Analysis of Risk Factors for Allograft Outcome Comparing 2 Kidneys From the Same Donor in Separate Recipients.

BACKGROUND: An analysis of 2 kidney transplants from the same donor at the same center enables us to analyze the influence of risk factors on the outcome of the grafts in different recipients. METHODS: We retrospectively analyzed 88 kidneys from 44 donors that were implanted in 88 recipients at our institution between 2007-2016. We defined unsatisfactory outcome as glomerular filtration rate <30 mL/min/1.73 m2 allograft loss or recipient death within the first year after transplantation. Fifty-three kidneys were allocated and age-matched to donors above the age of 65 years (via Eurotransplant Senior Program or center offer). We compared kidney pairs with satisfactory outcome in both recipients (group A) to pairs with divergent outcome (group B) and unsatisfactory outcome in both recipients (group C). RESULTS: Thirty-four grafts (17 donors) had a satisfactory outcome for both recipients (group A), and 16 grafts (8 donors) had an unsatisfactory outcome for both recipients (group C). Donor age was significantly higher in group C vs group A (67.5 ± 6.7 vs 56.4 ± 16.0 years, P = .010). The 19 donors donating 1 kidney with satisfactory and the other with unsatisfactory outcome were 67.4 ± 10.7 years old (group B). A severe surgical complication occurred more often in recipients with an unsatisfactory outcome in comparison to patients with a satisfactory outcome. CONCLUSION: Donor age is an important risk factor for an unsatisfactory outcome, either in one or both kidneys of the same donor.

[Hemichorea with Contralateral High Signal Intensity Putaminal Lesion on T1-Weighted Images in Non-Ketotic Hyperglycemia]. / Hemichorea mit T1-hyperintenser Signalalteration im kontralateralen Putamen bei nichtketotischer Hyperglykämie.

A 64-year-old diabetic female patient presented with involuntary unilateral hyperkinetic movements of the left limbs. Cranial MRI showed a contralateral high signal intensity putaminal lesion on T1-weighted images without any signal changes in the T2-weighted images. This finding is characteristic for hemichorea-hemiballism associated with insufficiently treated diabetes mellitus. Additionally, proton MR spectroscopy was performed and revealed a decreased N-acetylaspartate/creatine and N-acetylaspartate/choline ratio, indicating neuronal damage of the contralateral putamen.

Effect of meaning on apraxic finger imitation deficits.

Apraxia typically results from left-hemispheric (LH), but also from right-hemispheric (RH) stroke, and often impairs gesture imitation. Especially in LH stroke, it is important to differentiate apraxia-induced gesture imitation deficits from those due to co-morbid aphasia and associated semantic deficits, possibly influencing the imitation of meaningful (MF) gestures. To explore this issue, we first investigated if the 10 supposedly meaningless (ML) gestures of a widely used finger imitation test really carry no meaning, or if the test also contains MF gestures, by asking healthy subjects (n=45) to classify these gestures as MF or ML. Most healthy subjects (98%) classified three of the 10 gestures as clearly MF. Only two gestures were considered predominantly ML. We next assessed how imitation in stroke patients (255 LH, 113 RH stroke) is influenced by gesture meaning and how aphasia influences imitation of LH stroke patients (n=208). All patients and especially patients with imitation deficits (17% of LH, 27% of RH stroke patients) imitated MF gestures significantly better than ML gestures. Importantly, meaningfulness-scores of all 10 gestures significantly predicted imitation scores of patients with imitation deficits. Furthermore, especially in LH stroke patients with imitation deficits, the severity of aphasia significantly influenced the imitation of MF, but not ML gestures. Our findings in a large patient cohort support current cognitive models of imitation and strongly suggest that ML gestures are particularly sensitive to detect imitation deficits while minimising confounding effects of aphasia which affect the imitation of MF gestures in LH stroke patients.

Fewer cytomegalovirus complications after kidney transplantation by de novo use of mTOR inhibitors in comparison to mycophenolic acid.

