Effectiveness of administering zinc acetate hydrate to patients with inflammatory bowel disease and zinc deficiency: a retrospective observational two-center study.

BACKGROUND/AIMS: Inflammatory bowel disease (IBD) patients frequently have zinc deficiency. IBD patients with zinc deficiency have higher risks of IBD-related hospitalization, complications, and requiring surgery. This study aimed to examine the effectiveness of zinc acetate hydrate (ZAH; Nobelzin) in IBD patients with zinc deficiency. METHODS: IBD patients with zinc deficiency who received ZAH from March 2017 to April 2020 were registered in this 2-center, retrospective, observational study. Changes in serum zinc levels and disease activity (Crohn's Disease Activity Index [CDAI]) before and after ZAH administration were analyzed. RESULTS: Fifty-one patients with Crohn's disease (CD, n = 40) or ulcerative colitis (UC, n = 11) were registered. Median serum zinc level and median CDAI scores significantly improved (55.5-91.0 µg/dL, P< 0.001; 171.5-129, P< 0.001, respectively) in CD patients 4 weeks after starting ZAH administration. Similarly, median serum zinc levels and CDAI scores significantly improved (57.0-81.0 µg/dL, P< 0.001; 177-148, P= 0.012, respectively) 20 weeks after starting ZAH administration. Similar investigations were conducted in groups where no treatment change, other than ZAH administration, was implemented; significant improvements were observed in both serum zinc level and CDAI scores. Median serum zinc levels in UC patients 4 weeks after starting ZAH administration significantly improved from 63.0 to 94.0 µg/dL (P= 0.002), but no significant changes in disease activity were observed. One patient experienced side effects of abdominal discomfort and nausea. CONCLUSIONS: ZAH administration is effective in improving zinc deficiency and may contribute to improving disease activity in IBD.

Histoculture drug response assay predicts the postoperative prognosis of patients with esophageal cancer.

Predicting response to chemotherapy would provide patients suffering from malignant tumor with not only more favorable outcomes, but also reduction of adverse events, and would enable chemotherapy tailored to individual patients. The purpose of this retrospective study was to evaluate the utility of histoculture drug response assay (HDRA) with the MTT endpoint. Subjects comprised 53 consecutive patients diagnosed with esophageal cancer, with 15 patients receiving preoperative chemoradiotherapy (CRT) followed by surgery (CRT group; n=15) and 38 patients undergoing surgery (surgery group; n=38), including 17 patients with histological lymph node metastasis who received postoperative chemotherapy. Tumor samples obtained from patients were used for HDRA with MTT endpoint and correlations of sensitivity from HDRA with MTT endpoint to clinical response to preoperative CRT, accuracy of in vitro sensitivity test, and clinical outcomes based on HDRA sensitivity were analyzed. HDRA was able to evaluate 379 of 424 assays (89.3%). In the CRT group, no significant correlation was confirmed between efficacy rate of 5-fluorouracil or cisplatin and histological findings in resected specimens after CRT. Efficacy rates of several anticancer agents using HDRA in the surgery group were observed in the range of 0.0-44.8%. On examination of clinical outcomes in the surgery group, in which patients with stage III received adjuvant chemotherapy, chemosensitivity-negative patients tended to display worse prognosis than chemosensitivity-positive patients. HDRA with MTT endpoint probably predicts the postoperative prognosis of patients with esophageal cancer.

Activation of phosphatidylinositol-3 kinase regulates pancreatic duodenal homeobox-1 in duct cells during pancreatic regeneration.

OBJECTIVE: The purpose of our study was to determine whether the phosphatidylinositol 3-kinase (PI3K)/Akt pathway contributes to expression of pancreatic duodenal homeobox-1 (PDX-1) in duct cells and the cell differentiation during pancreatic regeneration. METHODS: The role of PI3K in PDX-1 expression and duct cell differentiation with pancreatic regeneration in mice after partial pancreatectomy (Px) was examined using either wortmannin, a pharmacological PI3K inhibitor, or small-interfering RNA directed to the p85alpha regulatory subunit of PI3K. Akt phosphorylation, a marker of PI3K activation, and PDX-1 expression were assessed by Western blot analysis and immunohistochemistry. RESULTS: Both PDX-1 levels and Akt phosphorylation were concomitantly increased in pancreatic ducts after partial Px and, conversely, blocked by treatment with wortmannin or p85alpha small-interfering RNA. Pancreatic duct cell differentiation, as assessed by appearance of insulin-positive cells 3 days after partial Px, was effectively reduced by wortmannin. CONCLUSIONS: The PI3K/Akt activation plays a critical role for both PDX-1 expression and pancreatic duct cell differentiation into insulin-producing cells during pancreatic regeneration.

