A novel anti-MUC1 antibody against the MUC1 cytoplasmic tail domain: use in sensitive identification of poorly differentiated cells in adenocarcinoma of the stomach

Background

Isolated cancer cells of non-solid type poorly differentiated adenocarcinoma (por2) or signet-ring cell carcinoma (sig) are frequently seen in scirrhous gastric cancers with a very poor prognosis. These cells are often scattered in granulation tissue or desmoplastic fibrotic tissue and tend to be overlooked in routine pathological examination. We aimed to raise a novel antibody that can identify the isolated cancer cells easily.

Methods

Because the MUC1 cytoplasmic tail domain (CTD) has many biological roles including tumor progression and cell adhesion disturbance and is expected to be expressed in isolated cancer cells, we raised a novel monoclonal antibody (MAb) MUC1-014E against an intracellular nonrepeating 19-amino-acid sequence (RYVPPSSTDRSPYEKVSAG: N-1217-1235-C) of the MUC1 CTD, using a synthetic peptide including the 7-amino-acid epitope (STDRSPY: N-1223-1229-C).

Results

In the immunohistochemical staining of 107 gastrectomy specimens including 48 por2 and 31 sig lesions, the MAb MUC1-014E showed high rates of positive staining (≥5% of carcinoma cells stained) for por2 (100%) and sig (97%), and of the highest intensity staining (4+, ≥75% of carcinoma cells stained) for por2 (100%) and sig (90%). In the 89 biopsy specimens including 82 por2 and 38 sig lesions, the MAb MUC1-014E showed high rates of positive staining for por2 (100%) and sig (100%) and of 4+ staining for por2 (87%) and sig (84%). All the rates were significantly higher than those with cytokeratins (AE1/AE3 or CAM5.2).

Conclusions

The MAb MUC1-014E is very useful for accurate detection of isolated cancer cells in scirrhous gastric cancers.     

Coexistence of pyriform sinus fistula, ectopic lingual thyroid, and ectopic cervical thymus

Objective

We report an extremely rare case of coexistence of pyriform sinus fistula, ectopic lingual thyroid, and ectopic cervical thymus.

Case report

A 16-year-old girl with ectopic lingual thyroid had suffered repetitive painful swelling in the left anterior neck. Barium swallow radiography and computed tomography revealed a fistula arising from the pyriform sinus running down to the anterior neck. She underwent transcervical fistulectomy with preservation of the recurrent laryngeal nerve. Histopathological examination of the surgical specimen showed coexisting thymic tissue.

Conclusion

This illustrative case exemplifies the different embryological origin of the thyroid from that of the third and fourth pharyngeal pouch derivatives.     

Favorable response of heavily treated wilms' tumor to Paclitaxel and Carboplatin

Background: Heavily treated Wilms' tumor responding to the combination of paclitaxel and carboplatin has not yet been reported. Case Report: A 17-year-old man presented with hematuria. He received a diagnosis of Wilms' tumor with multiple lung metastases and was treated with preoperative chemotherapy including vincristine, dactinomycin, and doxorubicin, a right nephrectomy, and adjuvant chemotherapy, followed by pulmonary metastasectomy. During the next 8 years, he suffered from 4 relapses and has been treated with multiple anticancer agents including high-dose chemotherapy with autologous peripheral blood stem cell transplantation. Finally, the disease progressed due to peritoneal and pleural metastases. With opioid administration for left shoulder pain due to pleural metastasis, he received combination chemotherapy with carboplatin (area under the curve = 4) and paclitaxel (175 mg/m(2)) on day 1. After 2 cycles, he achieved a partial response with mild toxicity. He received 7 cycles of the chemotherapy and the time to progression was 200 days. Conclusion: In a refractory case after intensive treatments, we succeeded to control the disease for a while.     

Poor Glycemic Control is a Significant Predictor of Cardiovascular Events in Chronic Hemodialysis Patients With Diabetes

We investigated the impact of glycemic control on the emergence of cardiovascular disease (CVD) in diabetic patients who were on maintenance hemodialysis in a prospective observational study. One hundred and thirty‐four diabetic hemodialysis patients (63 ± 10 years‐old, hemodialysis duration of 4.5 ± 3.9 years) at a single dialysis center were enrolled. The cohort was observed prospectively for 5 years, and the emergence of fatal and non‐fatal CVD was recorded. Patients were categorized into two groups; good (mean hemoglobin (Hb) A1C <7.0%, N = 65) and poor HbA1C (mean HbA1C ≥7.0%, N = 69). The relationship between glycemic control and CVD emergence was evaluated by Kaplan‐Meier estimation and Cox proportional hazard models. During the follow‐up period, 50 CVD events were observed. The cumulative CVD incidence in the poor HbA1C group was significantly higher than that of the good HbA1C group, as determined by Kaplan‐Meier estimation (P = 0.0250, log‐rank test). After adjustment for gender, age, duration of dialysis, and past history of CVD, a multivariate Cox proportional hazard model showed that poor HbA1C was a significant predictor of CVD events (hazards ratio [HR] 1.828 [95% CI, 1.008–3.314], P = 0.0470). When ischemic heart disease, cerebral infarction, and arteriosclerosis obliterans were determined as an endpoint, both HbA1C levels and the poor HbA1C group were significant predictors for the emergence of CVD (HR 1.269 per 1% HbA1C [95%CI, 1.022–1.574], P = 0.0307,and HR 2.816 [95% CI, 1.377–5.759], P = 0.0046, respectively). In diabetic hemodialysis patients, poor glycemic control is a significant, independent predictor of the emergence of CVD, indicating the importance of careful management of glycemic control in hemodialysis patients.     

Dynamic monitoring of brain activation under visual stimulation using fMRI--the advantage of real-time fMRI with sliding window GLM analysis

An fMRI technique based on real-time analysis was applied to evaluate the advantages of dynamic monitoring of the t-statistics based on a general linear model. The temporal change of the t-statistics in V1 and V4 under four conditions of visual stimuli covering different visual fields with or without coloring was estimated using an incremental analysis and a sliding window analysis (SWA). The SWA not only visualized the dynamic change of the activation in response to the task conditions and switching, but also enabled us to evaluate the temporal correlation of the t-statistics among the four visual areas. It was suggested that the activity in the V4 was bilaterally organized, and the altering color stimuli gave stronger stimulation to the V1 than did the black and white stimuli. Although the activation map at each time point represents the brain activity during several task and rest blocks, a SWA will be useful to evaluate the transition of neuronal activation in response to several sequential task conditions. An incremental analysis will be useful to monitor the ongoing activation in real-time during the scan, since it gives a higher t-value according to the accumulation of volume data. These two methods will be complementary.