Detection of occult lymph node metastases in esophageal cancer by minimally invasive staging combined with molecular diagnostic techniques.
BACKGROUND AND OBJECTIVES: Lymph node metastases are the most important prognostic factor in patients with esophageal cancer. Histologic examination misses micrometastases in up to 20% of lymph nodes evaluated. In addition, non-invasive imaging modalities are not sensitive enough to detect small lymph nodes metastases. The objective of this study was to investigate the use of reverse transcriptase-polymerase chain reaction (RT-PCR) of messenger RNA (mRNA) for carcinoembryonic antigen (CEA) to increase the detection of micrometastases in lymph nodes from patients with esophageal cancer. METHODS: RT-PCR of CEA mRNA was performed in lymph nodes from patients with malignant and benign esophageal disease. Each specimen was examined histopathologically and by RT-PCR and the results were compared. RESULTS: Metastases were present in 29 of 60 (48%) lymph nodes sample by minimally invasive staging from 13 patients with esophageal cancer when examined histopathologically. RT-PCR identified nodal metastases in 46 of these 60 (77%) samples. RT-PCR detected CEA mRNA in all 29 histologically positive samples and in 17 histologically negative lymph nodes. All lymph nodes from patients with benign disease (n = 15) were negative both histopathologically and by RT-PCR. The stage of two patients was reclassified based on the RT-PCR results, which identified lymph node spread undetected histopathologically. Both of these patients developed recurrent disease after resection of the primary tumor. CONCLUSIONS: RT-PCR is more sensitive than histologic examination in the detection of lymph node metastases in esophageal cancer and can lead to diagnosis of a more advanced stage in some patients. The combination of minimally invasive surgical techniques in combination with new molecular diagnostic techniques may improve our ability to stage cancer patients. (+info)
Medullary thyroid carcinoma with multiple hepatic metastases: treatment with transcatheter arterial embolization and percutaneous ethanol injection.
A 54-year-old man with medullary thyroid carcinoma in the thyroid gland was unable to undergo total thyroidectomy because the tumor had invaded the mediastinum. Radiation therapy and chemotherapy were given. Seven years later, intractable diarrhea and abdominal pain appeared, and computed tomography demonstrated hypervascular tumors in the thyroid gland and in the liver. The tumors were successfully treated with percutaneous ethanol injection to a lesion in the thyroid gland and transcatheter arterial embolization followed by percutaneous ethanol injection to tumors in the liver. Transcatheter arterial embolization and percutaneous ethanol injection may be valuable in treating medullary thyroid carcinoma. (+info)
The intrarenal vascular lesions associated with primary antiphospholipid syndrome.
Even 10 yr after the identification of the antiphospholipid syndrome (APS), renal involvement in the course of APS is still relatively unrecognized, and is probably underestimated. The association of anticardiolipin antibodies and/or lupus anticoagulant with the development of a vaso-occlusive process involving numerous organs is now confirmed. In a multicenter study, 16 cases of "primary" APS (PAPS) were found and followed for 5 yr or more, all with renal biopsy. In all 16 cases of PAPS, there was a vascular nephropathy characterized by small vessel vaso-occlusive lesions associated with fibrous intimal hyperplasia of interlobular arteries (12 patients), recanalizing thrombi in arteries and arterioles (six patients), and focal cortical atrophy (10 patients). In combination, these led to progressive destruction of the kidney, accelerated by acute glomerular and arteriolar microangiopathy in five patients. Focal cortical atrophy is a distinctive lesion, present in 10 biopsies, and likely represents the histologic and functional renal analogue to the multiple cerebral infarcts detected on imaging studies. The clinical hallmark of this vascular nephropathy in PAPS is systemic hypertension, only variably associated with renal insufficiency, proteinuria, or hematuria. The ensemble of histologic renal lesions defined in this study should aid in the separation of the lesions found in cases of secondary APS, especially systemic lupus erythematosus, into those lesions related to APS and those related to the underlying disease. (+info)
Nodular glomerulosclerosis with deposition of monoclonal immunoglobulin heavy chains lacking C(H)1.
