3 as secondary immunosuppression and initial intensive care unit (ICU) duration as risk factors for CMV INF and DIS in the overall population. Fungal colonization was the dominant risk factor associated with deep fungal infection. A choledochojejunostomy anastomosis, the number of cellular blood products transfused at the time of transplantation surgery, and prior CMV INF were independent risk factors for both fungal colonization and deep infection. The single risk factor identified for intraabdominal bacterial infections was the number of cellular blood products transfused at the time of surgery. In the Cox proportional hazards model the relative risk (RR) for each category of infection was lower in the FK506 group (CMV: RR = .87, 95% confidence interval [C.I.] = [.32-2.4]; DFI: .58 [.13-2.6]; IAI: .51 [.15-1.7]), but the effect was not statistically significant. Survival was similar in patients receiving FK506 or CsA. CMV INF and DFI were independent predictors of death for all patients. Risk factors identified for CMV INF and DIS support the findings of others. Higher intraoperative blood product requirements and complicated intraoperative or postoperative courses increase the risk for IAI or DFI. The development of effective strategies to prevent CMV and fungal infections in liver transplant recipients remains a priority for future endeavors.

Bacterial Infections

Aggressive surgical resection for cholangiocarcinoma.

OBJECTIVES: To review the spectrum of cholangiocarcinoma in patients treated by a single team of hepatobiliary surgeons over an 8-year period, to evaluate the predictors of survival, and to assess the results of an aggressive approach to surgical resection. DESIGN: Retrospective review of all clinical records of patients referred for treatment of cholangiocarcinoma, with univariate analysis of clinical and pathologic factors in relation to patient survival. SETTING: New England Deaconess Hospital, Boston, Mass. PATIENTS: Eighty-eight consecutive patients referred with the established diagnosis of cholangiocarcinoma, from December 31, 1985, to April 15, 1994. INTERVENTIONS: Seventy-five of 88 patients were treated surgically, with 59 undergoing major resection for cure. Of the 29 patients treated palliatively, 16 had operations and 13 had wire mesh stents placed nonoperatively. MAIN OUTCOME MEASURES: Morbidity, mortality, and patient survival. RESULTS: Survival correlates directly with the pathologic stage (TNM). Tumor location had no impact on survival. Patients undergoing resection survived significantly longer (median, 23.2 months) than palliated patients (median, 7.7 months; P = .0015). Nonoperative palliation resulted in better survival than surgical palliation (P = .045). Major hepatic resection was used alone in eight patients with predominating intrahepatic lesions, while 18 patients with hilar lesions underwent en bloc skeletonization in conjunction with major hepatic resection. Resection with microscopically free margins significantly improved survival. Only patients undergoing major resection enjoyed survival greater than 2 years. CONCLUSIONS: Patient survival can be significantly improved by aggressive surgical resection. Hepatic resection should be used aggressively to achieve disease-free margins to optimize survival. Hepatic resection can be performed with low morbidity and mortality. Liver transplantation should be avoided as a treatment for cholangiocarcinoma. The best palliation for unresectable disease remains debatable. We advocate nonoperative treatment with endobiliary expandable wire mesh stents for patients with unresectable disease.

Adult

Biliary tract complications after liver transplantation.

