Metastatic cholangiocarcinoma with an occult primary.
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Biomedical subjects
Publications and source records attributed to C L Davis.
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The use of allograft biopsies to guide treatment after solid organ transplantation is a valuable tool in the detection and treatment of rejection. Prior development and use of the cystoscopically guided pancreatic allograft biopsy have allowed for more accurate and timely diagnosis of pancreatic allograft dysfunction, possibly contributing to our 1-year pancreas graft, renal allograft and patient survival rates of 87.1%, 88.5% and 96.8%, respectively. We reviewed our experience, examining efficacy and complication rates of pancreas and kidney biopsies in 31 cadaveric pancreas or combined kidney and pancreas transplants performed between June 1990 and February 1992 with at least 1 year of followup. There were 94 pancreas, 54 kidney and 53 duodenal mucosal biopsies in 29 evaluable patients. This biopsy technique uses a 24.5F side-viewing nephroscope to view the cystoduodenostomy, with the duodenum acting as a portal for biopsy needles into the pancreas. Pancreatic tissue is obtained with either an 18 gauge, 500 mm. Menghini aspiration/core needle or an 18 gauge, 500 mm. Roth core needle. Percutaneous renal allograft biopsies are performed independently or simultaneously with the pancreas biopsies using a 16 gauge spring loaded needle. Pancreas biopsies were prompted by clinical indications of rejection (decreased urinary amylase, increased serum amylase or increased serum creatinine) or by protocol (10, 21 and 40 days postoperatively). Among the biopsies 30% were required by protocol, of which 10 (36%) revealed abnormal pathological findings and 5 (18%) showed evidence of occult cellular rejection. Renal biopsies demonstrated rejection in 69% of the cases. Of simultaneous pancreas/kidney biopsies 33% revealed concomitant rejection. A total of 88 Menghini needles with 170 passes was used in 73 biopsy attempts, yielding 126 tissue cores with a 16% complication rate. A total of 41 Roth needles was used with 73 passes in 34 biopsy attempts, yielding 55 tissue cores with a complication rate of 21%. Complications included self-limited bleeding from the biopsy site in 13% of the cases, bleeding requiring clot evacuation and fulguration in 1% and asymptomatic hyperamylasemia in 12%. Renal biopsy complications included 1 arteriovenous fistula (2%). We conclude that ultrasound and cystoscopically guided pancreatic allograft biopsy and percutaneous renal allograft biopsies are safe and essential methods of obtaining tissue for histological diagnosis without serious sequelae. The Menghini and Roth needles in cystoscopically guided pancreatic allograft biopsy have similar yield and complication rates in obtaining pancreatic tissue, although they require different performance techniques. In some cases both needles are necessary and are complementary in obtaining adequate tissue.(ABSTRACT TRUNCATED AT 400 WORDS)
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The ability of prebiopsy coagulation assays to predict mild postbiopsy bleeding was evaluated in renal transplant patients undergoing renal allograft biopsy (N = 120). The coagulation assays studied included the bleeding time, prothrombin time, partial thromboplastin time, platelet count, and thromboelastograph (TEG). Coagulation results were defined as abnormal if they fell outside the established normal reference range. Bleeding was defined as a drop in the hematocrit equal to or more than 4 points 6 h after the procedure or ultrasound evidence of a new perirenal hematoma. Overall, 21% of patients showed evidence of mild bleeding. Of those who bled, 78% had normal results on all coagulation tests, indicating that most mild bleeding was not associated with coagulation abnormalities. Of the assays tested, only abnormal TEG:angle (P < 0.01) and TEG:k (P < 0.04) values were associated with an increased risk of bleeding. Bleeding times were not predictive of an increased risk of postbiopsy bleeding; five patients had abnormal bleeding times ranging from 10 to 20 min of whom only one bled. All prothrombin time, partial thromboplastin time, and platelet count abnormalities were mild (e.g., no prothrombin times longer than 15 s, no platelet counts below 129,000/microL); none of these assays predicted postbiopsy bleeding. Other clinical characteristics, including patient age, sex, serum creatinine, blood pressure (if less than 160/90 mm Hg), number of biopsy passes, or renal pathology, did not appear to influence bleeding after biopsy. It was concluded that most bleeding after transplant renal biopsy was not associated with coagulation abnormalities and that the TEG was the best assay for detecting mild coagulation abnormalities associated with an increased risk of bleeding.