The objective of this study was to further characterize the clinical and immunopathologic features of heavy chain deposition disease (HCDD), a recently described entity. Four patients were diagnosed as having HCDD on a kidney biopsy. All presented with nodular glomerulosclerosis with deposition of gamma1 heavy chains lacking CH1 epitopes, but without light chains. Two different patterns were observed in the serum. First, patients 1 and 2 had a circulating monoclonal IgGlambda containing a short gamma1 heavy chain lacking CH1 epitopes, with an apparent molecular weight of 40 kD consistent with a complete CH1 deletion. Biosynthetic experiments also showed that the deleted heavy chain was produced in excess compared with light chains, and was secreted in vitro together with half Ig molecules, although these abnormal components were not detected by Western blot analysis of whole serum. Second, patients 3 and 4 had a circulating monoclonal IgG1lambda with an apparently normal, nondeleted heavy chain subunit, but serum fractionation followed by immunoblotting revealed an isolated monoclonal gamma1 chain lacking CH1 epitopes. These data strongly suggest that renal deposition of a CH1-deleted heavy chain circulating in low amounts in the serum as a free unassembled subunit is a major feature of HCDD. The CH1 deletion is most likely responsible for the premature secretion in blood of the heavy chain by a clone of plasma cells. (+info)
Angiotensin II receptor type 1 gene expression in human glomerulonephritis and diabetes mellitus.
The renin-angiotensin system plays an important role in the progression of chronic renal disease. Although the expression of renin and angiotensin-converting enzyme in experimental and human renal disease has been well characterized, no information is available regarding human angiotensin type 1 (AT1) receptor expression. The net effect of renin depends on AT1 receptor expression, among other factors. Receptor expression was determined in renal biopsy samples (including all tissue components) and isolated glomeruli from patients with glomerulonephritis (GN) or diabetic nephropathy (non-insulin-dependent diabetes mellitus). Biopsy samples and isolated glomeruli from tumor-free tissue from tumor nephrectomies served as controls. Human AT1 receptor gene expression was determined by quantitative reverse transcription-PCR, using an AT1 receptor deletion mutant as the internal standard. In whole biopsy samples from 37 patients with various types of GN, AT1 receptor mRNA levels were lower, compared with nine control biopsy samples (P < 0.001). AT1 receptor mRNA levels were also significantly lower (P < 0.001) in eight samples from patients with diabetic nephropathy. In microdissected glomeruli, AT1 receptor gene expression was significantly lower in samples from patients (n = 22) with various types of GN, compared with 12 microdissected tumor nephrectomy control samples (P < 0.0023). It is concluded that AT1 receptor mRNA expression is low in glomeruli of patients with chronic renal disease. This may reflect a regulatory response to (inappropriately) high intrarenal angiotensin II concentrations. (+info)
Bone marrow scintigraphy using technetium-99m antigranulocyte antibody in malignant lymphomas.
BACKGROUND: The purpose of this study was to elucidate the clinical reliability of immunoscintigraphy (IS) to detect infiltration of the bone marrow in patients with malignant lymphoma. PATIENTS AND METHODS: Whole body IS was performed in 103 patients with Hodgkin's disease (HD) or non-Hodgkin's lymphoma (NHL) using Tc-99m labelled anti-NCA-95 which allows visualization of the granulopoietic bone marrow. Of these, 52% were studied prior to any therapy. Findings were compared to posterior iliac crest biopsy as well as MRI and/or follow-up examination. Criteria of marrow infiltration were a positive biopsy, positive follow-up, or positive results of MRI. RESULTS: Comparison of IS and biospy revealed concordant findings in 69 and discordant findings in 34 of 103 patients. Of the 34 patients with discordant results, IS showed lesions suspicious of bone marrow infiltration in 29 patients despite normal biopsy findings. When follow-up and additional examinations were taken into consideration, 10 patients remained with probably false positive and five with false negative IS findings. IS proved to be highly sensitive and specific in patients with HD (100% and 84%, respectively) and high-grade NHL (93% and 84%, respectively). Moderate sensitivity (60%) was found in low-grade NHL. This was possibly due to false negative IS in three to five patients with chemotherapy in contrast to one of five false negative results in patients without chemotherapy. CONCLUSION: Bone marrow scintigraphy using antigranulocyte antibodies is highly sensitive in HD and high-grade NHL. Positive findings in IS subsequent to a negative biopsy should be followed by guided re-biopsy or MRI. (+info)
Benzodiazepine premedication: can it improve outcome in patients undergoing breast biopsy procedures?