OBJECTIVE: To assess the incidence, type, and treatment of biliary complications after orthotopic liver transplantation. DESIGN: Case series. SETTING: Tertiary referral center. PATIENTS: One hundred ninety consecutive adults who underwent 220 orthotopic liver transplantations with biliary reconstruction between January 1, 1989, and December 31, 1993, with follow-up of all survivors to May 1994. MAIN OUTCOME MEASURES: Incidence, type, and treatment of biliary complications. RESULTS: Biliary complications were identified in 65 of the 190 patients who underwent biliary reconstruction (49 of 147 with choledochocholedochostomy and 16 of 43 with Roux-en-Y choledochojejunostomy). The group with complications who had choledochocholedochostomy had 32 biliary leaks (22 T-tube related), 11 strictures or obstructions, and six cases of choledocholithiasis. Twelve percent of choledochocholedochostomies were converted to choledochojejunostomies, while 26 of 49 biliary complications in patients who had choledochocholedochostomies were treated nonoperatively. Elective removal of T tubes resulted in biliary leak in 15 of 89 patients, treated nonoperatively in 12. Leaks (unrelated to scheduled removal of the tube) occurred earlier than strictures (choledochocholedochostomy, mean +/- SEM 25.6 +/- 5.8 vs 184.7 +/- 61.0 days; choledochojejunostomy, 13.4 +/- 4.4 vs 521.0 +/- 142.0 days) and were more often treated operatively (choledochocholedochostomy, 14 of 17 vs three of seven; choledochojejunostomy, four of five vs three of eight). Three deaths were associated with early biliary leaks, all in patients with preexisting multiorgan dysfunction. There was no significant difference in the incidence of biliary complications by type of reconstruction, year of transplantation, age, UNOS (United Network for Organ Sharing) status, preservation time, or indication for transplantation. CONCLUSIONS: Biliary complications are common after orthotopic liver transplantation but are rarely an isolated cause of death. Stenting of the choledochocholedochostomy or choledochojejunostomy anastomosis does not prevent strictures, and T tubes are associated with a high incidence of biliary leakage on removal. Nonoperative interventions have an increasing role in the treatment of biliary complications.

Adult

Biliary intervention by means of percutaneous puncture of the antecolic jejunal loop.

PURPOSE: To evaluate the safety and efficacy of biliary intervention performed by means of percutaneous transjejunal access. MATERIALS AND METHODS: In 28 patients with conventional antecolic Roux-en-Y choledochojejunostomy or hepaticojejunostomy loops, 41 attempts were made at direct percutaneous entry into the jejunal loop. Indications for previous surgery included sclerosing cholangitis, orthotopic liver transplantation, cholangiocarcinoma, bypass of benign iatrogenic strictures, and bypass of choledochal cyst. Roux-en-Y loops were directly accessed with single-wall, 19-gauge needles after localization by review of previous cholangiograms or computed tomographic (CT) scans and localization of surgical clips with fluoroscopy. RESULTS: The transjejunal approach was successful in 36 of 41 attempts. In 30 cases, transhepatic puncture was entirely avoided. There were four minor complications and one major complication of biliary sepsis. No procedure-related deaths occurred. CONCLUSION: This transjejunal approach is an effective and safe route for a variety of percutaneous biliary procedures in patients with biliary-enteric anastomoses.

Anastomosis, Roux-en-Y

Hepatitis C infection: a rare cause of fulminant hepatic failure.

Fulminant hepatic failure is caused by a variety of viruses, toxins, and metabolic derangements. The hepatitis C virus (HCV) causes indolent development of cirrhosis and has not been associated with fulminant hepatic failure. We report the first documented case of fulminant hepatitis C in the United States. The patient developed jaundice and stage IV encephalopathy. Initial laboratory evaluation did not reveal the etiology. The patient survived without liver transplantation. Three wk later he was found to have a positive HCV RNA and anti-HCV antibody seroconversion. He continued to improve with alpha-interferon treatment and has normal liver function and a negative HCV RNA 15 months later.

Adult

Coronary artery bypass grafting in patients with transplanted livers.

