Laparoscopic management of gastrointestinal stromal tumors.

BACKGROUND: Surgery remains the standard for nonmetastatic gastrointestinal stromal tumors (GISTs). Laparoscopic surgery should be considered for these tumors as their biologic behavior lends them to curative resection without requiring large margins or extensive lymphadenectomies. METHODS: A retrospective review was performed of patients who underwent laparoscopic treatment of GISTs by surgeons at the Mount Sinai Medical Center from 2000-2005. Records were reviewed with respect to patient demographics, medical history, diagnostic workup, operative details, postoperative course, and pathologic characteristics. RESULTS: Laparoscopic surgery was attempted in 43 patients with GISTs. The average age was 65 years and 21 were women. Fifty-six percent of patients presented with anemia or gastrointestinal bleeding. The tumors were located in the stomach (65%) and in the small bowel (35%). The mean tumor sizes were 4.6 cm (stomach) and 3.7 cm (small bowel). Gastric operations included laparoscopic wedge (29%), sleeve (21%), and partial (29%) gastrectomies. The three gastric conversions were due to local invasion of tumor into adjacent organs or proximity to the gastroesophageal junction. Small bowel operations included laparoscopic resections with extracorporeal (47%) and intracorporeal anastamoses (33%). Conversion in small bowel operations was associated with coincidental pathology in addition to the GIST. This consisted of an associated bowel perforation and a synchronous colonic carcinoma. There was one mortality and a 9% morbidity rate, including an evisceration requiring reoperation. All tumors were pathologically confirmed with CD117 immunohistochemistry. CONCLUSIONS: In light of their biologic behavior, GISTs should be considered for laparoscopic resection. This minimally invasive approach to these tumors can be performed safely and reliably.

Pulmonary metastatic leiomyosarcoma coexisting with pulmonary chondroma in Carney's triad.

The diagnosis of Carney's triad requires the coexistence of at least two of three rare disorders, including gastric epithelioid leiomyosarcoma, pulmonary chondroma, and functioning extra-adrenal paraganglioma. Seventeen cases have been reported so far, occurring predominantly in young female patients. We report herein the 18th case of this entity and the first case, to our knowledge, where pulmonary metastases from a gastric leiomyosarcoma coexisted in a patient with benign pulmonary chondromas.

Amyloidosis and inflammatory bowel disease. A 50-year experience with 25 patients.

Amyloidosis is a rare but serious complication of inflammatory bowel disease (IBD), especially Crohn's disease (CD). It occurred in 15 of our 1709 patients with CD (0.9%) (706 with ileocolitis, 310 with colitis, and 693 with enteritis), but in only 1 of our 1341 patients with ulcerative colitis (UC) (0.07%), admitted to The Mount Sinai Hospital between 1960 and 1985. Eleven of the patients with CD who had amyloidosis had ileocolitis, 2 colitis, and 2 ileitis; these figures represent a frequency within each group of 1.6%, 0.6%, and 0.3%, respectively. Amyloidosis was thus associated 4.4 times more often with CD of the colon than with pure small bowel disease. We have added to this group of 15 patients the 5 cases of CD that were originally reported by Werther et al in 1960, plus another 4 (2 with UC and 2 with CD) who have been seen since 1985, making a total of 25 patients in this series, 22 with CD and 3 with UC. There was a striking male preponderance, 16 of 22, among patients with CD, although 2 of the 3 patients with UC were female. Amyloid disease was diagnosed at a mean age of 40 years, 15 years (range, 1-42) after the onset of CD. Six major forms of amyloidosis occurred: nephropathy, enteropathy, cardiomyopathy, hepatosplenomegaly, thyroid mass, and generalized amyloidosis. Renal disease with proteinurea and/or renal insufficiency occurred in 18 of the 22 patients with CD and in all 3 with UC. Nephropathy was by far the most common lethal manifestation of IBD-associated amyloidosis in this series. Nephrotic syndrome developed in 15 patients with CD and was accompanied by renal failure, the major contributor to mortality, in 10 of the 13 patients who died. Amyloidosis may be associated with suppurative or other extraintestinal manifestations of IBD. Fifteen of the 22 patients with CD who had amyloidosis also had suppurative complications of their bowel disease, although the other 7 had no recognizable suppuration. Extraintestinal manifestations were also common in this series, occurring in 12 of 22 patients with CD and in 2 of the 3 patients with UC; 6 of the 18 patients with nephrotic syndrome also had arthritis. However, there is no evidence that patients with IBD with amyloidosis have extraintestinal manifestations more frequently than do IBD patients without amyloidosis. Earlier reports of amyloid associated with IBD came from autopsy series. In recent years, biopsy has allowed diagnosis to be made during life.(ABSTRACT TRUNCATED AT 400 WORDS)