BACKGROUND: Cytomegalovirus (CMV) is a risk factor for patient and graft survival after kidney transplantation. METHODS: We retrospectively analyzed risk factors for CMV infection in 348 patients who received a kidney transplant donated after brain death (n = 232) or by living donation (n = 116) between 2008 and 2013. Of the 348 patients analyzed, 91 received a mammalian target of rapamycin inhibitor (mTORi)-based immunosuppressive regimen. A total of 266 patients were treated with standard immunosuppression (Group 1) consisting of basiliximab induction, calcineurin inhibitor (CNI), and either mycophenolic acid (MPA, n = 219) or everolimus (EVE) (n = 47). We also included 82 patients who received more intense immunosuppression (Group 2) with lymphocyte depletion, CNI, plus either MPA (n = 38) or EVE (n = 44). Only patients in the high-risk constellation received CMV prophylaxis in Group 1, while all patients in Group 2 received prophylaxis for 6 month. RESULTS: The overall rate of CMV infections was low with 10.1% in all patients. Despite the different prophylaxis strategies applied, no difference was seen in CMV infections between Group 1 (10.9%) and Group 2 (13.6%). A multivariate analysis revealed that patients on EVE had fewer CMV complications compared with patients on MPA (P = 0.013, odds ratio [OR] 4.8, confidence interval [CI] 1.4-16.5). Donor and recipient age >65 years was an independent risk factor (P = 0.002, OR 3.2, CI 1.5-6.7) for CMV infections. Patients with CMV infections had significantly worse graft function after 2 years (P = 0.001). CONCLUSION: CMV is a significant risk factor for long-term graft outcome. Patients treated with EVE developed fewer CMV complications compared to patients on MPA. The use of mTORi is useful in patients at high risk of developing CMV infections.

Ambulatory long-term pH monitoring in pigs.

BACKGROUND: pH monitoring has been established as the "gold standard" in the diagnosis of gastroesophageal reflux. Evaluation of experimental antireflux therapy should therefore also include this technique, but a suitable technique in an experimental model did not exist so far. The aim of our study was to establish a reliable method for the evaluation of an experimental reflux model in pigs. METHODS: A total of 33 German Landrace pigs with an average body weight of 56 (50.2-67.2) kg were included. pH monitoring was performed before and after open cardiomyotomy in each animal. All manipulations were performed under general anesthesia. After manometric localization of the gastroesophageal high-pressure zone, a standard pH probe was inserted into the pharynx through a small needle-punctured canal on the side of the animal's snout and placed under endoscopic guidance with the proximal sensor 3 cm above the lower esophageal sphincter (LES) and the distal sensor in the stomach for reference. The harness to carry the pH recorder on the animal's back consisted of a modified belly strap that enabled the animal to move around without limitation. For analysis the same threshold levels were defined as in humans. Gastroesophageal reflux was induced by cardiomyotomy. RESULTS: The placement of the standard pH probe was possible in all cases. Inserting the probe on the side of the snout left the animals free to nuzzle, which complies with the normal habits of pigs, without breaking the probes and without being compromised in their natural behavior. Repeated punctures for multiple measurements were easily feasible. We performed up to three examinations in each individual animal. Recording was performed for 48 h. A mean number of 67.3 (+/-9.7) acidic refluxes were registered. The mean number of long acidic refluxes was 3.2 (+/-0.75). For an average total time of 75.5 (+/-14.3) min the pH was below 4 accounting for a fraction time pH below 4 of 3.5% (+/-0.68%). Following cardiomyotomy the number of acidic refluxes increased significantly to 166.1 (+/-21.8) and the number of long refluxes to 17.74 (+/-3.35). The total time of pH below 4 increased to 371.3 (+/-62) min so that the fraction time pH below 4 was 14.5% ( p = 0.0006). CONCLUSION: pH monitoring should be mandatory in any investigation of antireflux therapy. Our method is easy and secure to perform. It is suitable for other gastrointestinal investigations (Bilitec, long-term manometry) that could be carried out using the same technique. The described data represent the basis for other investigations of experimental antireflux therapy.

Is there still a need for living-related liver transplantation in children?

