Human villous adenomas engrafted into scid mice survive for prolonged period without malignant transformation.

Human villous adenomas are thought to represent premalignancies that subsequently give rise to colorectal adenocarcinomas. Currently there is no in vivo model in which to study the dedifferentiation and malignant transformation of these tumors. We establish here that human villous adenomas can be successfully engrafted into severe combined immunodeficient (scid) mice. Furthermore, these xenografts remain viable for up to 18 mo after either a subcutaneous or intraperitoneal inoculation of the human tissue. Tumors grew slowly and secreted a clear mucinous fluid. Examination of the tumors histologically at 1, 4, and 12 mo after implantation revealed that the villous polypoid structure was maintained and islands of atypical cells were observed within pockets of mucin surrounding the adenomatous tissue. No gross or histologic evidence of malignancy was detected throughout the 20-mo observation period. The human identity of the cells in the graft was confirmed by DNA in situ hybridization with a human-specific probe. We conclude that the human-scid xenograft described here represents a viable animal model with which to study the potential malignant dedifferentiation of villous adenomas over a prolonged period of time and to evaluate the possible contribution of selected oncogenic vectors on the malignant transformation of these adenomas.

Post-OKT3 induction therapy CD complex response predicts renal allograft rejection.

CD complex response to cessation of induction with OKT3 may be predictive of rejection. Twenty-seven patients receiving renal allografts and OKT3 induction immunosuppression were retrospectively analyzed for CD complex repopulation and allograft rejection. Flow cytometric monitoring was utilized in all patients. Responder status groups were identified based on CD complex repopulation, with fast responders demonstrating CD complex repopulation above the determined cohort mean. Slow responders had repopulation below this mean. Student's t test yielded P<0.01 (CD2), P<0.02 (CD3), and P<0.01 (CD8). Nonresponder patients were identified with repopulation below the mean, but flat compared with depletion. All nine fast responders lost their graft or were treated for rejection. No slow responder experienced graft loss or rejection episodes. One nonresponder was treated for rejection. CD complex activity following OKT3 cessation correlates with future rejection. Identification of responder status provides insight into propensity to reject, allowing individual tailoring of immunosuppression to patient response.

Xanthine oxidase inhibition after resuscitated hemorrhagic shock restores mesenteric blood flow without vasodilation.

To determine the contribution of xanthine oxidase-mediated reperfusion injury to the blood flow deficits seen in the intestinal microcirculation after resuscitated hemorrhagic shock, rats were prepared for intravital microscopic study then bled to 50% of baseline blood pressure for 60 min. Treatment animals received a 50 mg/kg bolus and a 25 mg/kg/h infusion of the xanthine oxidase inhibitor allopurinol after shock but before standard resuscitation with shed blood and an equal volume of Ringer's lactate. A similarly resuscitated group served as control. Blood flow and vessel diameters were measured in the neurovascularly intact terminal ileum using intravital microscopy and doppler velocimetry. Resuscitation restored cardiac output and blood pressure in both groups. Blood flow in first order arterioles 120 min postresuscitation was 41% of baseline in the standard resuscitation group and 77% of baseline in the allopurinol-treated group. A1 arteriolar diameter was not significantly different between the two groups, being 73 and 82% of baseline, respectively. These data suggest that xanthine oxidase-mediated ischemia-reperfusion injury contributes to blood flow deficits in the small intestinal microcirculation after resuscitated hemorrhagic shock and that the improvement in blood flow seen with allopurinol is not due to vasodilation within the microvasculature.

Left-to-right shunts in control of bleeding following surgery for aneurysms of the ascending aorta.

Surgical repair of complex thoracic aneurysms requiring aortic valve replacement and coronary revascularization is occasionally complicated by significant bleeding despite the experience of the surgeon. While bleeding from the mediastinal tissues and the anterior suture line is usually easily controlled, posterior bleeding may require dismantling the repair and a second bypass run. The synergism of a second bypass run and continued bleeding may result in increased mortality and/or morbidity. We recently encountered bleeding in a patient who developed ventricular dysfunction after bypass and opted to interpose a Gore-tex graft between the aneurysm wall and the right atrium with immediate hemostasis and a benign course. Subsequently we used four different shunts successfully in 9 of 33 patients. The average bleeding rate 30 minutes after protamine was 221 +/- 60 ml/minute with a range of 190 to 350 ml/minute. The initial two hour chest tube drainage averaged 880 +/- 285 ml with a range of 490 to 1300 ml. There were no re-explorations for bleeding. The shunt in the first patient has remained open without cardiac decompensation. The last patient developed heart failure and required elective repair of a leak at the descending end of an arch replacement. Our experience suggests that these shunts can be effective, particularly if posterior suture line bleeding is encountered.

