Epidemiological study of gastroenteropancreatic neuroendocrine tumors in Japan

Background

There have been few epidemiological studies on gastroenteropancreatic neuroendocrine tumors (GEP-NETs) in Japan.

Methods

We examined the epidemiology of GEP-NETs [pancreatic endocrine tumors (PETs) and gastrointestinal neuroendocrine tumors (GI-NETs)] in Japan in 2005 using a nationwide stratified random sampling method.

Results

A total of 2,845 individuals received treatment for PETs. Prevalence was estimated as 2.23/100,000 with an annual onset incidence of 1.01/100,000. Non-functioning tumor (NF)-PET constituted 47.4%, followed by insulinoma (38.2%) and gastrinoma (7.9%). Distant metastases were reported in 21% patients with NF-PETs and occurred more frequently as tumor size increased (>2 cm). Multiple endocrine neoplasia type 1 (MEN-1) was detected in 10% of PETs but only in 6.1% of NF-PETs. NF-PETs were detected incidentally by physical examination in 24% patients. In 2005, an estimated 4,406 patients received treatment for GI-NETs. Prevalence was estimated as 3.45/100,000, with an annual onset incidence of 2.10/100,000. The locations of GI-NETs varied: foregut, 30.4%; midgut, 9.6%; and hindgut, 60.0%. Distant metastases were observed in 6%. Lymph node metastases occurred more frequently as tumor size increased (>1 cm). The frequency of MEN-1 complications was 1%. Physical examination revealed GI-NETs in 44% patients. The frequency of symptomatic GI-NETs was 3.4%. Interestingly, 77.1% of patients with foregut GI-NETs had type A gastritis.

Conclusion

Our results show there are large differences in GEP-NETs between Japan and Western nations, primarily due to differences in the presence of MEN-1 in NF-PETs and the location, symptomatic status, and prevalence of malignancy in GI-NETs.     

Bezafibrate for the treatment of primary sclerosing cholangitis

Background

It is known that bezafibrate decreases serum alkaline phosphatase (ALP) in patients with hyperlipidemia, and the efficacy of this drug for the treatment of primary biliary cirrhosis has been confirmed. However, there has been little evidence of its efficacy for the treatment of primary sclerosing cholangitis (PSC).

Methods

Bezafibrate (400 mg/day) was orally administered to 7 consecutive patients with PSC, and we analyzed their clinical features and the drug efficacy in terms of the effect on hepatobiliary enzymes, including ALP, gamma-glutamyl transpeptidase (γ-GTP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) after 6 months. The latest hepatobiliary enzyme levels were also evaluated.

Results

In 3 patients (effective group), the levels of all hepatobiliary enzymes had decreased after 6 months. Mean ALP had decreased to approximately 40% of the baseline in this group. The efficacy of bezafibrate was observed for a long period (range, 8–27 months) in these 3 patients. There seemed to be no definite association between the efficacy of bezafibrate and the clinical features in the short term.

Conclusions

This study showed that bezafibrate could lower the levels of hepatobiliary enzymes in about half of a cohort of patients with PSC.     

Repair in osteonecrosis of the femoral head: MR imaging features at long-term follow-up

The purpose of this study was to evaluate retrospectively the progression of reparative changes in osteonecrosis of the femoral head over a long period of time, using both serial plain films and magnetic resonance (MR) images. The subjects were 25 patients with 33 hips affected by osteonecrosis, followed conservatively for more than 10 years (mean, 14.1; range, 10 to 23.4). At the latest follow-up examination, there were 11 hips at the non-collapse stage, 17 hips at the collapse stage where collapse has ceased, and five hips at the osteoarthritic stage. An increase in radiographic sclerosis of the lesion area was seen in 14 of 17 hips which showed cessation of collapse, 13 of which showed an intralesional area with intermediate signal intensity on fat suppression MR images. Four of five hips at the osteoarthritic stage also showed an intralesional area with intermediate signal intensity on fat suppression MR images. Ten of 11 hips at the non-collapse stage showed a normal fat signal intensity area demarcated with a low-signal-intensity band on T1-weighted MR images. In the 24 hips followed for more than 5 years with MR imaging (mean, 9.2; range, 5.9 to 13.8), changes of lesion size of abnormal signal intensity on T1-weighted MR images were not observed. In conclusion, reparative process was limited to the periphery of osteonecrosis over a long period of time unless collapse had occurred. If collapse had ceased minimally, the reconstructive repair process could be facilitated.     