OBJECTIVE: To assess and compare the value of split-liver transplantation (SLT) and living-related liver transplantation (LRT). SUMMARY BACKGROUND DATA: The concept of SLT results from the development of reduced-size transplantation. A further development of SLT, the in situ split technique, is derived from LRT, which itself marks the optimized outcome in terms of postoperative graft function and survival. The combination of SLT and LRT has abolished deaths on the waiting list, thus raising the question whether living donor liver transplantation is still necessary. METHODS: Outcomes and postoperative liver function of 43 primary LRT patients were compared with those of 49 primary SLT patients (14 ex situ, 35 in situ) with known graft weight performed between April 1996 and December 2000. Survival rates were analyzed using the Kaplan-Meier method. RESULTS: After a median follow-up of 35 months, actual patient survival rates were 82% in the SLT group and 88% in the LRT group. Actual graft survival rates were 76% and 81%, respectively. The incidence of primary nonfunction was 12% in the SLT group and 2.3% in the LRT group. Liver function parameters (prothrombin time, factor V, bilirubin clearance) and surgical complication rates did not differ significantly. In the SLT group, mean cold ischemic time was longer than in the LRT group. Serum values of alanine aminotransferase during the first postoperative week were significantly higher in the SLT group. In the LRT group, there were more grafts with signs of fatty degeneration than in the SLT group. CONCLUSIONS: The short- and long-term outcomes after LRT and SLT did not differ significantly. To avoid the risk for the donor in LRT, SLT represents the first-line therapy in pediatric liver transplantation in countries where cadaveric organs are available. LRT provides a solution for urgent cases in which a cadaveric graft cannot be found in time or if the choice of the optimal time point for transplantation is vital.

Generation of multiple angiogenesis inhibitors by human pancreatic cancer.

A primary inoculum of human pancreatic cancer cells (BxPC-3) has the ability to inhibit the growth of a secondary tumor in an in vivo animal model. Such ability suggests that the primary tumor is producing inhibitors that act at the site of the secondary tumor. Accordingly we attempted to discover which inhibitors are produced by pancreatic cancer cells. We determined that pancreatic cancer cells process angiostatin isoforms from plasminogen. Additionally, we isolated and characterized an uncleaved "latent" antiangiogenic antithrombin (aaAT) molecule processed from systemically available AT by pancreatic cancer cells as well as a cleaved form of aaAT processed from systemically available AT by pancreatic cancer cells. Human AT, cleaved with human neutrophil elastase, inhibits angiogenesis in the chorioallantoic membrane assay. This human aaAT molecule is able to inhibit the growth of pancreatic tumors in immune-compromised mice. Our work represents the first demonstration of multiple angiogenesis inhibitors from a single tumor and suggests that antiangiogenic therapies may provide an avenue for future treatment of pancreatic cancer.

Heterogeneity of angiogenic activity in a human liposarcoma: a proposed mechanism for "no take" of human tumors in mice.

BACKGROUND: Tumor cells are known to be heterogeneous with respect to their metastatic activity, proliferation rate, and activity of several enzymes. However, little is known about the heterogeneity of tumor angiogenic activity. We investigated whether heterogeneity of angiogenic activity could be responsible for the well-known observation of "no take" of human tumors transplanted into immunodeficient mice. METHODS: Severe combined immunodeficient (SCID) mice were xenotransplanted subcutaneously with tumor tissue (n = 55) or cell suspension of a human liposarcoma cell line (SW-872) or subclones (n = 28), with varying cell proliferation rates. Xenograft tumor growth was recorded for up to 6 months. Tumor tissues were then removed and analyzed for tumor cell apoptosis, microvessel density, and cell proliferation. All statistical tests were two-sided. RESULTS: Pieces of tumor derived from the parental cell line or its clones gave rise to three kinds of tumors: 1) highly angiogenic and fast-growing (aggressive) tumors, 2) weakly angiogenic and slow-growing tumors, and 3) nonangiogenic and stable tumors. Most tumors retained the original phenotype of their parental tumor. Tumor volume correlated positively with microvessel density (Spearman correlation coefficient [r] =.89; P< or =.0001) and inversely with tumor cell apoptosis (Spearman r = -.68; P =.002). Tumor volume was less strongly but still positively correlated with tumor cell proliferation in vivo (Spearman r =.55; P =.02). CONCLUSIONS: Human liposarcoma cells appear to be heterogeneous in their angiogenic activity. When tumor cells with little or no angiogenic activity are transplanted into SCID mice, a microscopic, dormant tumor results that may not grow further. Because such tiny tumors are neither grossly visible nor palpable, they have previously been called "no take." The finding that an angiogenic tumor can contain subpopulations of tumor cells with little or no angiogenic activity may provide a novel mechanism for dormant micrometastases, late recurrence, and changes in rate of tumor progression.