Evaluation of lymph node metastases in gastric cancer using magnetic resonance imaging with ultrasmall superparamagnetic iron oxide (USPIO): diagnostic performance in post-contrast images using new diagnostic criteria.

BACKGROUND: We assessed the value of magnetic resonance imaging (MRI), using ultrasmall superparamagnetic iron oxide (USPIO) with new diagnostic criteria, in the evaluation of regional lymph node metastases in gastric cancer. METHODS: Thirty-one patients with gastric cancer were enrolled. 1000 lymph nodes were dissected during surgery, and of these, 519 nodes (51.9%) were identified by currently used MRI imaging analysis. We evaluated lymph nodes on USPIO-post-contrast T2*-weighted images using the following two criteria: (1) we diagnosed the nodes on T2*-weighted images according to conventional criteria, where a node having an overall low signal intensity (pattern A) was nonmetastatic, while a node having partial (pattern B) or overall (pattern C) high signal intensity was metastatic; (2) we subdivided pattern B nodes on T1-weighted images using the new criteria, in which a node for which the high-intensity area on T2*-weighted images was not defined as adipose tissue on T1-weighted images (pattern B1) was metastatic, while a node for which the high-intensity area was defined as adipose tissue (pattern B2) was nonmetastatic. RESULTS: (1) The results using the conventional criteria were 96.2% sensitivity, 92.5% specificity, 76.3% positive predictive value (PPV), 99.0% negative predictive value (NPV), and 93.3% accuracy. (2) The results using the new criteria were 96.2% sensitivity, 98.3% specificity, 90.1% PPV, 99.0% NPV, and 97.1% accuracy. CONCLUSION: The assessment of lymph node metastases from USPIO-post-contrast MRI alone using the new criteria was useful in the diagnosis of regional lymph node metastases in gastric cancer.

CT and MR features of sclerosing mesenteritis mimicking a mesenteric metastasis from the carcinoid tumor.

Sclerosing mesenteritis is a rare and benign inflammatory entity characterized by fibrofatty thickening of the mesentery. To our knowledge, there are only a few reports on the features of sclerosing mesenteritis on magnetic resonance (MR) imaging and computed tomography (CT). In this present case, MR imaging demonstrated tissue characterization of fibrosis, and partial maximum intensity projection (MIP) and three-dimensional angiography images obtained using multislice CT clearly revealed the extent of the tumor and the vascular appearance affected by the mass. However, a mesenteric metastasis from the carcinoid tumor may show such imaging features. Therefore, when encountering such a case, we suggest that a tentative diagnosis of sclerosing mesenteritis be made, followed by a biopsy for intraoperative histopathologic analysis to avoid aggressive surgery.

Preoperative diagnosis of lymph node metastases in gastric cancer by magnetic resonance imaging with ferumoxtran-10.