Resolution of renal amyloidosis.

A patient with renal amyloidosis and the nephrotic syndrome consequent to extensive infected burns demonstrated both clinical resolution of the nephrotic syndrome and morphologic regression of the renal amyloid deposits over a six year period. The regression of the amyloid deposits was associated with several changes in the glomerular capillary wall resulting in a double capillary wall contour. This case indicates that deposits of amyloid in the kidney may regress and suggests a sequence of events in this resolution.

Fatal disseminated adenovirus 11 pneumonia in an agammaglobulinemic patient.

Adenovirus type 11, an organism not previously associated with pneumonia, caused the death of a patient with infantile x-linked agammaglobulinemia who had normal cell-mediated immunity. Despite long-standing, regular therapy with immune globulin, his serum lacked neutralizing antibody to the virus. This case confronts the conventional view that viral infections are primarily resisted by cellular immune reactions and reemphasizes the importance of antibody in the host defense against adenoviruses. It further demonstrates the continued vulnerability of such patients to certain pathogens in the presence of presumably adequate standard-dose passive immunization.

Small bowel transplantation in the rat. Effect of pretransplant blood transfusions and cyclosporine on host survival.

We investigated the effect of pretransplant conditioning as a way to reduce the need for the aggressive immunosuppressive therapy reportedly required in small bowel (SB) allograft recipients. LEW rats were conditioned with (1) a donor-specific blood transfusion (DST) on day -8 and a concurrent 5-day course of CsA (10 mg/kg/day); (2) a nonspecific blood transfusion and CsA; (3) CsA alone. A 10-cm segment of the host native bowel was then replaced with an equivalent segment of SB obtained from ACI rats. Postoperative treatment consisted of CsA at 2.5 mg/kg/day for 30 days. Rats conditioned with a nonspecific transfusion and CsA or with CsA alone survived for 14.1 +/- 5.8 and 18.3 +/- 5.7 days, respectively. In contrast, rats conditioned with DST and CsA survived for 60.3 +/- 36.2 days (P less than 0.001 vs. both controls). Biopsies taken from long-term survivors showed a normal bowel architecture. The function of the allografts was studied in a group of animals totally deprived of their native bowel and transplanted with a 30-cm segment of ACI SB. CsA-DST-treated recipients survived an average of 90 +/- 43 days and grew at a rate comparable to isografted animals. Treated allograft recipients had maltose absorption indistinguishable from isografted controls at all times tested. In contrast, maltose absorption was severely impaired in recipients rejecting their grafts. This study demonstrates that long-term survival of SB allograft recipients can be achieved with good functional results with low doses of CsA in recipients conditioned with DST and CsA.

Nucleolar localization of BRCA1 protein in human breast cancer.