Effect of antiangiogenic therapy on slowly growing, poorly vascularized tumors in mice.

BACKGROUND: Angiogenesis is essential for tumor growth and progression. Therefore, inhibition of angiogenesis is being studied as a new anticancer therapy. Because cytotoxic chemotherapy is more effective on rapidly growing tumors than on slowly growing tumors, it has been assumed that antiangiogenic therapy will also be effective only on rapidly growing, highly vascularized tumors. We compared the effects of two angiogenesis inhibitors, TNP-470 and angiostatin, on slowly growing, poorly vascularized and rapidly growing, highly vascularized human tumors in mice. METHODS: Slowly growing (RT-4) and rapidly growing (MGH-U1) human bladder carcinoma cell lines were grown in severe combined immunodeficiency mice. Established tumors were treated with one of the two angiogenesis inhibitors. Tumor volumes, vascularity, and proliferation indices were determined. The in vitro effects of TNP-470 and of angiostatin on the proliferation of RT-4 and MGH-U1 cells were also investigated. All statistical tests were two-sided. RESULTS: RT-4 and MGH-U1 tumor growth was statistically significantly inhibited by both angiogenesis inhibitors (P<.001). Both inhibitors decreased the blood vessel density in both tumor types but did not alter the in vivo proliferation indices of the tumors. TNP-470, but not angiostatin, marginally decreased the in vitro proliferation of MGH-U1 cells. CONCLUSION: Slowly growing, poorly vascularized tumors in animal models respond as well as rapidly growing, highly vascularized tumors to therapy with the angiogenesis inhibitors TNP-470 and angiostatin.

Efficacy of antiangiogenic therapy with TNP-470 in superficial and invasive bladder cancer models in mice.

OBJECTIVES: To evaluate the efficacy of antiangiogenic therapy with O-(chloracetyl-carbamoyl) fumagillol (TNP-470) in a superficial and an invasive bladder cancer model in mice. The control of recurrent superficial and metastatic bladder cancer constitutes a major problem in urologic practice. Although the established therapies for these cases (immunotherapy, chemotherapy, and radiation therapy) have improved during the previous decades, further improvement and the reduction of existing side effects are needed. The inhibition of angiogenesis represents a new concept in cancer therapy. METHODS: We evaluated the in vitro effect of TNP-470 on the proliferation of bovine capillary endothelial cells (BCE), the superficial transitional cell carcinoma (TCC) cell line (KK-47), and the invasive TCC cell line (MGH-U1). To evaluate the in vivo effect of TNP-470 on the growth of advanced TCCs, both cell lines were injected subcutaneously into SCID mice. When tumors grew to a size of 100 to 200 mm(3), therapy either with TNP-470 or phosphate-buffered saline was initiated. RESULTS: TNP-470 strongly inhibited endothelial cell proliferation in vitro. The in vitro proliferation of both bladder carcinoma cell lines was also inhibited by TNP-470. However, the doses inhibitory to bladder carcinoma cells were 100-fold higher than the doses that were effective in the inhibition of endothelial cell proliferation. In vivo, TNP-470 significantly inhibited the growth of advanced KK-47 (67%) and MGH-U1 (68%) tumors in SCID mice. CONCLUSIONS: Our results indicate that antiangiogenic therapy with TNP-470 is equally effective in advanced superficial and invasive bladder carcinoma models in mice. When our results are taken together with the reports of other laboratories, TNP-470 appears to be a promising candidate as a tumor suppressor in superficial and invasive bladder cancer.

Serum levels of vascular endothelial growth factor and basic fibroblast growth factor in patients with soft-tissue sarcoma.