Coronary artery bypass grafting was performed on 3 patients for refractory angina pectoris 48, 5, and 40 months after orthotopic liver transplantation. At the time of the cardiac operation, all 3 patients had drug-induced moderate renal dysfunction, and 1 of the 3 exhibited mild chronic rejection of the graft. Maintenance immunosuppressive therapy was continued during the cardiac operation and the perioperative period. Stress-dose steroids and standard prophylactic antibiotics were also employed. All 3 patients tolerated the cardiac surgical procedure without hepatic decompensation, excessive bleeding, infection, impaired wound healing, and other complications related to the transplanted organ or to the immunosuppressive therapy. Early postoperative liver function test results showed mild transient deterioration. One patient experienced a brief psychotic episode and massive upper gastrointestinal bleeding. Both complications were attributed to the steroids used in immunosuppressive therapy. Follow-up ranging from 2 to 24 months after coronary artery bypass grafting revealed that the patients were active and had no cardiac symptoms or manifestations of hepatic decompensation. It appears from this limited experience that cardiac operations can be performed safely in patients who have previously undergone liver transplantation.

Aged

Liver transplantation with incidental gallbladder carcinoma in the recipient hepatectomy.

Gallbladder carcinoma (GBCA) is the most common malignancy of the biliary tract and is often found seredipitiously after cholecystectomy. We report the first two cases of incidental GBCA in the native gallbladder of two liver transplant recipients. Both patients are 2.5 years following uneventful orthotopiic liver transplantation (OLTx) with no evidence of recurrent disease. Pathology of both recipients was early and favorable. Neither patient received any further therapy. Given the incidence of GBCA and the evolution of OLTx we would anticipate this finding to be more prevalent.

Aged

The impact of intraoperative ultrasonography on surgery for liver neoplasms.

To analyze the effect of IOUS on surgical decision making, we performed a retrospective study of 45 patients who had exploratory laparotomy and IOUS for liver neoplasms. Preoperative lesion detection was compared with intraoperative findings. The effect of IOUS on the choice of surgical procedure was analyzed. Preoperative imaging detected 67% of lesions, 78% when combined with surgical inspection and palpation, and 97% were recognized by IOUS. Surgery was modified in 23 of 45 cases (51%); 19 of those 23 cases (83%) were based on IOUS findings alone. IOUS demonstrated superior lesion detection over noninvasive preoperative liver imaging, and IOUS significantly affected surgical decision making.

Adult

Assessment of the cytokine response in liver donors at the time of organ procurement and association with allograft function after orthotopic transplantation.

BACKGROUND: The cause of allograft liver dysfunction after transplantation is unresolved. We tested the hypothesis that human donor liver may be predisposed to ischemia reperfusion injury, and graft dysfunction subsequent to ongoing inflammatory processes during donor hospitalization. STUDY DESIGN: A prospective study of organ donors and transplant recipients of allograft livers from these donors was conducted. Portal venous, inferior vena caval, and superior vena caval blood samples were obtained from 16 clinical organ donors at the time of organ procurement (one to 12 days post-trauma) to characterize the hepatic cytokine and acute phase protein response, to determine whether or not this response resulted from bacterial or endotoxin translocation to the portal circulation, and to assess whether or not transplant outcome was associated with plasma levels of cytokines in the donor. RESULTS: In comparison with systemic blood samples from ten healthy persons, all 16 donors exhibited significantly (p < 0.05) elevated plasma concentrations of interleukin-6, interleukin-8, soluble p55 tumor necrosis factor receptor type I (sTNFr-I), and C-reactive protein. No concentration differences existed among portal venous, inferior vena caval, and superior vena caval blood samples for any cytokine or acute phase protein measured. Donor levels of endotoxin, TNF-alpha, soluble intercellular adhesion molecule-1 (sICAM-1), alpha 1-acid glycoprotein, alpha 1-antitrypsin, and haptoglobin were comparable with those in the healthy persons. Bacterial cultures of portal blood were negative. There was no association between the causation of donor trauma and either donor cytokine response or function and quality of the allograft liver after transplantation. Nor could an association between donor cytokine response and either early allograft function (less than 96 hours) or eventual transplant outcome in the recipients be detected. CONCLUSIONS: These results indicate that, although an ongoing inflammatory response to injury was evident in these donors at the time of organ procurement, there were no apparent adverse effects arising from these inflammatory processes on the function and quality of the donor liver after transplantation. Bacterial translocation does not seem to be a component of the pathogenesis of inflammation. Whether or not the presence of inflammation in the donor alters the metabolic responses of the allograft liver and recipient to transplant operation is unknown.