Both a rabbit polyclonal BRCA1 antibody, K-18, and a mouse monoclonal BRCA1 antibody, AP 16, produced nucleolar epithelial cell staining on frozen tissue sections of human infiltrating mammary carcinomas. There was much less BRCA1 antibody staining in normal tissues; however, 2 intraductal tumors and a papilloma, found in proximity to the carcinomas showed considerable nucleolar immunoreactivity. MCF-7 cells fixed in methanol and immunostained with the same two antibodies also revealed nucleolar staining, however, after 4% paraformaldehyde fixation for three minutes, there were many fewer nuclei stained. Antigen retrieval methods on formalin-fixed, paraffin-embedded specimens produced tumor cell cytoplasmic staining with AP 16 and nuclear staining in both tumor and normal epithelial cells with another BRCA1 monoclonal antibody, SG 11.

Morphologic and clinical correlates in renal amyloidosis.

Morphologic studies and clinical correlations were undertaken in 59 patients with renal amyloidosis. Spicularly arranged amyloid deposits in the glomerular capillary wall were found in all clinical groups but were more frequent and more extensive in primary amyloidosis and multiple myeloma. The severity of proteinuria correlated with the presence of spicules and podocyte destruction rather than with the amount of amyloid in the glomerulus. The spicules were associated with morphologic and clinical evidence of rapid amyloid deposition and a fulminant clinical course. The absence of spicules and the presence of extensive new basement membrane material may produce basement membrane thickening, lamination, and double capillary wall contours, which are associated with mild proteinuria and, rarely, resolution of amyloidosis. Nodular or mixed nodular-diffuse patterns of glomerular amyloid deposits were more frequent in patients with secondary amyloidosis and a longer clinical course. Renal failure generally corresponded to severe glomerular amyloidosis and tubular atrophy. However, a relatively precipitous, usually irreversible decrease in renal function frequently occurred in patients with renal amyloidosis and did not always have a morphologic explanation. The duration of life from the time of biopsy no death in patients with primary amyloidosis (nine months) was markedly shorter than in those with secondary amyloidosis (more than 50 months).

Morphometric analysis of glomerular basement membranes (GBM) in thin basement membrane disease (TBMD).

We measured the thickness of glomerular basement membrane in 46 patients with thin basement membrane disease (TBMD), (age range 15-50 years, almost equal M:F ratio), and compared with that in a control group of 5 patients (age range 5-38 years) with normal glomerular morphology. The measurements of glomerular basement membrane taken from electron micrographs (magnification x 12,500) were analyzed using an interactive image analysis system assembled around an INTEL 10 microcomputer, with a high resolution touch sensitive screen as the interactive peripheral. Calculation was done by printing on an electron micrograph a grating replica (21,600 lines/cm), with the same magnification as the electron micrographs of the glomeruli and calibrating the arithmetic (AM) and harmonic (HM) mean for each case. Comparing the results of TBMD cases (AM 129-202 nm; HM 128-213 nm) with those of the control group consisting of 5 cases of "minimal change nephrotic syndrome" (AM 287-317 nm; HM 300-333 nm) it was found that GBM in TBMD is remarkably thin. The thinning was caused mainly by the decreased width of the lamina densa (TBMD group: 71.4-147.0 nm; HM 72.4-154.4 nm in comparison with the control group: AM 174.4-235.5 nm; HM 184.2-249.6 nm). This finding allows us to differentiate thin basement membrane disease from other glomerulopathies presenting primarily with isolated or recurrent hematuria.

Lipid degeneration in a pheochromocytoma histologically mimicking an adrenal cortical tumor.

A recurrent adrenal pheochromocytoma is reported in an 18-year-old woman with a family history of multiple endocrine neoplasia type IIA. The tumor was noteworthy for the presence of numerous fine intracytoplasmic lipid droplets confirmed by fat stain. Immunohistochemical studies revealed cytoplasmic positivity for chromogranin and neuron-specific enolase typical of pheochromocytoma. Electron microscopy demonstrated dense-core neurosecretory granules, in addition to the cytoplasmic lipid vacuoles. The presence of lipid within an adrenal pheochromocytoma is rare and, to our knowledge, has been documented in only one previous case report in the literature.

Amyloidosis. An unusual complication of Gaucher's disease.