Histological evaluation of intracapsular venous invasion for discrimination between portal and hepatic venous invasion in hepatocellular carcinoma

Background and Aim:  Histological criteria for intracapsular venous invasion (IVI) that would allow its discrimination between portal and hepatic venous invasion in hepatocellular carcinoma (HCC) have not been established.
Methods:  We evaluated IVI immunohistochemically to discriminate between portal and hepatic venous invasion in 89 resected specimens from patients with HCC. IVI was defined as the microscopic involvement of the vessels within the fibrous capsule of HCC. The hepatic venous system was subdivided into the central vein and the sublobular/hepatic vein. Immunohistochemical analysis with the D2-40 monoclonal antibody revealed lymphatic vessels.
Results:  In non-neoplastic liver tissues, the portal veins ( n  = 4355) were accompanied by lymphatic vessels (99.7%), bile ductules (100%) and arteries (96%), whereas the central veins ( n  = 3932) and sublobular/hepatic veins ( n  = 662) were rarely accompanied by lymphatic vessels (0% and 17%, respectively) and bile ductules (12% and 33%, respectively). In total, 29 IVI foci were detected; three foci were clearly visible within vessels that contained a distinct layer of connective tissue fibers, signifying sublobular/hepatic venous invasion. As the remaining 26 foci were accompanied by lymphatic vessels (26/26 [100%]), bile ductules (21/26 [81%]) and arteries (10/26 [38%]), these foci were considered to reflect intracapsular portal venous invasion rather than venous invasion of the central vein. Intracapsular portal venous invasion was significantly associated with extratumoral portal venous invasion ( P  < 0.001).
Conclusions:  D2-40 immunoreactivity for the histological evaluation of IVI in HCC allows discrimination between portal and hepatic venous invasion for cases in which portal venous invasion predominates.     

Surgical resection of gastrointestinal stromal tumor of esophagus following preoperative imatinib treatment: a case report

We report a case of esophagectomy after a primary esophageal gastrointestinal stromal tumor (GIST) was preoperatively treated with imatinib mesylate. A 71-year-old woman was diagnosed with an esophageal submucosal tumor by upper gastrointestinal endoscopy at her health checkup. The tumor was located at the lower thoracic esophagus immediately above the esophagogastric junction and measured 4.5 cm in size. It was diagnosed as GIST of the esophagus for reasons of its high susceptibility to imatinib mesylate. Preoperative treatment with imatinib was performed in an attempt to preserve the esophagus. Although the tumor size was decreased by 36% after the 6-month treatment, transhiatal esophagectomy was required for complete resection, and esophageal preservation could not be accomplished.     

A case of metastatic esophageal tumor from breast cancer

A 58-year-old woman was admitted to our hospital with the complaint of dysphagia that had developed 37 months after initiation of treatment for breast cancer. Endoscopy revealed severe stenosis 32 cm from the incisors through which the endoscope could not pass. No mucosal irregularities were observed, and biopsies of the stenotic lesion were negative for malignancy. Computed tomography showed wall thickening of the midthoracic esophagus and left pleural effusion, which had increased metabolic activity as detected by ¹⁸F-fluorodeoxyglucose positron emission tomography. Cytological examination of the pleural effusion showed adenocarcinoma compatible with metastasis from a prior lobular carcinoma of the breast. Vinorelbine effectively relieved her symptoms, and the disease stabilized for approximately 1 year. However, she died 16 months after the diagnosis of metastatic esophageal tumor from the preceding breast cancer.     

Lack of skin carcinogenicity of topically applied titanium dioxide nanoparticles in the mouse

This study was conducted to examine the post-initiation carcinogenic potential of coated and uncoated titanium dioxide nanoparticles (CTDN and UCTDN) using a mouse medium-term skin carcinogenesis bioassay. For this purpose, 5, 10 and 20 mg/animal doses of CTDN or UCTDN were applied to mouse skin in the post-initiation phase (up to 20 weeks) in a two-stage skin carcinogenesis model using 7 week old CD1 (ICR) female mice. 7,12-dimethylbenz[a]anthracene (DMBA) and 12-o-tetradecanoylphorbol 13-acetate (TPA) were used as the initiator and a positive control promoter, respectively. Pentalan 408 served as a vehicle control. No changes in survival rate, general condition and body weight related to the test materials were observed. On macroscopic observation, 1-2 nodules/group on the skin were observed in each group applied CTDN and UCTDN as well as the control group after DMBA initiation. The nodules were histopathologically diagnosed as squamous cell hyperplasia, sebaceous gland hyperplasia, squamous cell papilloma and keratoacanthoma. CTDN and UCTDN experiments, while enlargement of the mandibular, pancreatic, lumbar region and inguinofemoral lymph nodes, spleen and thymus was observed in mice given 5 and 10 mg but not 20 mg, the lack of dose-dependence suggests no biological significance.In the present study, CTDN and UCTDN applied in post-initiation stages at doses of up to 20 mg/mouse did not increase the development of nodules, and thus it was concluded that titanium dioxide nanoparticles do not possess post-initiation potential for mouse skin carcinogenesis.