Prognostic factors for survival after pancreaticoduodenectomy for malignant disease.

Forty patients underwent pancreaticoduodenectomy for malignant disease in a 25-year review of 6 Portland-area hospitals. After resection, 10 patients survived for greater than 5 years. Characteristics of survivors included a short prodrome of symptoms, minimal weight loss, tumor in the periampullary region, and female sex. Factors that did not influence survival included degree of jaundice, primary tumor size, and initial abnormal liver function studies.

Problems in diagnosis and management of desmoid tumors.

Thirty-two primary desmoid tumors occurred in 29 patients. The median patient age was 32 years, and 55% of the patients were females. An antecedent history of trauma at the tumor site was elicited from 28% of patients. Thirty-one of 32 primary tumors were completely excised at initial presentation. Five tumors were treated with adjuvant radiotherapy. The overall recurrence rate for primary and recurrent lesions was 60%. The recurrence rate in children (88%) was more than twice that found in adults (38%). A single recurrence did not significantly increase the likelihood of a subsequent recurrence. Greater than 90% of all recurrences took place within 3 years of treatment. The rate of recurrence was not clearly influenced by the status of histologic margins, although this was examined in less than half the tumors. Desmoid tumors are aggressive neoplasms that exhibit a strong propensity for local recurrence. They should be treated as low-grade malignancies with documentation of histologic margins and close clinical follow-up within the framework of a tumor registry.

The effect of prolonged aspirin therapy on experimental balloon-catheter arterial wall injury.

Indications for aspirin following percutaneous transluminal angioplasty are not well defined. Although aspirin's early antithrombotic effect is believed to be beneficial, the long-term influence of aspirin on myointimal proliferative response following balloon-catheter angioplasty is still being investigated. This study quantitates arterial wall thickening, including intimal hyperplasia, at 4 months following balloon-catheter aortic injury in New Zealand white rabbits (n = 12), comparing aspirin treatment (30 mg/kg) with controls. Aspirin was administered daily for 1 month prior and 4 months following aortic injury. Myointimal proliferation was noted in both groups. The mean area of the intima and media as well as the maximum thickness of the intima were similar (p greater than .05) in both the aspirin treatment and control groups. Cellular hyperplasia was evaluated by media smooth muscle cell counts using an ocular reticle. There was a trend toward higher cell counts with aspirin treatment, although there was no significant difference between the two groups. Prolonged aspirin therapy did not alter the degree of myointimal hyperplasia at 4 months postinjury in our model.

Repeat parathyroid operation associated with renal disease.

One hundred ten patients who had undergone operation for secondary and tertiary hyperparathyroidism have been described. Ninety patients had secondary disease and 20 patients had tertiary disease after renal transplantation. From these two groups, 18 patients had repeat operations for control of recurrent or persistent disease. The incidence of repeat operations was 14 percent. Causes were graft-dependent hyperparathyroidism, supernumerary glands in the neck or mediastinum, and incomplete identification of glands in the neck. The most important risk factor is continued long-term dialysis in functionally anephric patients. We recommend that patients with hyperparathyroidism associated with chronic renal failure undergo total parathyroidectomy with autotransplantation. If repeat operation is necessary, a reduction in glandular mass with autotransplantation is preferred. In selected patients, total parathyroidectomy can be considered because of the increased risk of aluminum bone disease.

Anatomical heterogeneity of parathyroid glands in posttransplant hyperparathyroidism.

Successful renal transplantation may be complicated by persistent hyperparathyroidism due to diffuse parathyroid hyperplasia remaining from a prolonged period of pretransplant chronic renal failure treatment. Posttransplant hyperparathyroidism is distinct from primary hyperparathyroidism, being characterized by multiple gland involvement and diffuse hyperplasia rather than a single adenoma. The gross pathologic anatomy of the parathyroid glands was assessed in 17 successful renal transplant recipients. Individual and total gland volumes were measured at the time of total parathyroidectomy and forearm reimplantation. Parathyroid hyperplasia was heterogenous in both location and gland size. Right-sided glands were enlarged more than left-sided ones. Subjects with primary tubulointerstitial disease exhibited greater hyperplasia than patients with glomerular disorders. Clinicians should be aware of the heterogeneity of the gland enlargement in patients with diffuse parathyroid hyperplasia, so that these patients are not misdiagnosed as suffering from adenomatous parathyroid disease.

Detection of bile leakage from traumatic right hepatic duct laceration with technetium-99m DISIDA cholescintigraphy.