PURPOSE: Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) have been suggested to be important mediators for tumor-induced angiogenesis. We measured serum VEGF and bFGF levels from patients with soft-tissue sarcomas and correlated serum VEGF and bFGF levels with tumor status at surgery and histological grading. MATERIALS AND METHODS: A group of 18 healthy controls and 85 patients with soft-tissue sarcoma were enrolled in this study. The patients were classified according to tumor status at surgery. Serum levels of VEGF and bFGF were also correlated with histological grading. VEGF and bFGF levels were determined by enzyme-linked immunosorbent assay (Quantikine R&D Systems). RESULTS: Serum VEGF and bFGF levels were significantly elevated in the patient group (VEGF: 580pg/ml, bFbF: 21pg/ml, P = 0.0001). The highest concentrations of serum VEGF and bFGF were found in patients with macroscopic tumor lesions or G3 histology. Serum VEGF levels showed a statistically significant correlation with tumor status and grading (P = 0.006 for tumor status, P = 0.0001 for grading). CONCLUSIONS: This study reveals that elevated preoperative serum VEGF and bFGF levels can be detected in the majority of patients with soft-tissue sarcoma. The significant correlation with tumor mass and histological grading suggests that a consecutive monitoring of VEGF and bFGF in the serum of patients with soft-tissue sarcoma might be a valuable marker for tumor follow-up.

Laparoscopic vs open repair of gastric perforation and abdominal lavage of associated peritonitis in pigs.

BACKGROUND: Laparoscopy is increasingly used in conditions complicated by peritonitis, e.g., peptic ulcer perforation. Of some theoretical concern is the capnoperitoneum, which may aggravate peritonitis and induce septic shock due to increased intraabdominal pressure and distension of the peritoneum. This animal study was devised to analyze the effectiveness of laparoscopic versus traditional open repair of gastric perforation and abdominal lavage for associated peritonitis. METHODS: To simulate gastric perforation, female Duroc pigs were subjects to standardized gastrotomy. Either 6 or 12 h after gastric perforation, the animals underwent either traditional open or laparoscopic repair of the gastric defect and peritoneal lavage. The subjects were divided into the following four groups: peritonitis for 6 h and open surgery (group I) or laparoscopic surgery (group II); peritonitis for 12 h and open surgery (group III) or laparoscopic surgery (group IV). After an observation period of 6 days, the surviving animals were killed. The main outcome criteria were survival, perioperative changes of hemodynamics suggestive for septic shock, bacteremia, and endotoxemia. RESULTS: There were no significant differences between group I and II. Mortality was 22% in group III, as compared to 78% in group IV (p = 0.045). In group IV, the incidence of perioperative bacteremia and plasma endotoxin concentrations were significantly higher than in group III. Concomitantly, decreased mean arterial pressure and systemic vascular resistance, and increased cardiac output suggested a higher incidence of septic shock in group IV. CONCLUSION: Critical appraisal of laparoscopic surgery is warranted in conditions associated with severe, longstanding peritonitis.

Release of daunorubicin from polymethylmethacrylate for the improvement of the local growth control of bone metastasis animal experiments.

Bone metastases are a sign of advanced tumor disease. Surgical therapy is only occasionally curative. Therefore, the therapeutic goals are a limited surgical excision, immediate mobilization, effective stabilization and the avoidance of local recurrence. We investigated the effect of the anthracycline daunorubicin (DNR) in conjunction with polymethylmethacrylate (PMMA) in vitro and in animal experiments for regional control of bone metastases. Previous experiments of local chemotherapy in bone metastases using methotrexate (MTX) were done by Langendorff and Hernigou. In our own experiments we improved the release of daunorubicin from polymethylmethacrylate in vitro and in vivo up to 90% by adding mannitol. In in vivo experiments we investigated the combination of DNR and PMMA in athymic nude mice and Wistar rats. Cells from human breast cancer, bronchial carcinoma, nephroma, and soft tissue sarcoma were subcutaneously implanted bilaterally under the dorsal skin of nude mice. After reaching a diameter of 0.5 cm, the tumors were marginally excised, leaving microscopic tumor residuum behind. The tumor cavities were either filled with PMMA or alternatively with DNR-PMMA. The goal was to avoid tumor recurrence in the DNR-PMMA filled resection cavities. The number of recurrences was significantly lower in the DNR-PMMA treated animals, except in the breast cancer group. Additionally we implanted a rat sarcoma intrafemorally into Wistar rats. After 17 days the tumor was marginally excised and the resection cavity was filled with either DNR-PMMA or PMMA alone. The therapeutic goal was to prevent local recurrence. Histological and pharmacological tests concerning toxicity and drug distribution within the body completed the study. We concluded that the addition of daunorubicin to PMMA supplements surgical resection. We were able to reduce the number of, or delay recurrences in our animal models. Systemic side effects could be minimized despite the achievement of high local drug concentrations.

