Cribriform-morular variant of Papillary Thyroid Carcinoma: Clue to Early Detection of Familial Adenomatous Polyposis-associated Colon Cancer

The cribriform-morular variant (CMV) of papillary thyroid carcinoma (PTC) is a rare histologic subtype of PTC that shows a combination of growth patterns including cribriform and spindle cell areas. The thyroid cancer with this unique histology was originally reported in patients with familial adenomatous polyposis (FAP), although it was later found in patients without polyposis as well. Because of its rarity, its clinical features are not clear. We reviewed seven patients with CMV-PTC who were found among 4194 patients with PTC in our pathology files between June 1991 and March 2003. The prevalence of CMV was 0.16% among all PTCs. We invited these patients to our hospital so we could obtain a detailed family history and recommend colonoscopic examination and germline APC gene analysis. Two patients without subjective symptoms had polyposis of the colon and colon cancers. Germline APC gene mutations were found in both patients. The father of a patient who refused the invitation was revealed to have undergone surgery for colon polyposis. In the remaining four patients, neither polyposis nor APC gene mutation was found. Common clinical features included a young age (mean 25 years), predominance of females, circumscribed tumors, negative node metastasis, and no recurrence of the thyroid cancer after surgery. Two of the three patients with colon polyposis had bilateral multiple thyroid tumors, whereas the remaining four (without polyposis) had a solitary tumor. The histopathology of CMV in patients with PTC should arouse a suspicion of FAP, especially if there are multiple tumors. This finding can lead to early detection of colon cancer.     

Rice-Based Diet and Cardiovascular Disease Mortality in Japan: From the Takayama Study

Rice is the staple food in Japan and many other Asian countries, but research on rice-based diets and cardiovascular disease is limited. We aimed to evaluate the association between rice consumption as grain dishes and cardiovascular disease mortality in comparison with bread and noodle consumption. The subjects were 13,355 men and 15,724 women aged ≥35 years who enrolled in the Takayama Study. Diet intake was assessed using a validated food-frequency questionnaire. Causes of death were identified from death certificates. Cardiovascular disease was defined according to the International Classification of Diseases and Health Related Problems, 10th Revision (code I00–I99). Hazard ratios in the second, third, and highest quartiles versus the lowest quartile of rice intake for cardiovascular disease mortality were 0.98, 0.80, and 0.78 for men, respectively (trend p = 0.013), but no significant association was observed among women. Rice intake was positively correlated with the intake of soy products and seaweed, and negatively correlated with the intake of meat and eggs. Neither bread nor noodles were associated with cardiovascular disease mortality. In Japan, choosing rice as a grain dish is likely to be accompanied by healthier foods as side dishes, which may have a potential role in the prevention of cardiovascular disease.     

Maspin expression is directly associated with biological aggressiveness of thyroid carcinoma.

Maspin belongs to the serpin superfamily and has been identified as a tumor suppressor because it inhibits cell motility, invasion, and angiogenesis. However, its physiological activity in carcinoma tissues seems to differ according to the origin of the carcinoma. In this study, we investigated maspin expression in thyroid neoplasms originating in follicular cells by means of immunohistochemistry. Neither normal follicular cells nor stromal cells expressed maspin. Follicular adenomas were all negative for maspin, but 12.5% of follicular carcinomas and 30.5% of papillary carcinomas were positive for it. However, the staining pattern was only focal in all positive specimens except for one and maspin-expressing cells were present mainly at the edge of carcinoma nests. Widely invasive follicular carcinomas tended to be more frequently positive for maspin than minimally invasive ones. In papillary carcinoma, maspin expression was directly linked to stage, tumor size, and extrathyroidal invasion. Papillary and follicular carcinomas involving lesions with solid, trabecular, or scirrhous growth patterns (poorly differentiated carcinoma as designated by Sakamoto et al.) expressed maspin in significantly higher incidence than those with pure papillary or follicular patterns. Furthermore, 48.2% of anaplastic (undifferentiated) carcinomas diffusely expressed maspin, and the rest were completely negative. These findings indicate that, in contrast to other carcinomas, maspin expression is directly associated with the biological aggressiveness of thyroid carcinoma. Further studies regarding the function of maspin in this carcinoma are required.     

Rationality/anti-emotionality personality and dietary habits in a community population in Japan

Background

There are no strong and consistent predictors of dietary habits although some associations have been shown with psychological factors. The purpose of the present study was to examine the relationships between the rationality and anti-emotionality (R/A) personality and dietary consumption in a Japanese community.

Methods

The Takayama study is a community-based cohort study on diet and cancer in Gifu, Japan, and was initiated on September 1, 1992. Cross-sectional analyses were conducted on dietary and lifestyle data. The consumption of 169 food and beverage items was measured along with portion size by using a food frequency questionnaire. Questions regarding the R/A-personality scale and lifestyle habits were included in the questionnaire. The participants were 28077 adults (13082 males and 14995 females) aged 35 years and over.