A woman was admitted to the hospital after blunt abdominal trauma. Initial ultrasound was equivocal but suggested a localized hepatic laceration. The patient was discharged but returned three weeks later with ascites and mild pain in the right upper abdominal quadrant. Hepatobiliary imaging identified a large bile leak originating from the porta hepatis but showed no evidence of parenchymal injury. No hepatic injury was found at surgery, but a laceration of the right hepatic duct was identified. Hepatobiliary imaging is the procedure of choice in diagnosing bile leaks from the extrahepatic biliary system.

Clinical spectrum of patients with infrarenal aortic grafts and gastrointestinal bleeding.

Nineteen patients with a prosthetic infrarenal aortic graft and gastrointestinal bleeding were managed over a 7 year period. Graft-to-enteric fistula, identified in five patients, was the most common cause of bleeding. Other causes included bowel ischemia (four patients) and peptic ulcer disease (three patients). Clinical signs of infection, such as fever and leukocytosis, were common in patients with graft-to-enteric fistula and bowel ischemia. Most of these patients will benefit from a prompt evaluation and expedient operation.

Accessory cell function of the endothelial cell: its role in the cellular immune response.

We have proposed a hypothesis in which vascular endothelial cells, rather than or in addition to bone-marrow-derived cells, play an integral part in the antigen presentation event of cell-mediated immune phenomena including delayed-type hypersensitivity (DTH). Previously we have shown that a DTH ear-swelling response can be adoptively transferred in rats, using as few as 2 x 10(7) in vitro conditioned immune spleen cells. The transfer is antigen-specific, requiring the same sensitizing antigen in both the in vitro conditioning step and in the ear-test challenge. Adoptive transfer is also genetically restricted by alleles of the RT-1 region of the rat, requiring histocompatibility between immune donor cells and the naive recipient. In additional experiments, F1 to parental bone-marrow chimaeras were constructed such that the bone-marrow-derived cells and the non-bone-marrow-derived cells were of different RT-1 allotypes. When these chimaeras were used as adoptive transfer recipients, the transfer of DTH was possible only if the immune donor cells and the recipient non-bone-marrow-derived cells shared a common RT-1 haplotype, regardless of a shared haplotype with the bone-marrow-derived cells. These results point to a critical role for non-bone-marrow-derived cells (endothelial cells) in the DTH inflammatory response.

Cheek island flap for replacement of critical limited defects of the upper aerodigestive tract.

Our experience thus far indicates that the island cheek flap is a satisfactory reconstructive method for small but critical defects in the upper aerodigestive tract. The mucosal lining is an ideal replacement for the lining of the mouth, pharynx, and esophagus. Only a single stage procedure is required. The surgical technique is relatively simple and does not unnecessarily prolong an extensive operation for tumor resection. We have found the procedure to be reliable with no instances of flap loss or necrosis.

Perforation of the colon in the immunocompromised patient.

Perforation of the colon in the immunocompromised patient is a catastrophic and usually fatal event. The immunocompromised patient, like all patients, may suffer from the more common causes of colonic perforation, including diverticulitis, chronic inflammatory bowel disease, presence of a foreign body, and trauma. There also appears to be in these patients the unusual occurrence of spontaneous perforation, particularly in patients with renal allografts or on dialysis. In a retrospective multi-hospital review, 10 cases of apparent spontaneous perforation were found. The pathogenesis is unclear, but predisposing factors include immunosuppressive medications, uremia, discrete colon ulcerations, and fecal impaction. The reported mortality rate approaches 100 percent due to delayed recognition and impaired host defense mechanisms. In our patients, mortality was 40 percent. We attribute this improved survival to prompt surgical intervention and aggressive postoperative management, including daily dialysis, parenteral hyperalimentation, broad-spectrum antibiotics, and a high index of suspicion for ongoing sepsis with early repeat exploration.

Aggressive surgical management of pyriform sinus carcinoma. A 15 year experience.