Acute-Phase Proteins

Technical and biological factors in disease-free survival after hepatic resection for colorectal cancer metastases.

Careful patient selection for hepatic resection of colorectal cancer metastases is essential to improve current poor results. Carcinoembryonic antigen level and number of metastases were significant preoperative prognostic indicators of 5-year disease-free survival in patients selected clinically for hepatic surgery. Surgical margin, weight of hepatic tissue resected, carcinoembryonic antigen level, and flow cytometry were significant postoperative prognostic indicators. Patients with a carcinoembryonic antigen level less than 200 ng/mL, 1-cm surgical margins, and less than 1,000 g of liver tissue removed had a greater than 50% estimated 5-year disease-free survival rate. If the metastases were diploid on flow cytometry, an additional survival advantage may have been gained. Inadequate surgical margins led to high rates of liver-only recurrence. Nonhepatic recurrence was unrelated to surgical margins. Intraoperative liver examination by ultrasound during primary colon cancer resection and adjuvant chemotherapy may offer earlier selection of biologically appropriate patients and improved outcome; both recommendations require clinical trials.

Adult

The high-risk liver allograft recipient. Should allocation policy consider outcome?

The Boston Center for Liver Transplantation has accumulated one of the larger series of liver allograft recipients. This review has provided an opportunity to examine recent pronouncements by Medicare regarding patient selection and survival and to question whether the current allocation scheme best utilizes a scarce supply of donor liver allografts. Patients with primary biliary cirrhosis, sclerosing cholangitis, and metabolic derangements have enjoyed excellent survival: in aggregate, 78.9% at 1 year. In contrast, patients suffering from acute hepatic failure, patients requiring life support, or patients with primary graft failure who need a second liver transplant did poorly compared with other recipient groups: 45% 1-year survival. This center's experience reflects a more realistic expectation of patient survival because it considers the high-risk recipient by diagnosis and urgency status. This study also suggests that assessment of outcome should be a component of allocation planning in the future.

Adult

Liver transplantation for primary hepatic cancer.

Although early survival following transplantation for primary hepatic cancer is excellent, previously reported high recurrence rates have generally discouraged liver replacement for this indication. Since the inception of the Boston Center for Liver Transplantation (BCLT) in 1983, 33 of 383 (8.6%) liver allograft recipients have undergone orthotopic transplantation as definitive treatment for otherwise unresectable cancer. Diagnoses included hepatocellular carcinoma (HCCA) in 24 patients (73%), and cholangiocarcinoma (CHCA) in 9 patients (27%). Actuarial survival rates for patients with hepatocellular carcinoma were 71%, 56%, and 42% at 1, 2, and 3 years, respectively. The actuarial survival rates for patients with cholangiocarcinoma were 89% at 6 months, and 56% at 1, 2, and 3 years. Of the nine patients with cholangiocarcinoma, 56% (5/9) developed recurrent disease. Although this recurrence rate is disheartening, because of the lack of other morbidity, long-term survival in these patients is comparable to patients with HCCA. In contrast, recurrent hepatocellular carcinoma developed in 25% of recipients (5/20) who survived longer than 3 months posttransplantation. Other causes of death in patients with hepatocellular carcinoma included perioperative complications, 16.6% (4/24); sepsis, 8.3% (2/24); coronary artery disease, 4.2% (1/24); and lymphoma, 4.2% (1/24). Favorable prognostic factors included: primary tumor less than 3 cm in size and absence of associated cirrhosis. These results emphasize that orthotopic liver transplantation can provide a long-term cure for approximately 50% of patients whose primary hepatic malignancy is unresectable by conventional procedures.

Adenoma, Bile Duct

Combined liver and whole pancreas procurement in donors with a replaced right hepatic artery.