Reappraisal of empyema thoracis. Surgical intervention when the duration of illness is unknown.

The timing of surgical treatment of empyema remains controversial. Traditionally, thoracotomy is performed either within three weeks of diagnosis or delayed until presumed pleurodesis occurs. Often, these patients are moribund and the duration of illness impossible to determine. We report our surgical results in seven patients with a deteriorating clinical course and multiple loculations which persisted after tube thoracostomy and would not have responded to multiple thoracostomies. Five patients required decortication. One required lobectomy for an abscess which developed on the contralateral side six weeks after discharge. There were no deaths or recurrences of empyema. Average times from surgery to tube removal and to discharge were six to 12 days, respectively. We conclude that one can safely and cost-effectively treat these patients surgically even when the duration of illness and presence of pleurodesis are unknown, and that the postoperative course will be uncomplicated.

Combination of cyclosporine and splenectomy suppresses interleukin-6 production and major histocompatibility complex class II expression and prolongs cardiac xenograft survival.

Although untreated Lewis rat recipients will reject a transplanted hamster heart in 3 days, accommodation of heart xenografts can be induced by treatment with cyclosporine and splenectomy, improving graft survival to greater than 50 days. Both humoral and cellular arms of the immune system may be involved in the mechanisms responsible for the prolongation of graft survival. Our objective was to study the impact of cyclosporine and splenectomy on the deposition of antibodies, complement, or both within the graft. We also compared the cellular component of inflammation in treated recipients with that in untreated controls. Inbred male Lewis rats given cyclosporine 15 mg/kg per day were splenectomized 2 days after they had received heterotopic heart transplants from Golden Syrian hamsters. Recipients of syngeneic grafts or untreated xenografts served as controls. Plasma interleukin-6 activity was measured in a standard proliferation assay with 7TD1 hybridoma cells. Deposition of immunoglobulin M, immunoglobulin G, and complement in heart tissue was evaluated by immunofluorescence. Cells infiltrating the graft that expressed major histocompatibility complex class II antigens were identified by immunohistochemical staining with OX6 antibodies. In xenograft recipients receiving immunosuppression, interleukin-6 activity, immunoglobulin M and complement deposition were significantly reduced, graft infiltration was mild, and cardiac function was good compared with the results in those without treatment 3 and 10 days after implantation. Inflammatory cells expressing major histocompatibility complex class II antigens were significantly reduced in immunosuppressed xenograft recipients (2.8 +/- 0.4 cells/high power field) compared with those in xenogeneic controls (9.5 +/- 0.6 cells/high power field; p < 0.0005). The significant decrease in deposition of humoral components (immunoglobulin M and complement), interleukin-6 plasma levels, and expression of major histocompatibility complex class II antigens by inflammatory cells within the nonrejecting grafts suggests that the synergistic benefit of cyclosporine and splenectomy depends on the attenuation of both cellular and humoral mechanisms of xenograft rejection.

The prostaglandin response to cholesterol feeding by the rabbit gallbladder in vitro.

Eleven rabbits (five female, six male) were fed a high (2%) cholesterol diet for 2 weeks. Twelve control rabbits (six female, six male) were fed standard rabbit chow. As expected, the cholesterol feeding raised serum and bile cholesterol concentrations and increased the lithogenic indexes. The gallbladders were harvested, and the mucosa and serosa were separately exposed to arachidonic acid in an in vitro incubation chamber at 37 degrees C. Cholesterol feeding stimulated the rates of synthesis of PGI2, but this effect was limited to the serosa (and not the mucosa) of gallbladders from female (but not male) animals. In contrast, cholesterol did not induce any changes in PGE biosynthesis.

The effects of dimethyl sulfoxide on aortic prostacyclin production and serum thromboxane and plasma fibrinogen levels in rabbits fed a normal versus a cholesterol-enriched diet.