Epstein Barr virus (EBV) infection has been associated with the post-transplant lymphoproliferative disorder (PTLD) in up to 8% of transplant recipients. Primary EBV infection and the use of antilymphocyte preparations appear to increase the incidence of PTLD. Experimental evidence suggests that the antiviral prophylaxis used by many transplant programs may influence the development of this post-transplant complication. In order to investigate the influence of antiviral prophylaxis (intravenous ganciclovir followed by high-dose oral acyclovir) on the development of PTLD in kidney-pancreas and liver allograft recipients from the University of Washington Medical Center, records were reviewed for pretransplant EBV status, antilymphocyte preparation use and for histologic documentation of PTLD. Two of 83 kidney-pancreas recipients (1 EBV-seronegative, 1 EBV-seropositive) and 1 of 123 liver recipients (EBV-seropositive) has developed PTLD. Six of 83 kidney-pancreas patients were EBV-seronegative prior to transplantation and 4 of these patients received at least two courses of an antilymphocyte preparation. Thirty-eight (49%) of the 77 EBV-seropositive kidney-pancreas recipients received at least two courses of an antilymphocyte globulin without the development of PTLD. Both the EBV-seronegative kidney-pancreas and the liver recipient who developed PTLD had received multiple courses of antilymphocyte globulins. One EBV-seropositive kidney-pancreas recipient had only received one course of OKT3 1 year prior to the development of PTLD. The incidence of PTLD reported here in patients receiving intravenous ganciclovir followed by high-dose oral acyclovir antiviral prophylaxis is lower than previously recorded when consideration is given for patient's EBV status and the use of antilymphocyte preparations.
Hepatitis B infection can add significantly to the morbidity and mortality of transplantation. Patients with hepatitis B can have severe recurrent disease following liver transplantation. Reactivation of occult disease can occur during chemotherapy or immunosuppression. Hepatitis B also can be acquired at the time of transplantation. Intensive study of transplant patients with hepatitis B has led to a new understanding of the immunobiology of hepatitis B virus.
Though many of the treatment strategies used in palliative care have never been subjected to clinical trial, it has been argued that advances in palliative care have outstripped those in many other specialties. This article is not a comprehensive review of therapeutic options, nor even of recent advances in this topic, but concentrates on the latest developments and controversies in the pharmacological treatment of four frequent and important symptoms: neuropathic pain, anorexia and cachexia, intestinal obstruction, and breathlessness. It is difficult to perform blinded, randomised trials in patients with advanced disease and poor performance status, yet it is these patients who may gain most from the adoption of new well evaluated treatment strategies.
We compared postoperative mortality and morbidity rates in the Veterans Health Administration (VA) to those in nonfederal hospitals, using multivariate analysis to adjust for the patient characteristics of age, diagnosis, comorbidity, and severity of illness. We used a total of 544,000 patient discharge records (330,000 nonfederal and 214,000 VA) from 1987 through 1988 and compared 118 surgical procedures or procedure groups composed of 314 individual surgical procedures. We found no significant differences in postoperative mortality rates between the VA and nonfederal hospital systems for 110 of 118 surgical procedures or procedure groups. Endarterectomy, cervical esophagostomy, and esophageal anastomosis or esophagocolostomy showed significantly lower postoperative mortality in the VA hospitals compared to nonfederal hospitals (P = 0.05). VA postoperative mortality rates that were higher than those in nonfederal hospitals and could not be entirely explained by adjusting for patient characteristics were found for suture of ulcer, cholecystostomy, colon surgery, small intestine surgery, and reopening of recent thoracotomy site (P = 0.05). Respiratory, gastrointestinal, and urinary postoperative morbidity were generally lower in the VA hospitals than in nonfederal hospitals (P = 0.05). Infections were generally higher in the VA hospitals than in nonfederal hospitals. Pulmonary embolism, deep venous thrombosis, shock due to surgery or anesthesia, mediastinitis, hemorrhage, cardiac, and central nervous system morbidity showed no significant differences. These data demonstrate that VA postoperative mortality and morbidity in 118 surgical procedures or procedure groups is comparable to those in nonfederal hospitals.
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Hepatitis C virus (HCV) is the most frequent cause of liver disease in dialysis and renal transplant recipients. Approximately 20% to 30% of the dialysis population is infected with HCV. HCV is also recognized as a cause of membranoproliferative and membranous glomerulonephritis. Enzyme immunoassay or recombinant immunoblot assay identify antibodies to multiple HCV antigens and are useful in the diagnosis of HCV infection, including infections in dialysis patients. However, after transplantation, HCV RNA identification by polymerase chain reaction is often required to detect the infection. The natural history of HCV infection using the new viral markers remains to be defined in patients treated for end-stage renal disease.
Arteriovenous fistulae (AVF) occur after percutaneous renal biopsy in up to 18% of patients. Fistulae may remain asymptomatic or lead to hematuria, hypertension, and/or renal insufficiency. The identification of an AVF has traditionally been made with angiography; however, ultrasonography, which is less invasive and nonnephrotoxic, has become a valuable tool in the localization of a postbiopsy fistula. Most postbiopsy AVF are asymptomatic and close spontaneously. Conversely, AVF may enlarge and become symptomatic, requiring embolization to reverse or prevent complications. A case of renal insufficiency in a renal transplant recipient due to a postbiopsy AVF is presented. Spontaneous closure of the AVF resulted in the resolution of renal insufficiency. One must suspect an AVF when renal insufficiency occurs in an allograft after biopsy. Further study is needed to identify ultrasound characteristics that will predict the natural history of postbiopsy AVF.