BACKGROUND: Knowledge regarding the presence and location of lymph node metastasis in gastric cancer is essential in deciding on the operative approach. Lymph node metastases have been diagnosed with imaging tests such as computed tomography (CT) and ultrasonography (US); however, the accuracy of such diagnoses, based on size and shape criteria, has not been adequate. Ferumoxtran-10 (Combidex; Advanced Magnetics) is a lymphotropic contrast agent for magnetic resonance imaging (MRI) whose efficacy for the detection of metastatic lymph nodes in various cancers has been reported by several investigators; however, its efficacy for this purpose has not been reported for gastric cancer. We investigated the efficacy of ferumoxtran-10-enhanced MRI for the diagnosis of metastases to lymph nodes in gastric cancer. METHODS: Seventeen consecutive patients who were diagnosed with a nonearly stage of gastric cancer were enrolled in the study. All the patients were examined by MRI (Signa Horizon 1.5 T; GE Medical; T2*-weighted images) before and 24 h after the intravenous administration of ultrasmall particles of superparamagnetic iron oxide--ferumoxtran-10 (2.6 mg Fe/kg of body weight)--and the presence or absence of metastasis was determined from the enhancement patterns. The imaging results were compared with the corresponding histopathological findings following surgery. RESULTS: Of 781 lymph nodes dissected during surgery, the imaging results of 194 nodes could be correlated with their histopathological findings. Fifty-nine lymph nodes from 11 patients had histopathological metastases. In nonaffected normal lymph nodes, we observed dark signal intensity on MRI caused by the diffuse uptake of the contrast medium by macrophages resident in the lymph nodes, which phagocytose the iron oxide particles of ferumoxtran-10. The number of phagocytic macrophages was decreased in metastatic lymph nodes, and they showed various patterns of decreased uptake of ferumoxtran-10. Three enhancement patterns were observed in lymph nodes: (A) lymph nodes with overall dark signal intensity due to the diffuse uptake of ferumoxtran-10; (B) lymph nodes with partial high signal intensity due to partial uptake; and (C) no blackening of lymph nodes due to no uptake of ferumoxtran-10. Patterns (B) and (C) were defined as metastatic. The sensitivity, specificity, positive predictive value, negative predictive value, and overall predictive accuracy of postcontrast MRI were 100% (59/59), 92.6% (125/135), 85.5% (59/69), 100% (125/125), and 94.8% (184/194), respectively. These parameters for predictive accuracy were much superior to these parameters previously evaluated by CT or US. Nodes in the retroperitoneal and paraaortic regions were more readily identified and diagnosed on the MR images than those in the perigastric region. CONCLUSION: The present study confirmed that ferumoxtran-10-enhanced MRI is useful in the diagnosis of metastatic lymph nodes and that the use of this modality will be helpful in treatment decision-making for gastric cancer patients.

Detection of human epidermal growth factor receptor 2 protein and gene in fine needle aspiration cytology specimens and tissue sections from invasive breast cancer: can cytology specimens take the place of tissue sections?

Overexpression of HER2 protein and HER2 gene amplification in breast cancer are prognostic factors for the response to specific medical treatments such as trastuzumab, endocrine therapy, and chemotherapy. Whereas HER2 expression and gene amplification are generally examined in tissue sections, we investigated whether specimens from fine needle aspiration cytology (FNAC) are adequate for these analyses. HER2 protein overexpression and HER2 gene amplification were assessed in both FNAC specimens and tissue sections from 58 cases of invasive breast cancer. Immunohistochemistry assay for HER2 protein expression was performed according to the HercepTest protocol, and HER2 gene amplification was examined with the Spot-light CISH (chromogenic in situ hybridization) Detection kit. There was a significant positive correlation between assessments of HER2 protein status in the cytology specimens and tissue sections. The sensitivity, specificity, and accuracy of HER2 gene amplification detection in cytology specimens in relation to those in tissue sections were 84.0% (21/25 cases), 87.9% (29/33 cases), and 86.2% (50/58 cases), respectively. FNAC specimens are suitable for detection of HER2 overexpression and HER2 gene amplification in invasive breast cancer.

Preoperative esophageal cancer staging: magnetic resonance imaging of lymph node with ferumoxtran-10, an ultrasmall superparamagnetic iron oxide.

BACKGROUND: Accurate detection of metastasis to lymph nodes is an essential component of the approach to treatment. The purpose of this study was to evaluate the utility of magnetic resonance imaging with ferumoxtran-10 in diagnosing lymph node metastasis in esophageal cancer. STUDY DESIGN: Sixteen patients with esophageal cancer who were scheduled for surgical lymph node dissection were enrolled. All patients underwent MRI scanning before and 24 hours after intravenous administration of ferumoxtran-10, an ultrasmall, superparamagnetic iron oxide. The presence or absence of metastasis was identified in lymph nodes by their enhancement patterns. Nonmalignant nodes contained macrophages that phagocytosed ferumoxtran-10. Metastatic nodes exhibited a decrease in phagocytic activity, and consequently showed little or no uptake of ferumoxtran-10. So we subdivided the enhancement patterns into the following three patterns: (A) node having an overall low signal intensity, (B) node having an area of high signal intensity, and (C) node having an overall high signal intensity. We identified that patterns (B) and (C) were metastatic patterns. The imaging results were compared with histopathologic findings. RESULTS: Of the 408 resected lymph nodes, imaging results of 133 nodes could be compared with histopathologic findings. Twenty-four lymph nodes had histopathologic metastases. Using our enhancement criteria, sensitivity was 100%, specificity was 95.4%, and accuracy was 96.2% for diagnosis of metastatic nodes. CONCLUSIONS: Ferumoxtran-10 is useful for characterizing benign or malignant lymph nodes in esophageal cancer patients based on the defined enhancement criteria.