Gaucher's disease has been associated with plasma cell dyscrasias. A patient had Gaucher's disease, nephrotic syndrome, and systemic amyloidosis. Plasmacytosis in the bone marrow, the presence of light chains in the urine and renal glomeruli, and the finding of low circulating immunoglobulin levels suggest that the amyloid in this patient is related to a plasma cell dyscrasia.

Paragangliomatosis associated with multiple endocrine adenomas.

A 19-year-old woman had multiple functioning extra-adrenal paragangliomas, a pituitary adenoma associated with acromegaly, parathyroid hyperplasia, and pigmentary abnormalities. This case differs from previously described instances of multiple endocrine adenomatosis (MEA) and has features that bridge the classic MEA type 1 and 2 syndromes and possibly Von Recklinghausen disease. The coexistence of pheochromocytoma with acromegaly is extremely rare, and the association with extra-adrenal paragangiliomas appears to be unique. Thyroid parafollicular cell proliferation could not be proved by immunohistochemical or electron microscopical studies. The large number and extensive distribution of paragangliomas, ranging from neck to pelvis, is another unique feature of this case. The concept of neurocrestopathy or of an endocrine polypeptide (APUD) cell system may offer an explanation for the interrelation of these diverse growths.

Unilateral glomerulonephritis.

Three patients had unilateral glomerulonephritis. In two, the protected kidney was associated with stenosis of its renal artery, and in the third patient, a hydronephrotic kidney was spared. These clinical examples of unilateral glomerulonephritis and similar experimental models illustrate the effect of hemodynamic and hydrostatic influence in the manifestation of glomerulonephritis. Glomerulonephritis associated with unilateral arterial or ureteral disease may cause clinical confusion and error in diagnosis and treatment.

Asbestosis, endobronchial Aspergillus infection, and bronchocentric granulomatosis presenting with hemoptysis.

A patient with pulmonary asbestosis developed hemoptysis and a lesion on chest radiograph secondary to bronchocentric granulomatosis (BG) associated with Aspergillus fumigatus. Although pulmonary Aspergillus infection is a known complication of asbestos exposure. BG has not been previously reported in this disorder. This patient's case further documents that Aspergillus hyphae may be present in BG unassociated with allergic bronchopulmonary aspergillosis. A wide range of processes affecting airways, including asbestos exposure, may be associated with bronchocentric granulomatosis.

Mediastinal carcinoid with an incomplete Sipple's syndrome.

A 60-year-old woman with a mediastinal carcinoid of probable thymic origin, widely metastatic, had associated parathyroid hyperplasia, medullary carcinoma of thyroid with amyloid stroma and an adrenal neuroma. This case demonstrated features of an incomplete Sipple's syndrome (MEA II). The relationship of these diverse tumors is consistent with the concept of the APUD system and neurocristopathies.

Carcinoma of the colon in asbestos-exposed workers: analysis of asbestos content in colon tissue.

Epidemiological studies have indicated an increased incidence of carcinoma of the colon in asbestos workers. The present study evaluated the colon tissue asbestos burden, by light and electron microscopic analytic techniques, in patients with a history of occupational asbestos exposure and colon cancer. Asbestos fibers and/or asbestos bodies were present in colon tissue from 14 of 44 (31.8%) asbestos workers with colon carcinoma (range 142,199 to 15,231, 543 fibers/g/wet weight, mean 2,517,823). Chrysotile was identified in 9 patients and amosite in 3 patients. Both amosite and chrysotile were found in the colonic wall in one individual. Other forms of asbestos (e.g., crocidolite, tremolite, or anthophyllite) were not found. Asbestos fibers and asbestos bodies were not found in colon tissue from 20 control patients (colon carcinoma and no asbestos exposure). Asbestos fibers frequently enter and reside in the wall of the colon and are often intimately associated with tumor tissue at the site of colon carcinoma in workers with asbestos exposure and colon carcinoma.