In summary, our current understanding of the therapeutics of dyspnoea is inadequate and leaves plenty of room for improvement. Rationalization of the management of this symptom has the potential to improve the quality of life of countless patients with both malignant and non-malignant disease. To date, research studies addressing this issue are sparse. Those that have been conducted are incomplete in that almost all have assessed only the effect of single dose interventions in normal volunteers or patients with COPD. There is no information on either long term dosing with these drugs or their use in patients with cancer related breathlessness. It is possible that other pharmacological agents that have never been used for this indication may have therapeutic potential. The pharmacological treatment of breathlessness deserves further investigation, and clinical studies should be conducted in parallel with appropriate laboratory studies. Drug therapy is, however, but one aspect of the overall management of any symptom, and a thorough assessment of the role of non-drug interventions for dyspnoea is also essential. Well designed multicentre studies are urgently required to evaluate the symptomatic treatment of breathlessness, but such studies must be preceded by the development of valid and sensitive patient rated tools to assess this distressing and common symptom.
Peripheral blood mononuclear cells from 13 patients with acute leukaemia were used to establish long-term interleukin-2-dependent cytotoxic T lymphocytes. Cells were grown in RPMI medium containing interleukin-2 (IL-2, 100 U/ml) and 2.5% conditioned medium prepared by activating normal lymphocytes with phytohaemagglutinin. Proliferation of IL-2-dependent CD3-positive lymphocytes was seen in 1 of 2 acute lymphocytic leukaemia cases (ALL), 1 of 4 acute myelogenous leukaemia cases (AML) (M1) and 8 of 8 more differentiated AML. In 2 cases with detectable leukaemic cell markers (1 ALL and 1 AML) passageable cells were developed, that expressed normal T cell phenotypes (namely CD3, CD4 and CD8) at the expense of leukaemic cells. In 1 of 2 cases, long-term IL-2-cultured cells showed specific cytotoxic activity against autologous leukemic cells. The percentage killing against autologous and two allogeneic target cell lines at a 50/1 effector/target (E/T) ratio was 42%, 9% and 19% respectively. Similarly the cytotoxic activity of IL-2 activated from 4 different individuals against conventional tumour targets K562 and Daudi at a ratio of 50/1 was 29%-68% (median = 55%) and 34%-78% (median = 61%) respectively. It was also found that this killing potential of the activated cells was maintained for as long as culture was continued (median 23 days, range 17-75 days). The mechanism(s) of T cell proliferation at the expense of leukaemic blast cells in the case of a minority of leukaemic patients and the possible clinical therapeutic potential of these cells following in vitro IL-2 activation deserve further investigation.
Recurrent amyloidosis is an uncommon but well-documented event in up to 26% of renal allograft recipients transplanted for amyloid renal disease. Both primary and secondary amyloidoses recur. De novo primary and secondary amyloid have not been previously reported. We report the first occurrence of de novo secondary amyloid in a renal allograft recipient. The cause of the secondary amyloidosis is unproven, but possible etiologies include inflammation secondary to occult hepatitis, rheumatoid arthritis, or chronic rejection. Colchicine therapy has not resulted in decreased proteinuria or improved renal function.
VCAM-1, a leukocyte adhesion molecule expressed by cytokine-activated endothelial cells in culture, may mediate mononuclear leukocyte infiltration in vessels and interstitium in solid organ allograft rejection. Using the avidin-biotin immunoperoxidase technique and an affinity-purified rabbit polyclonal antisera to recombinant human VCAM (rVCAM Ab) which works in methyl Carnoy's fixed tissues, we studied the expression of this molecule in biopsies of transplanted kidneys (N = 34) with and without features of rejection and allograft nephrectomies (N = 17) as well as nontransplanted control tissues (N = 26). The rVCAM Ab showed a population of reactive endothelial cells limited to sites of prominent subendothelial leukocytic cell infiltration in arteries and veins, and occasional peritubular capillaries (PTC) in rejecting allografts. Endothelial expression of VCAM was rarely identified in biopsies showing interstitial rejection only or cyclosporine toxicity, usually in PTC, and was only rarely encountered in nontransplanted control tissues. Apparent de novo expression of VCAM-1 by arterial smooth muscle cells and mesangial cells was present in cases of severe rejection. In addition, a population of cells (DC) with dendritic morphology was identified by rVCAM Ab within sites of lymphoid cell aggregation in rejecting allografts. Further evidence that these cells represent true DC was obtained by identification of VCAM-1 positive, morphologically similar cells in both germinal centers and interfollicular areas of all seven reactive lymph nodes tested; and by similar staining of these cells in the allografts and lymph nodes by antibodies to nerve growth factor receptor and the complement receptor CR1, previously shown to recognize DC. DCs were generally not seen in uninflamed normal control organs or portions of allografts uninvolved by lymphoid aggregates. Enhanced tubular epithelial cell expression of VCAM-1 was also present in rejecting allografts. All staining could be abolished by absorption of the antisera with VCAM-1 transfected, but not ICAM-1 or ELAM-1 transfected, CHO cells. In situ hybridization studies utilizing a cDNA probe to human VCAM-1 demonstrated mRNA production by glomerular, tubular and vascular cells corresponding to sites where the protein was immunohistochemically localized.(ABSTRACT TRUNCATED AT 400 WORDS)