Through an unknown mechanism, dimethyl sulfoxide (DMSO) retards atherogenesis in cholesterol-fed rabbits (CFR). We studied the effects on the development of lesions and prostacyclin (PGI2) production in the thoracic aorta and total serum lipid and cholesterol content of the abdominal aortic serum thromboxane (TXB2) and plasma fibrinogen levels in rabbits fed control versus atherogenic diets, with and without DMSO. Without DMSO, PGI2 production was significantly higher in CFR versus control animals (8.65 +/- 1.0 vs 6.38 +/- 0.3 ng/15 min [p less than 0.02]). DMSO did not influence PGI2 production in any of the groups but significantly reduced the number of atheromatous lesions in CFR (78% +/- 9% vs 8% +/- 4% [p less than 0.001]). With DMSO, CFR had a significant reduction in total lipid levels (422 +/- 5 vs 300 +/- 21 mg/gm dry wt [p less than 0.01]) and cholesterol levels (74 +/- 12.8 vs 31.8 +/- 6.4 mg/gm dry wt [p less than 0.01]) compared with control animals. Fibrinogen levels were significantly lower in CFR versus control animals (0.83 +/- 0.07 vs 2.42 +/- 0.13 mg/ml [p less than 0.01]). TXB2 was lower in DMSO plus control versus control animals alone. In conclusion, DMSO does not appear to act through changes in PGI2 or fibrinogen activity. Its effect in lowering TXB2 in CFR suggests an action on platelet function.

Effects of female sex hormones and pregnancy on gallbladder prostaglandin synthesis.

To investigate whether female sex hormones and pregnancy induce increased gallbladder synthesis of prostaglandin I2 (PGI2) and prostaglandin E (PGE), we used an in vitro incubation chamber to quantitate the effects of progesterone, estrogen, pregnancy, and pregnancy plus a 2%-cholesterol diet on mucosal and serosal PGI2 and PGE production by the rabbit gallbladder. Neither the female sex hormones nor pregnancy alone caused a significant increase in PGI2 or PGE synthesis. The gallbladders of cholesterol-fed, pregnant rabbits demonstrated significant increases only in serosal synthesis of PGI2. This increased production was equivalent to that noted for gallbladders from nonpregnant rabbits fed a high-cholesterol diet. There were no increases in mucosal synthesis of PGE or of PGI2. Thus, neither elevated levels of progesterone or estrogen nor pregnancy is directly responsible for the increased PGI2 activity in the female gallbladder; conversely, this effect seems to be mediated by the increased biliary concentrations of cholesterol.

Can patients with minor head injuries be safely discharged home?

To identify all patients with serious intracranial injury, current treatment strategies include admission and/or computed tomographic evaluation of all patients with head injuries. However, the majority of patients with head injuries who are awake do not require subsequent intervention. A review of 407 consecutive patients with head injuries treated at an adult regional trauma center identified 310 patients with Glasgow Coma Scores of 15 in the emergency department, all of whom were admitted. Five patients with Glasgow Coma Scores of 15 required intervention for intracranial abnormality. All five patients had skull fractures and/or neurologic deficits. Based on this and other studies, criteria for discharge from the emergency department are a Glasgow Coma Score of 15, no deficit except amnesia, no signs of intoxication, and no evidence of basilar fracture on clinical examination or linear fracture on screening skull roentgenography. Safe discharge without universal computed tomographic evaluation or admission is possible and cost-efficient.

Endocrine organ metastases in subjects with lobular carcinoma of the breast.

OBJECTIVE: To define the frequency and pattern of endocrine organ metastases in patients dying of invasive lobular carcinoma. DESIGN: Postmortem microscopic evaluation of the ovaries and adrenal, pituitary, thyroid, and parathyroid glands for breast cancer metastases. SETTING: Roswell Park Cancer Institute, Buffalo, NY, between 1971 and 1990. SUBJECTS: One hundred eighteen subjects who died of their cancer: 86 had infiltrating ductal carcinoma; 32, invasive lobular carcinoma. MEAN OUTCOME MEASURE: Quantitative measurements to allow frequency determinations and statistical comparisons. RESULTS: Endocrine organ metastases were found in 91% of the subjects with invasive lobular carcinoma vs 58% of subjects with infiltrating ductal carcinoma. The adrenal gland was most frequently involved. Multiple endocrine metastases were most common in the group with invasive lobular carcinoma. CONCLUSIONS: A relationship exists between invasive lobular carcinoma and endocrine metastases. This indicates that antemortem endocrine evaluation may subsequently improve quality-of-life treatment.