Toxic megacolon caused by cytomegalovirus colitis in a multiply injured patient.

Cytomegalovirus (CMV) colitis is a rare event that has been described mainly in immunocompromised patients with immunosuppressive medication or HIV infection. An association with severe trauma has not been described previously. We report a formerly healthy, multiply injured 75-year-old male who subsequently developed what appeared to be pseudomembranous colitis. By the time the diagnosis of toxic megacolon on the basis of CMV colitis was established, he had succumbed to multiple organ failure. Whenever pseudomembranous colitis is clinically suspected but not confirmed in a critically ill formerly healthy patient, CMV colitis should be excluded. Once the diagnosis is confirmed, generous resection of all affected colon is mandatory in view of the limited benefit of antiviral therapy in CMV-induced toxic megacolon.

Effect of a pneumoperitoneum on the extent and severity of peritonitis induced by gastric ulcer perforation in the rat.

Laparoscopic surgical repair of perforated gastroduodenal ulcer is technically feasible. To study the effect of a pneumoperitoneum on the extent and severity of peritonitis this animal study was devised. In rats gastric ulceration was induced by instillation of ethanol (50%, 2 ml) and followed by gastrotomy to simulate perforation. Animals were randomly allocated to pneumoperitoneum (PP) and control groups. In PP groups CO2 was insufflated intraperitoneally 6, 9, 12, and 24 h after gastrotomy. In controls the abdomen was only punctured. Animals were sacrificed 5 h after the end of PP or abdominal puncture. Blood cultures and intraabdominal swabs were assessed. A peritonitis severity score (PSS) based on histologies from peritoneum, liver, left kidney, spleen, and first jejunal loop was estimated. Six and 9 h after gastrotomy no significant differences between the PP and control groups were observed; 12 h after gastrotomy cultures of blood samples and abdominal swabs were positive in 67% and 75% in the PP group compared to 42% (P < 0.05), and 42% (P < 0.05) in controls. The mean PSS was 20.8 (standard deviation [SD] 2.2) in the PP group compared to 11.3 (1.5) (P < 0.01) in controls; 24 h after gastrotomy cultures of blood samples and abdominal swabs were positive in 83% and 100% in the PP group compared to 42% (P < 0.05) and 50% (P < 0.01) in controls. The mean PSS was 22.1 (1.5) in the PP group compared to 11.8 (2.4) (P < 0.01) in the controls.(ABSTRACT TRUNCATED AT 250 WORDS)

[Positive cytokeratin results in malignant melanoma. Pitfall in differential immunohistologic diagnosis of occult neoplasms]. / Zytokeratin-Positivität bei malignen Melanomen. Fallgrube bei der immunohistologischen Differentialdiagnose okkulter Neoplasien.

Immunohistology was performed on 84 paraffin-embedded surgical specimens of malignant melanomas (MM) from a total of 74 patients. The series consisted of 62 cutaneous primary tumors and 22 (partly selected) secondary manifestations (9 cutaneous recurrences and 13 metastases). In 4 patients with lymph node MM infiltrates, clinical investigations failed to identify a cutaneous primary tumor. In the primary and secondary manifestations respectively, the following proportions of immunohistologically positive cases were recorded: vimentin 100% each, S100-protein 95% each, NSE 87%/77%, HMB45 97%/64%, NKI/C3 97%/95%, cytokeratins (CK) (antibodies KL1, CAM5.2 and 35 beta H11) 0%/23%. Four of the 5 CK-positive lesions belonged to 3 patients in whom MM had occurred at first or exclusively as a lymph node infiltration. These findings confirm the results of other authors who report that positive staining results for CK can be expected in paraffin sections of secondary manifestations of MM in up to 10% of cases in large, nonselected series. This phenomenon appears, however, to be rare in primary cutaneous MM.

