We report here two patients exhibiting a combination of falsely elevated serum levels of free thyroxine (FT4), free triiodothyronine (FT3), and thyrotropin receptor antibodies (TRAb), measured using Elecsys assay kits (Roche Diagnostics GmbH). The first patient was a 74-year-old man misdiagnosed with Graves' disease and treated with methimazole. The second patient was a 48-year-old woman whose serum FT4 and FT3 concentrations were found to be high during a blood test. These patients denied taking biotin or any other supplements. Further detailed examination, including a heterophilic blocking tube test, revealed the presence of serum antibodies. The abnormal reactions were observed only using the improved assay kits using ruthenium (Ru) sulfonate instead of Ru as a chemiluminescent agent. Therefore, serum antibodies to the Ru sulfonate complex caused the pseudo-high levels of FT4, FT3, and TRAb. To our knowledge, this is the first report showing that antibodies to the Ru sulfonate complex in the electrochemiluminescence immunoassay can cause falsely elevated levels of the combination, leading to discrepant thyroid function test results. We emphasize that in cases of abnormal test results, alternative assay methods should be considered for further examination; unusual test results should not be impulsively interpreted, even when using revised assay kits.
The surgical results for stage IVb gastric cancer remain very poor. The purpose of the current study is to reveal indications for paraaortic lymph node dissection in stage IVb gastric cancer patients with paraaortic lymph node involvement by analyzing prognostic factors for 3-year survival of stage IVb gastric cancer patients followed by curative B resection.The 3-year survival in clinicopathologic variables were compared by univariate analysis. Using Cox proportional hazards regression model, independent prognostic factors were identified from 11 variables.Overall 5-year survival in stage IVb was 26.5%; mean survival was 19 months. Using univariate analysis, p53 expression significantly influenced 3-year survival. Using Cox proportional hazards regression model, the number of total positive lymph nodes, the number of positive paraaortic lymph nodes, and p53 expression were independent prognostic factors.In stage IVb, paraaortic lymph node dissection should be indicated in patients with < or = 10 total positive lymph nodes, and < or = 3 positive paraaortic lymph nodes or p53 expression < or = 50%. This indication can be applied according to the preoperative imaging, the staining of p53 by endoscopic biopsy specimens and the intraoperative microscopic evaluation of dissected lymph nodes.
Linitis plastica, or Borrmann 4 gastric cancer, shows very poor prognosis, and the reason has not been understood. In the present study, we examined serum levels of trypsin(ogen) in 44 gastric cancer patients, including 17 early gastric cancer, 18 non-Borrmann 4 advanced gastric cancer, and 9 Borrmann 4 gastric cancer, by using the RIA gnost Trypsin kit (Hoechst Japan, Tokyo, Japan), which was expected to detect trypsin-1, trypsin-2, trypsinogen-1, and trypsinogen-2 in sera. The trypsin(ogen) concentration was much higher in the patients with linitis plastica than in the other gross types of gastric cancer. Hypertrypsinemia was identified in approximately 60% of advanced gastric cancer cases. Lymph node involvement, liver metastasis, or poorly differentiated adenocarcinoma is an important factor of hypertrypsinemia. The serum trypsin(ogen) level in linitis plastica patients was 3484.4 +/- 2319.7 ng/ml (mean +/- SD), which was significantly higher not only than that of the early gastric cancer (384.1 +/- 92.1) but also the stage IV gastric cancer patients (578 +/- 440.4), excluding those with linitis plastica. The elevated serum trypsinogen level in linitis plastica patients may be related to the malignant behavior of this type of cancer cell. Serum trypsin(ogen) of linitis plastica shows significantly higher concentrations than do the other types of advanced gastric cancer. Therefore, serum concentration of trypsin(ogen) might be a good marker of gastric cancer of linitis plastica.
Polymerase chain reaction (PCR) is a powerful tool for clinical diagnosis in the field of oncology, infection, and allergy. However, a simple and sensitive method for quantifying PCR products has not been established. We therefore used a novel fluorescence DNA intercalator, pyrylium iodide (P2) to quantify PCR products. A 838-bp fragment of the human beta-actin gene and a 374-bp fragment of the gene for ornithine decarboxylase (ODC) and ODC primer dimers were generated by PCR and quantified using either P2 or another fluorescence DNA intercalator, YOYO-1. In addition, utilizing RT-PCR and the P2 method, the ODC mRNA expression from 10 colonic cancers was quantified. Serially diluted beta-actin and ODC PCR products could be quantified using P2 without having to separate them from primer dimers and other components of the reaction mixture. However, YOYO-1 could not be used to quantify the PCR products because of high background fluorescence from the primer dimers. In the clinical study, ODC mRNA expression as quantified by P2 was significantly higher in cancerous tissue (113.8 +/- 4.1; mean +/- SEM; plate reader units) than in mucosa of normal appearance (68.4 +/- 4.8). P2 is a promising tool for quantifying PCR products.