Cardiac papillary fibroelastomas: rationale for excision.

We experienced a case of papillary fibroelastoma of the left ventricular outflow tract in a patient with severe valvular heart disease that was detected only by transesophageal echocardiography. Preoperative detection of this lesion altered the surgical procedure to include resection of the mass through the aortic valve annulus along with repair/replacement of the valves. The literature documents sufficient morbidity/mortality to support excision of these lesions regardless of symptoms or location.

Calcified ball thrombus in the left atrium.

We experienced a case of calcified ball thrombus that was fixed to the atrial septum in the left atrium. This patient had no symptoms and no cardiac dysfunction. the thrombus was detected during preoperative work-up of a retroperitoneal tumor. The process of fixation to the atrial septum and calcification is unclear.

The surgical management of empyema thoracis in substance abuse patients: a 5-year experience.

Postpneumonic empyema (EMP) may develop in substance abuse patients, requiring prolonged hospitalization. An algorithm that provides quality care and a rational basis for timely surgical intervention would be advantageous. We report our five-year experience with EMP in substance abuse patients and present such a treatment plan. Sixty-one substance abuse patients were treated for EMP. Posteroanterior, lateral, and decubitus x-ray studies were obtained before treatment to assess fluid movement. Chest tubes were placed to drain frank pus and to obtain material for positive smears. X-ray studies and computed tomography were done 24 hours later to assess parenchymal pathology and to detect any multiple loculations. Thirty-three substance abuse patients recovered following initial tube thoracostomy and 7 after a second chest tube was introduced. Twenty-one had multiple loculations and underwent thoracotomy. Twenty of the 21 required extensive debridement or decortication, or both; 2 required lobectomy and 1 pneumonectomy. Chest tubes were removed on an average of 6 +/- 1.5 days. Average postoperative stay was 10.7 +/- 2 days. There were 2 early deaths and 1 late death and no recurrent EMP. Bacteriology findings were nonspecific and often polymicrobial. We conclude that early thoracotomy can be lifesaving in the presence of a benign clinical course.

Beneficial effects of fluosol-polyethylene glycol cardioplegia on cold, preserved rabbit heart.

BACKGROUND: Because of its high oxygen-carrying capacity, especially at low temperatures, fluosol may enhance heart preservation. METHODS: Hearts of male New Zealand white rabbits (1.5-2.0 kg) were excised and flushed through the aorta with 0 degree C St. Thomas' Hospital solution, fluosol, or polyethylene glycol or fluosol-polyethylene glycol cardioplegic solution. Hearts were then stored for 12 hours at 0 degree C and reperfused with Krebs-Henseleit buffer at 36.5 degrees C for 60 minutes using a Langendorff system. RESULTS: Myocardial contractile function was significantly greater in the fluosol-polyethylene glycol cardioplegia-preserved group (p < 0.01) and polyethylene glycol-cardioplegia preserved group (p < 0.05) than in the St. Thomas' Hospital solution-preserved group. The myocardial high-energy phosphate content was significantly higher in the fluosol-polyethylene glycol-cardioplegia-preserved group (p < 0.01), with reduced release of lactate dehydrogenase (p < 0.01) in comparison with the St. Thomas' Hospital solution-preserved group. CONCLUSIONS: The addition of fluosol and polyethylene glycol to the cardioplegic solution may enhance long-term cold heart preservation.

The temporal relationship in arterial and venous prostacyclin and thromboxane activity during 24 hours of intraaortic balloon counterpulsation in dogs.

We studied the effects of intraaortic balloon counterpulsation (IABCP) on prostacyclin (PGI2) and thromboxane (TXB2) levels in dogs during 24 hours of 1:1 IABCP or a sham procedure in which the balloon was positioned but left deflated. The arterial PGI2 levels in the IABCP group increased from control values of 95 +/- 20 pg/ml to 268 +/- 95 pg/ml at 1 hour, 429 +/- 95 pg/ml at 4 hours, and 1,884 +/- 532 pg/ml at 24 hours. The arterial PGI2 levels were consistently higher in the IABCP group. Although the TXB2 measurements revealed no significant differences between groups, the IABCP group consistently had a higher level than the sham group. The platelet count in the control group decreased to 45% of baseline levels versus 55% for the IABCP group. We conclude that prolonged IABCP results in either net production of PGI2 or decreased degradation. The correlation between TXB2 and platelet counts is unclear and remains to be defined.

