There were 83 cases of usual interstitial pneumonia (UIP) in 3712 consecutive autopsy cases during 1972 to 1992 in Toranomon Hospital. Primary lung cancer had arisen in 40 cases of UIP in that period. The prevalence of lung cancer (48.2%) in UIP was significantly higher than that of lung cancers (9.1%) in the age‐matched general population without UIP (P < 0.001). The prevalence of association of multiple lung cancer in UIP (20.W0) was also significantly increased. Thus, UIP showed a remarkable potency to develop lung cancers. The lung cancer cases in UIP had obvious smoking habits. Both the rates of smokers and the quantity of smoking were significantly increased in the lung cancer cases in UIP (P < 0.05). There was a distinct anatomical distribution of lung cancer in UIP. Most cancers in UIP (98%) arose in the peripheral area of the lung (P < 0.001, compared to lung cancer cases without UIP) with close relation to the honeycombing lesion. Studies on surgical specimens with small cancers showed that most tumors in UIP arose in the border area between honeycombing and the non‐fibrotic area. Thus, the front of the remodeling of the lung is suspected to be a potential field of developing lung cancer. The chronic inflammatory process resulting in the remodeling of the lung may play an important part in the development of lung cancer in UIP under the circumstance of heavy smoking.

Somatostatinomas are rare functioning neoplasms usually arising in the pancreas and duodenum. We report a case of somatostatinoma in a 42-year-old male with neither neurofibromatosis nor somatostatinoma syndrome. A large tumor in the descending duodenum had given rise to multiple lymph node metastases. An additional 31 duodenal somatostatinoma cases were also reviewed. Most originated in the descending part of the duodenum, with the ampulla and peri-ampullary area as the most common sites (60%). Frequent manifestations were abdominal pain (25%), jaundice (25%), or cholelithiasis (19%), the latter two reflecting obstruction of the bile duct by tumors. Only two cases showed a possible somatostatinoma syndrome (6%). The tumors with metastases, lymph nodes (10) and liver (2), were significantly larger than average than those without (2.91 +/- 1.49 cm vs 1.36 +/- 0.71 cm, P < 0.05). With a cut-off point of 2.0 cm, diagnostic accuracy for metastasis was 77.78% with 87.50% specificity and 63.64% sensitivity. The smallest tumor with metastases was 0.8 cm and the largest without metastases was 3.0 cm. These results indicate that duodenal somatostatinomas are malignant by nature and the risk of metastasis significantly increases with tumors larger than 2.0 cm.

Vascular calcification, especially medial artery calcification, is associated with cardiovascular death in patients with diabetes mellitus and chronic kidney disease (CKD). To determine the underlying mechanism of vascular calcification, we have demonstrated in our previous report that advanced glycation end-products (AGEs) stimulated calcium deposition in vascular smooth muscle cells (VSMCs) through excessive oxidative stress and phenotypic transition into osteoblastic cells. Since AGEs can induce apoptosis, in this study we investigated its role on VSMC apoptosis, focusing mainly on the underlying mechanisms. A rat VSMC line (A7r5) was cultured, and treated with glycolaldehyde-derived AGE-bovine serum albumin (AGE3-BSA). Apoptotic cells were identified by Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. To quantify apoptosis, an enzyme-linked immunosorbent assay (ELISA) for histone-complexed DNA fragments was employed. Real-time PCR was performed to determine the mRNA levels. Treatment of A7r5 cells with AGE3-BSA from 100 µg/mL concentration markedly increased apoptosis, which was suppressed by Nox inhibitors. AGE3-BSA significantly increased the mRNA expression of NAD(P)H oxidase components including Nox4 and p22phox, and these findings were confirmed by protein levels using immunofluorescence. Dihydroethidisum assay showed that compared with cBSA, AGE3-BSA increased reactive oxygen species level in A7r5 cells. Furthermore, AGE3-induced apoptosis was significantly inhibited by siRNA-mediated knockdown of Nox4 or p22phox. Double knockdown of Nox4 and p22phox showed a similar inhibitory effect on apoptosis as single gene silencing. Thus, our results demonstrated that NAD(P)H oxidase-derived oxidative stress are involved in AGEs-induced apoptosis of VSMCs. These findings might be important to understand the pathogenesis of vascular calcification in diabetes and CKD.

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