Since surgical results in advanced gastric cancer remain poor and para-aortic lymph node dissection may contribute to survival, it is useful to determine the significance of para-aortic lymph node dissection.Para-aortic lymph node dissection was provisionally indicated for patients with invasion depth deeper than the subserosal layer. Clinicopathologic variables were retrospectively analyzed using univariate analysis and multivariate analysis to predict para-aortic lymph node metastasis. Similarly, they were analyzed using univariate analysis and the Cox's proportional hazards regression model to estimate the prognostic factor in 120 patients who underwent para-aortic lymph node dissection. Surgical results and post-operative complications were compared between para-aortic lymph node dissection and D2 dissection.Univariate analysis revealed that the mean diameter, the degree of lymph node metastasis, and the invasion depth were significant predictors of para-aortic lymph node metastasis. Multivariate analysis showed that n2 was the only independent predictive factor as to para-aortic lymph node metastasis. Univariate analysis revealed tumor site, tumor diameter, lymph node metastasis, number of positive lymph nodes, INF, and stage were significantly associated with 5-year survival. The Cox's proportional hazards regression model showed that the number of positive lymph nodes and the number of positive para-aortic lymph nodes were independent prognostic factors. Patients with < or = 10 positive lymph nodes in any stage or < or = 3 positive para-aortic lymph nodes in stage IVb had significantly better surgical results. Surgical results for patients who underwent para-aortic lymph node dissection with n2 or invasion depth deeper than the exposed serosa were significantly higher than those in D2. As to post-operative complications, pancreatic fistula and respiratory complications were significantly frequent after para-aortic lymph node dissection.n2 is helpful in predicting para-aortic lymph node metastasis. Whereas, post-operative morbidity such as pancreatic fistula and respiratory complications after para-aortic lymph node dissection were significantly higher, they were controllable. Para-aortic lymph node dissection should be indicated in advanced gastric cancer patients in which lymph node metastasis is over n2 or invasion depth is deeper than the exposed serosa. But the number of positive para-aortic lymph nodes must be less than three.
We analyzed the relationship between clinical response to neo-adjuvant chemotherapy including 5-fluorouracil (5-FU) in patients with hypopharyngeal carcinoma (HPC) and thymidylate synthase (TS) expression in their tumors. TS expression was evaluated with immunohistochemical staining techniques on biopsy specimens from HPC patients. TS immunostaining was divided into four levels (TS0-TS3) according to its level and pattern. The relationship between prognosis, tumor size, nodal status, differentiation of tumor cells and TS expression were also investigated. There was a statistically significant association between the level of TS expression and tumor size (p < 0.01). In terms of the effectiveness of chemotherapy, tumor differentiation, nodal status and prognosis, a statistical difference was not found in TS expression. These results suggest that the level of TS expression may show the degree of tumor proliferation, but may not necessarily be useful to obtain a response to chemotherapy including other drugs, e.g., cisplatin and other derivatives of platinum.
OBJECTIVE Our goal was to ascertain the prevalence of pruritus in diabetic and nondiabetic subjects and the relevance of symptoms, signs, and nerve functions of diabetic polyneuropathy (DPN) of pruritus. RESEARCH DESIGN AND METHODS A large-scale survey of 2,656 diabetic outpatients and 499 nondiabetic subjects was performed. In diabetic subjects, the relationship between pruritus and age, sex, diabetic duration, A1C, Achilles tendon reflex (ATR), and abnormal sensation in legs was evaluated. In 105 diabetic subjects, nerve conduction studies, quantitative vibratory threshold (QVT), heart rate variability, and a fall of systolic blood pressure at a head-up tilt test (ΔBP) were performed, and the relationships between pruritus and nerve functions were evaluated. RESULTS Although the prevalence of truncal pruritus of unknown origin (TPUO) in diabetic subjects was significantly higher than that in age-matched nondiabetic subjects (11.3 vs. 2.9%, P = 0.0001), the prevalence of other pruritus was not different between the two groups. Multiple logistic regression analysis revealed that abnormal sensation and ATR areflexia were independent risk factors for TPUO in age, sex, duration of diabetes, and A1C. ΔBP in diabetic subjects with TPUO was significantly impaired compared with that in those without TPUO. Larger ΔBP was identified as a significant risk factor of TPUO independent of other nerve dysfunctions by multiple logistic regression analysis. CONCLUSIONS TPUO is significantly more frequent in diabetic than in nondiabetic individuals. TPUO is significantly associated with symptoms and signs of DPN, including impaired blood pressure response in a head-up tilt test. TPUO, therefore, might be a newly recognized symptom of DPN.