A total of 51 patients with pyriform sinus carcinoma were treated surgically. Fifty had pharyngolaryngectomy and radical neck dissection and 1 had a pharyngolaryngectomy. The surgical mortality was zero. No patients were lost to follow-up and all were followed for a minimum of 2 years. Stage IV patients had a 2 year survival rate of 15 percent and stage III patients, a 45 percent rate. Eighty-four percent of radical neck specimens contained involved nodes. The 2 year survival rates correlated with the number of pathologically involved nodes were as follows: 50 percent for those with zero to one node, 31 percent for two to three nodes, and 16 percent for four or more nodes. Perioperative radiotherapy increased the survival rate in those patients with zero to three involved nodes (47 percent survival rate with radiotherapy versus 25 percent without radiotherapy). Tumor recurrence was most frequent at the primary site (32 percent) and directly affected survival and control of disease elsewhere. Pyriform sinus carcinoma often presents with advanced local and nodal disease. Local control is essential, and adequate resection may require a cervical esophagectomy. Survival may be enhanced by the addition of radiotherapy in those patients with minimal nodal involvement.

Application of clinically valid cardiac risk factors to aortic aneurysm surgery.

The operative outcome of 97 consecutive nonruptured infrarenal aortic aneurysms is analyzed regarding clinically identifiable cardiac risk factors. Clinically evident coronary artery disease was present in 45 patients (46%). Operative mortality was 4% (four cardiac deaths) with an additional 4% nonfatal postoperative myocardial infarction rate. All cardiac complications occurred in patients with clinically evident coronary artery disease, while no mortality occurred in 52 patients lacking a preoperative history of myocardial infarction, congestive heart failure, or angina. Preoperative risk factors having a significant negative influence on outcome include a history of prior myocardial infarction and compensated congestive heart failure. Few patients with aneurysms who have clinical evidence of coronary artery disease are indicated for coronary arteriography and bypass prior to aneurysm repair. Furthermore, indications for invasive cardiac screening of the patient with an aneurysm who lacks cardiac symptoms are limited.

Assessment of immunocompetent cells in patients with head and neck squamous cell carcinoma.

Patients with squamous cell carcinoma of the head and neck have impaired T cell function and poor tumor-specific responsiveness. Disproportionate levels of circulating immunocompetent cells could be one reason for this diminished immunity. In this study, a panel of monoclonal antibodies and flow cytofluorometry were used to define the relative proportions of selected immune cell populations. We detected a deficiency of the interleukin-2-producing subset of T helper-inducer cells (TH 5.2+) in these patients. Our data showed no significant differences in circulating levels of total T cells, T cell subsets, B cells, monocytes, or natural killer cells when compared to age, alcohol- and tobacco-use matched controls.

Aortic and peripheral prosthetic graft infection: differential management and causes of mortality.

This report of 25 patients with prosthetic graft infection has compared the diagnosis, management, and outcome in 14 patients with infected aortic grafts with 11 patients with infected peripheral grafts (two axillofemorofemoral, five femorofemoral, five femoropopliteal, and one femoral interposition). Peripheral graft infection had a significantly shorter interval to diagnosis compared with aortic graft infection. Total graft removal combined with either autogenous revascularization or extraanatomic bypass using prosthetic graft was performed in all 14 patients with infected aortic grafts. Management of peripheral graft infection consisted of total graft removal in eight patients (four with autogenous revascularization and two with amputation) and partial graft removal in three patients (two with amputation). Mortality and amputation rates for infected aortic grafts were 43 percent and 25 percent, respectively compared with 36 percent and 27 percent for infected peripheral grafts. Recommendations for management of the infected aortic prosthetic graft include total graft removal, but methods and timing of revascularization are dependent on the specific features of the individual case. However, preferred management for the infected peripheral prosthetic graft includes total graft removal and, if indicated, revascularization using autogenous tissue.

Expression of I-region-associated antigen (Ia) and interleukin 1 by subcultured human endothelial cells.

Activation of T cells requires three signals from an antigen-presenting cell: antigen, Ia determinants (HLA-D region determinants in man), and interleukin 1 (IL-1). Recent evidence has suggested that macrophages, dendritic cells, epidermal Langerhan's cells, and endothelial cells can each function as antigen-presenting cells (APC). If these cell types can independently function as APC, they should synthesize Ia determinants and secrete IL-1. To determine if endothelial cells fulfill these requirements, we have propagated human umbilical vein endothelial cells by serial subculture for extended periods of time and assessed Ia expression and IL-1 secretion. The endothelial cells were subcultured for 8 months (approximately 20 subcultures) and were found to display classic morphology and immunofluorescent staining for the endothelial cell-specific marker Factor VIII-related antigen. In a separate paper we have shown that these subcultured endothelial cells can present antigen to T cells in a HLA-D region-restricted fashion (C. R. Wagner, R. M. Vetto, and D. R. Burger, Subcultured human endothelial cells can independently function as fully competent antigen-presenting cells, accepted for publication, Hum. Immunol.). In this paper we present evidence demonstrating that extensively subcultured endothelial cells biosynthesize both HLA-DR and HLA-DS molecules after exposure to T cells and antigen or to a supernatant from antigen-activated T cells. Evidence is also presented that when endothelial cells are cultured in the presence of lipopolysaccharide they secrete a molecule(s) with IL-1 activity as assayed by LBRM-33-IA5 cell line production of interleukin 2.