BACKGROUND: Women awaiting needle-guided breast biopsy procedures may experience high anxiety levels. A randomized, double-blind, placebo-controlled study was designed to evaluate the ability of midazolam and diazepam (in a lipid emulsion [Dizac]) to improve patient comfort during needle localization and breast biopsy procedures. METHODS: Ninety women received two consecutive doses of a study medication, one before the mammographic needle localization and a second before entering the operating room. Patients were assigned randomly to receive saline, 2.0 ml intravenously, at the two time points; midazolam, 1.0 mg intravenously and 2.0 mg intravenously; or diazepam emulsion, 2.0 mg intravenously and 5.0 mg intravenously, respectively. Patients assessed their anxiety levels before the needle localization, before entering the operating room, and on arrival in the operating room. Patients completed a questionnaire evaluating their perioperative experience at the time of discharge. RESULTS: Patient satisfaction during needle localization was significantly improved in both benzodiazepine treatment groups (vs. saline). The incidence of moderate-to-severe discomfort during needle localization was lower in the midazolam (20%) and diazepam emulsion (6%) groups compared with the saline group (70%) (P<0.05). The preoperative visual analogue scale anxiety scores were similar in all three groups. In the operating room, however, anxiety scores were 55% and 68% lower after midazolam (21+/-19) and diazepam emulsion (15+/-14) compared with saline (46+/-28). Finally, there was no difference in the time to achieve home-readiness or actual discharge time among the three groups. CONCLUSIONS: Premedication with midazolam or diazepam emulsion improved patients' comfort during needle localization procedures and significantly reduced intraoperative anxiety levels before breast biopsy procedures without prolonging discharge times. Use of diazepam emulsion may be an effective alternative to midazolam in this population. (+info)
Evaluation of "solitary" thyroid nodules in a community practice: a managed care approach.
Evaluation of thyroid nodules remains a challenge for primary care physicians. To include or exclude the presence of malignancy in a thyroid nodule, radioisotope scan, ultrasound, and fine-needle aspiration biopsy of the thyroid generally are used. The objectives of this study were to determine the utility and cost effectiveness of fine-needle aspiration biopsy of solitary thyroid nodules in a community setting; to compare the cost of fine-needle aspiration biopsy with that of radioisotope scan and ultrasound; and to determine whether the practice of obtaining radioisotope scans and ultrasound has changed in the 1990s compared with the 1980s. Patients were referred by community physicians to university-based endocrinologists for evaluation of thyroid nodules. Many of the patients had previously undergone radioisotope scans and ultrasound scans at the discretion of their primary care physicians. All patients underwent fine-needle aspiration biopsy. The biopsy results were evaluated prospectively, and the practice of community physicians' obtaining radioisotope scans and ultrasound scans was compared for the 1980s and 1990s. Eighty-three patients underwent 104 biopsies. In 20 biopsies the specimens were inadequate; the others showed 70 benign, 9 suspicious, and 4 malignant lesions. All four patients with biopsy findings read as malignant were found to have malignant growth at surgical procedures. Two benign biopsy findings were false-negative results. Malignant growth was correctly diagnosed later for one patient at a second biopsy and for the other because of growth of the nodule. The cost of 104 biopsies was $20,800. The cost of radioisotope scans was $22,400, and the cost of ultrasound scans was $10,640. The frequency of obtaining radioisotope scans (84.5% vs 77%) and ultrasound scans (65% vs 45%) was slightly higher in the 1990s compared with the 1980s. Fine-needle aspiration biopsy is a safe and cost effective initial evaluation modality for smaller community-based centers, as it is at large tertiary centers. The cost incurred ($33,040) in obtaining the radioisotope scans and ultrasound scans could have been saved if fine-needle aspiration biopsy had been used as the initial diagnostic procedure for evaluation of these nodules. Although radioisotope scan and ultrasound scan are of little diagnostic help in the evaluation of thyroid nodules, they continued to be obtained at a high frequency during the last decade. (+info)