Aberrant donor arterial anatomy, such as a replaced right hepatic artery, is often considered a contraindication to combined liver and whole pancreas procurement for transplantation. With the increasing interest in transplantation of the pancreas and the demand for cadaver organs, methods for simultaneous procurement despite aberrant donor anatomy are essential. We describe the surgical techniques used successfully in six instances of combined liver and whole pancreas procurement in donors with a replaced right hepatic artery and suggest that a replaced right hepatic artery should not preclude simultaneous procurement in otherwise suitable donors.

Anastomosis, Surgical

Acute hepatic failure associated with oral minocycline: a case report.

A 39-year-old woman was evaluated for possible liver transplantation due to rapidly developing hepatic failure 4 weeks after initiation of oral minocycline 100 mg twice a day for the treatment of acne. The patient developed a maculopapular rash, malaise, fever, nausea, and vomiting 2 weeks prior to admission to the hospital. On admission, her symptoms rapidly progressed to liver failure characterized by rapidly rising liver enzyme levels, worsening encephalopathy, and coagulopathy. Viral hepatitis serologies and blood cultures were all negative. After intensive supportive care for 2 weeks, the patient's condition gradually improved and she was discharged with mildly elevated liver enzyme levels and pruritus, without need of liver transplantation. Minocycline-induced hepatic injury is an idiosyncratic reaction with a sensitization period that appears to be 3-4 weeks in duration. The characteristic features include rash, fever, lymphadenopathy, and eosinophilia, as well as severe alterations in liver function. The high liver enzyme levels and the significant prolongation of the prothrombin time suggest massive hepatocellular damage. In light of the profound liver damage that occurs with this adverse reaction, care should be taken in administering minocycline to patients who have concomitant liver disease. It is recommended that patients should be instructed as to the possible signs and symptoms of toxicity and be monitored for evidence of idiosyncratic reaction or liver failure.

Acne Vulgaris

Changes in AMP deaminase activities in the hearts of diabetic rats.

AMP deaminase from normal and diabetic rat hearts was separated on cellulose phosphate and quantitated by HPLC. From soluble fractions three different AMP deaminase activities, according to KCl elution from cellulose phosphate and percent of total activity were: 170 mM (85%), 250 mM (8%) and 330 mM (7%) KCl. The AMP deaminase activity which eluted with 170 mM KCl was resolved to two distinct peaks by HPLC anionic exchange. After 4 weeks of diabetes the heart enzyme profile change to: 170 mM (10%), 250 mM (75%) and 330 mM (15%). Once purified the four activities were kinetically distinct: 170 mM KCl cytosolic, AMP Km = 1.78, stimulated by ATP, GTP, NADP and strongly inhibited by NAD; 170 mM KCl mitochondria AMP Km = 17.9, stimulated by ATP, ADP; 250 mM KCl isozyme, AMP Km = 0.66, stimulated by ADP; and 330 mM KCl isozyme, AMP Km = 0.97, inhibited by ATP, NAD(P).

AMP Deaminase

Sequential interleukin 2 and interleukin 2 receptor levels distinguish rejection from cyclosporine toxicity in liver allograft recipients.

Previous studies of renal transplant recipients have demonstrated that allograft rejection is accompanied by an increase in plasma and urinary levels of interleukin 2 and its soluble receptor before the development of clinical symptoms. After measuring interleukin 2 and interleukin 2 receptor levels in the plasma, bile, and urine of liver transplant recipients, we found that rejection is preceded by elevation of plasma and biliary levels of both substances, that cyclosporine toxicity did not affect either of these levels, and that urinary levels of the substances are unaffected in either condition. Levels of interleukin 2 and interleukin 2 receptors increased in bile earlier than in plasma, and interleukin 2 levels did not overlap among stable patients and those experiencing rejection, whereas levels of interleukin 2 receptors did. Serial measurements of interleukin 2 levels, particularly in the product of the transplanted organ, provide a reliable assessment of the immunologic status of the allograft.

Bile