Immunocytochemistry in adrenocortical tumours: a clinicomorphological study of 72 neoplasms.

Surgical specimens of 72 adrenocortical tumours (ACTs) were investigated. Histologically, 57 tumours were classified as adenomas and 15 as carcinomas. In 9 of the latter cases, distant metastases and/or lethal outcome of disease was recorded. Immunocyto-chemistry showed only 2 ACTs to be positive for cytokeratin and 6 for vimentin. None of the 72 tumours showed argyrophilia or immunoreactivity for epithelial membrane antigen (EMA), S-100 protein, chromogranin A, Leu 7 or Leu-M1, while 31 cases exhibited positivity on immunostaining with a polyclonal antiserum against synaptophysin. All 72 ACTs were immunoreactive with the recently described antibody D11. Thus the panel of antibodies described here could not discriminate between adenomas and carcinomas or between carcinomas with aggressive and indolent behaviour. Immunostaining with D11 and for EMA and Leu-M1 may help to distinguish ACTs from phenotypically similar lesions of different histogenesis.

Immunocytochemistry of paragangliomas--value of staining for S-100 protein and glial fibrillary acid protein in diagnosis and prognosis.

Surgical specimens of 65 adrenal and 27 extra-adrenal paragangliomas, the latter comprising 11 carotid body, five jugulotympanic, one aorticopulmonary, eight aorticosympathetic and two visceral autonomic tumours, were examined immunocytochemically for the presence of glial fibrillary acid protein (GFAP) and S-100 protein. Six adrenal and four extra-adrenal (one parasympathetic and three sympathetic) neoplasms pursued a malignant clinical course. S-100 staining of sustentacular (type 2) cells was seen in both adrenal (48/65) and extra-adrenal (23/27) lesions, the 10 malignant tumours being entirely devoid of S-100 protein positive cells. GFAP positivity of type 2 cells was seen in only 16 of the extra-adrenal tumours, all of these lesions belonging to the group of benign parasympathetic paragangliomas. The presence of S-100 positive type 2 cells may thus help to exclude malignancy in individual paraganglioma cases, while GFAP positivity of such cells renders possible the correct typing of benign parasympathetic paragangliomas.

DNA cytophotometry in adrenocortical tumours: a clinicomorphological study of 66 cases.

Surgical specimens of 66 adrenocortical tumours were investigated by conventional microscopy and DNA cytophotometry. Histologically, 50 neoplasms were classified as adenomas and 16 as carcinomas. In only 8 of the latter cases were distant metastases and/or a lethal outcome recorded. On single cell scanning cytophotometry either non-euploid or aneuploid DNA histograms were identified in 24 of 50 adenomas (48%) and in 14 of 16 carcinomas (88%). The two carcinomas exhibiting euploid DNA distributions fell into the group of 7 malignancies which are recurrence-free so far. From these findings it is concluded that DNA measurements have no diagnostic and only limited prognostic value in neoplasms of the adrenal cortex.

Adrenomedullary hyperplasia and phaeochromocytoma. DNA cytophotometric findings in 47 cases.

Fifty adrenalectomy specimens containing normal (n = 3), hyperplastic (n = 4) or neoplastic (n = 43) medullary tissue were subjected to quantitative cytophotometric measurements of DNA content. Differing evaluation schemes were applied for interpretation of DNA distribution patterns. Of the 43 phaeochromocytomas (PCC), 16 were inherited as part of the syndrome of multiple endocrine neoplasia type 2a (MEN 2a). Five of 27 sporadic PCCs followed a malignant course. Three benign and three malignant PCCs lacked endocrine activity. In normal medulla and in adrenomedullary hyperplasia, diploid or euploid DNA distributions were found. In contrast, 87% (33/38) of the benign and all 5 malignant PCCs exhibited non-diploid or aneuploid DNA histograms. No differences in DNA content existed between functioning and non-functioning PCCs or between sporadic and hereditary tumours. In this study, in contrast to earlier communications, DNA cytophotometry did not discriminate between benign and malignant adrenomedullary tumours. In addition, as opposed to the findings in a variety of other endocrine tumours, DNA measurements did not appear to be a useful tool to assess the prognosis of an individual malignant PCC.