Pathologic aspects of polytetrafluoroethylene sutures in human heart.

BACKGROUND: Polytetrafluoroethylene (PTFE) sutures have been widely used as a mitral chord substitute. We present the cases of 4 patients who underwent mitral valve repair with chordal replacement by PTFE sutures and these required another operation. This gave us the chance to examine the PTFE sutures. METHODS: Structural analysis of the PTFE sutures was performed 26 to 378 days postoperatively. The specimens were examined grossly, microscopically, and by scanning or transmission electron microscopy or both. RESULTS: The PTFE suture in 1 patient was found to be completely covered with endothelial cells 154 days postoperatively. There was no calcification, and the flexibility and pliability of the PTFE sutures was preserved. Even though the PTFE sutures seemed uncovered on visual inspection, there was a thin lining of collagen and fibrin on the surface. Endothelial cells were seen in areas that looked clear in one specimen 26 days postoperatively. CONCLUSIONS: We think that the new layer of collagen could be promising in terms of durability and that the endothelial layer wil resemble normal tissue in its anticoagulant properties.

Synchronicity, multicentricity, and metachronicity of head and neck cancer.

Two hundred patients with squamous carcinoma of the head and neck were evaluated prospectively for synchronous second primary tumors. Complete head and neck examination, chest x-ray, and barium study (when indicated) revealed synchronous tumors of the upper aerodigestive tract in 24 patients (12%). Eleven patients had a second primary in the head and neck area. Nine patients had carcinoma of the lung, while four had carcinoma of the esophagus. Seven patients had a second primary outside the upper aerodigestive tract either in large bowel or prostate. During the period of this study, an additional 13 patients were seen with metachronous tumors 1-12 years after initial treatment of their index tumor. Most of these metachronous tumors were in the lung and esophagus and were noted within 1-3 years of treatment of the primary head and neck cancer. Detection of synchronous second primary is very important for prognosis and management of the index tumor, while early diagnosis of metachronous lesion is crucial in the follow-up of these patients.

Prolonged enteral nutrition in malnourished patients with nonelemental feeding. Reappraisal of surgical technique, safety, and costs.

In a 2 year period, 60 consecutive feeding enterostomies were placed in malnourished patients. The major complication rate was 1.6 percent. Total complications were 8 percent. Thirty day mortality was 13 percent. Nearly all patients were given isosmotic nonelemental diets. The incidence of diarrhea was 2 percent with this regimen. Four of five patients given elemental diets had diarrhea. Serum albumin levels increased significantly from a preoperative mean of 2.75 to 3.03 g/dl. Best overall results were achieved in patients undergoing upper gastrointestinal surgery or pancreatobilary procedures for nonmalignant lesions. More than $60,000 was saved in 2 years by substituting isosmotic formulas for elemental ones. It appears that many patients are given elemental formulas who do not actually require them. Since isosmotic solutions will not infuse through needle catheters, we advocate placing 12 F. catheters and have documented the safety of this change. By using these larger catheters, the surgeon will not lose the option of using isosmotic preparations. We have shown these preparations to be nutritionally effective with a marked lessening of diarrhea and a cost approximately a sixth of that of elemental products.

Avoiding laparotomy in nonsurgical pneumoperitoneum.

Patients with free intraperitoneal air collections usually undergo emergency surgery, and the majority will have a gastrointestinal tract perforation. However, there is a subset of patients in whom no identifiable perforation is found at surgery. This entity of noniatrogenic, nonsurgical spontaneous pneumoperitoneum is being diagnosed more frequently at present and is commonly associated with other disease processes that, together, may suggest a benign process. Therefore, a diagnostic algorithm that would preclude operative intervention in this cohort of patients would be of paramount clinical importance. In this report, we present representative cases of the most common types of nonsurgical pneumoperitoneum, review the pathogenesis of this disorder, and discuss its relationship with pneumatosis cystoides intestinalis, pulmonary disorders, scleroderma, and gynecologic processes. Finally, we outline a diagnostic algorithm that may identify patients who can safely be observed, thereby reducing the incidence of negative laparotomies and, secondarily, the aggregate cost of health care.