Subcultured human endothelial cells can function independently as fully competent antigen-presenting cells.

Recent evidence has suggested that dendritic cells, epidermal Langerhan's cells and endothelial cells (EC) as well as macrophages, fulfill the requirements of antigen-presenting cells. Despite a variety of controls, one weakness in the evidence that these latter cell types can independently serve as antigen-presenting cells is that the cell preparations may contain small numbers of contaminating macrophages or other cell types. The experiments described in this paper are directed towards providing firm evidence that human EC are independently capable of presenting antigen to T cells. EC were isolated from human umbilical veins and maintained continuously by serial subculture for periods of up to 8 months. The subcultured EC displayed classic EC morphology and uniform immunofluorescent staining for Factor VIII-related antigen. The subcultured EC (tested to the 18th subculture) presented both particulate and soluble antigens to macrophage-depleted T cells with an efficiency equivalent to freshly isolated cells. Monoclonal antibodies to HLA-DR and HLA-DS determinants inhibited antigen presentation by either autologous macrophages or EC. In addition, antigen presentation by the subcultured EC was not affected by the macrophage-specific monoclonal antibody Mac-120, which inhibited antigen presentation by autologous macrophages in the same experiments. These results are consistent with human EC being able to independently function as fully competent antigen-presenting cells.

Vascular endothelial cells in cell-mediated immunity: adoptive transfer with in vitro conditioned cells is genetically restricted at the endothelial cell barrier.

Delayed-type hypersensitivity (DTH) is a cell-mediated immune response that can be adoptively transferred in rats when greater than 2 X 10(8) cells from peritoneal exudate, lymph nodes, or spleen are used. We have shown that by using an in vitro conditioning step with antigen, transfer can be subsequently carried out with as few as 2 X 10(7) spleen cells. The magnitude of DTH was reflected in ear swelling after intradermal injection of antigen [tuberculin or keyhole limpet hemocyanin (KLH)] and confirmed histologically. The transfer was antigen specific, requiring the sensitizing antigen in both the in vitro conditioning step and in the ear test challenge. Adoptive transfer with conditioned cells was genetically restricted by alleles of the RT-1 region [major histocompatibility complex (MHC) of the rat]. Brown Norway strain (n haplotype) immune cells would not transfer DTH to Lewis (1 haplotype), ACI (a haplotype), or Buffalo (b haplotype) rats, whereas each strain would transfer DTH to syngeneic recipients. Moreover, this pattern of restriction held for all strains when tested in reciprocal fashion. In additional experiments, F1 to parental bone marrow chimeras were constructed so that bone-marrow-derived cells and non-bone-marrow-derived cells were of different RT-1 haplotypes. When these chimeras were used as recipients, transfer of DTH was only observed when immune donor cells and recipient non-bone-marrow-derived cells were syngeneic. These results point to the critical role of non-bone-marrow-derived cells (endothelial cells) in the DTH reaction.

The mechanism of antigen presentation by endothelial cells.

Endothelial cells line the vessels and lymphatics forming a barrier between circulating T cells and the extravascular tissue site of antigen. We have suggested that circulating T cells recognize antigen on the surface of endothelial cells, resulting in the activation of the endothelium such that the endothelial cells then release the key mediators of a cell-mediated immune response. To test this hypothesis, we have evaluated the extent to which endothelial cells can signal antigen-specific T cell activation. We have shown that cultured endothelial cells are as effective as macrophages in lymphocyte activation and that this activation is HLA-DR restricted. In additional experiments we have established that endothelial cells synthesize both Ia and IL-1 early in the signaling process. To eliminate any possible contribution of other cell types participating in the T cell-endothelial cell interaction, we have shown that cloned endothelial cells present antigen to cloned T cells. Moreover, there appeared to be a preference of selected T-cell populations for different types of antigen presenting cells. These experiments document that endothelial cells are independently competent antigen presenting cells.