Results

Both males and females with high R/A-personality scores (i.e., high degree of rational thought and emotional repression) consumed more soy products, green and yellow vegetables, other vegetables, and seaweed than the other participants. Males with high R/A-personality scores drank fewer alcoholic beverages, and females with high scores were found to snack less on sweet and salty foods than the other participants. Males with high R/A-personality scores showed higher consumption of meat and dairy products, and females with high scores showed higher consumption of fish, shellfish, and eggs than those with low R/A-personality scores.

Conclusion

The R/A-personality scale may differentiate dietary habits in males and females in a Japanese community.Key words: Personality, Rationality, Repressed Emotion, Dietary Habits, Lifestyle     

Widening a narrow posterior mandibular alveolus following extirpation of a large cyst: a case treated with a titanium mesh-plate type distractor

Vertical alveolar augmentation by distraction osteogenesis has become a standard pretreatment of dental implants due to the main benefit of lack of donor site complications, and many reports have shown its benefit with various types of alveolar distractors. However, autogenous bone transplantation and/or guided bone regeneration techniques are still the standard treatment for correcting a narrow alveolar ridge because of few commercially available distractors for alveolar widening. In this article, we treated a case by a mesh-plate type of alveolar widening distractor for a narrow posterior mandibular alveolar ridge after extirpation of a large jaw cyst.     

Cetuximab-induced hypomagnesaemia aggravates peripheral sensory neurotoxicity caused by oxaliplatin

Calcium and magnesium replacement is effective in reducing oxaliplatin-induced neurotoxicity. However, cetuximab treatment has been associated with severe hypomagnesaemia. Therefore, we retrospectively investigated whether cetuximab-induced hypomagnesaemia exacerbated oxaliplatin-induced neurotoxicity. Six patients with metastatic colorectal cancer who were previously treated with oxaliplatin-fluorouracil combination therapy were administered cetuximab in combination with irinotecan alone or irinotecan and fluorouracil as a second-line treatment. All patients had normal magnesium levels before receiving cetuximab. The Common Terminology Criteria for Adverse Events version 3.0 was used to evaluate the grade of neurotoxicity, hypomagnesaemia, hypocalcaemia, and hypokalemia every week. All six patients had grade 1 or higher hypomagnesaemia after starting cetuximab therapy. The serum calcium and potassium levels were within the normal range at the onset of hypomagnesaemia. Oxaliplatin-induced neurotoxicity occurred in all patients at the beginning of cetuximab therapy, with grade 1 neurotoxicity in five patients and grade 2 in one patient. After cetuximab administration, the neurotoxicity worsened in all six patients, and three progressed to grade 3. Among the three patients with grade 3 neurotoxicity, two required a dose reduction and one had to discontinue cetuximab therapy. A discontinuation or dose reduction in cetuximab therapy was associated with exacerbated oxaliplatin-induced neurotoxicity due to cetuximab-induced hypomagnesaemia in half of patients who had previously received oxaliplatin. Therefore, when administering cetuximab after oxaliplatin therapy, we suggest serially evaluating serum magnesium levels and neurotoxicity.     

Specific binding of the WASP N-terminal domain to Btk is critical for TLR2 signaling in macrophages

Wiskott–Aldrich syndrome protein (WASP) is an adaptor molecule in immune cells. Recently, we revealed that WASP is involved in lipopolysaccharide-TLR4 signaling in macrophages by association of Bruton's tyrosine kinase (Btk) with the WASP N-terminal domain. Btk has been shown to play important roles in the signaling of several TLRs and to modulate the inflammatory response in macrophages. In this study, we evaluated the importance of the interaction between Btk and WASP in TLR2 signaling by using bone marrow-derived macrophage cell lines from transgenic (Tg) mice expressing anti-WASP N-terminal domain single-chain variable fragment (scFv) or V_L single-domain intrabodies. In this Tg bone marrow-derived macrophages, specific interaction between WASP and Btk were strongly inhibited by masking of the binding site in the WASP N-terminal domain. There was impairment of gene expression of TNF-α, IL-6, and IL-1β and phosphorylation of inhibitor of κB α/β (IKKα/β) and nuclear factor (NF)-κB upon stimulation with TLR2 ligands. Furthermore, tyrosine phosphorylation of WASP following TLR2-ligand stimulation was severely inhibited in the Tg bone marrow-derived macrophages, as shown by the impairment in WASP tyrosine phosphorylation following lipopolysaccharide stimulation. These results strongly suggest that the association between the WASP N-terminal domain and Btk plays an important role in the TLR2-signaling pathway in macrophages.