Clinicopathological features,diagnosis, and treatment of sessile serrated adenoma/polyp with dysplasia/carcinoma

Sessile serrated adenoma/polyps (SSA/Ps) are early precursor lesions in the serrated neoplasia pathway, which results in BRAF‐mutated colorectal carcinomas with not only high levels of microsatellite instability but also microsatellite stable. SSA/Ps with advanced histology, including cytological dysplasia or minimally invasive carcinomas, are important lesions because SSA/Ps are considered major contributors to “interval cancers” and these lesions can rapidly become dysplastic or invasive carcinomas. Clinicopathologically, SSA/Ps with dysplasia or invasive carcinoma were associated with advanced age, female sex, and proximal colon. Although SSA/Ps with submucosal invasive carcinoma were smaller and invaded less deeply into the submucosal layer than conventional tubular adenomas with submucosal invasive carcinoma, SSA/Ps with submucosal invasive carcinoma frequently had a mucinous component and exhibited a higher potential for lymphatic invasion and lymph node metastasis. In an SSA/P series, endoscopic characteristics, including (semi)pedunculated morphology, double elevation, central depression, and reddishness, may help accurately diagnose SSA/Ps with advanced histology. Removal of SSA/Ps with dysplasia or invasive carcinoma was recommended. Endoscopic treatment such as endoscopic mucosal resection or endoscopic submucosal dissection is useful for those lesions. However, surgical resection with lymph node dissection might be indicated when SSA/Ps with invasive carcinoma are endoscopically suspected, because these have the high risk of lymph node metastasis. Greater awareness may promote further research into improving the detection, recognition, and complete resection rates of SSA/Ps with dysplasia or invasive carcinoma and reduce the interval cancer rates.     

Genetic variations of HSD11B2 in hypertensive patients and in the general population, six rare missense/frameshift mutations.

Mutations in the gene encoding 11beta-hydroxysteroid dehydrogenase type 2, HSD11B2, cause a rare monogenic juvenile hypertensive syndrome called apparent mineralocorticoid excess (AME). In AME, defective HSD11B2 enzyme activity results in overstimulation of the mineralocorticoid receptor (MR) by cortisol, causing sodium retention, hypokalemia, and salt-dependent hypertension. Here, we have studied whether genetic variations in HDS11B2 are implicated in essential hypertension in Japanese hypertensives and the general population. By sequencing the entire coding region and the promoter region of HDS11B2 in 953 Japanese hypertensives, we identified five missense mutations in 11 patients (L14F, n = 5; R74H, n = 1; R147H, n = 3; T156I, n = 1; R335H, n = 1) and one novel frameshift mutation (4884Gdel, n = 1) in a heterozygous state, in addition to 19 genetic variations. All genetic variations identified were rare, with minor allele frequencies less than 0.005. Four of 12 patients with the missense/frameshift mutations showed renal failure. Four missense mutations, L14F, R74H, R147H, and R335H, were successfully genotyped in the general population, with a sample size of 3,655 individuals (2,175 normotensives and 1,480 hypertensives). Mutations L14F, R74H, R147H, and R335H were identified in hypertensives (n = 6, 8, 3, and 0, respectively) and normotensives (n = 8, 12, 5, and 0, respectively) with a similar frequency, suggesting that these missense mutations may not strongly affect the etiology of essential hypertension. Since the allele frequency of all of the genetic variations identified in this study was rare, an association study was not conducted. Taken together, our results indicate that missense mutations in HSD11B2 do not substantially contribute to essential hypertension in Japanese.     

A sewing needle completely buried in the myocardium removed under extracorporeal circulation.

A 14-year-old boy had a needle accidentally inserted through his chest wall. Chest X-ray showed a needle-shaped metallic density localized in the cardiac silhouette. An echocardiography indicated the needle had passed through the interventricular septum, and its eye and point had reached the right and left ventricle, respectively. Surgical removal of the needle was performed. The needle could not be observed from the heart surface, and was recognized in a dent 5 mm on the right side from the left anterior descending branch (LAD). The needle was easily removed under extracorporeal circulation, and he was discharged ten days after the operation.     

Fit and fill analysis of a newly designed femoral stem in cementless total hip arthroplasty for patients with secondary osteoarthritis

The fit and fill of the femoral canal are critical to the success of cementless femoral stems in total hip arthroplasty. It is difficult for conventional stems to provide a good fit and fill for the femora of patients with secondary osteoarthritis. Based on measurements of 100 femora of these patients, we designed two types of Fukui Medical School (FMS) stems with a proximal lateral flare that differed in the medial radius. We compared the fit and fill of the FMS stems with those of four conventional stems, using computer simulation. The mean proximal fit and total fit of the FMS stems were 46% and 53% respectively, a significant improvement compared with the other stems examined. The mean fill of FMS stems was 82% at the lower end of the lesser trochanter and 84% at the upper end of the isthmus, values that were significantly higher than those of the other stems. Since September 1995, we have implanted FMS stems in 15 hips with secondary osteoarthritis. Radiographic evaluations showed that the canal fill of the FMS stems was significantly greater in the proximal femur compared with other stems previously inserted at our department. A summary of this paper was presented at the 9th Symposium on Computer-Assisted Radiology; June 1995, Berlin, and at the 8th International Symposium on Technology in Arthroplasty; September 1995, Puerto Rico.     

Osteoclastogenesis inhibitory factor exhibits hypocalcemic effects in normal mice and in hypercalcemic nude mice carrying tumors associated with humoral hypercalcemia of malignancy

Osteoclastogenesis inhibitory factor (OCIF) is a novel secreted protein that inhibits osteoclastogenesis both in vitro and in vivo. In this study, we examined the effects of OCIF on serum calcium (Ca) concentrations in normal mice and in hypercalcemic nude mice carrying tumors associated with humoral hypercalcemia of malignancy. In normal mice, a single intraperitoneal injection of OCIF reduced serum Ca levels in a dose-dependent manner. Significant decrease in serum Ca (by 1.6 ± 0.3 mg/dL, n = 5) was observed 2 h after the injection of OCIF at 20 mg/kg and the hypocalcemic effect continued for up to 12 h. Serum phosphate (Pi) concentrations also decreased in response to OCIF. Urinary excretion of Ca, Pi, and creatinine did not change significantly after injection of OCIF or vehicle. In hypercalcemic, tumor-bearing nude mice, a single intraperitoneal injection of OCIF at 20 mg/kg resulted in a dramatic decrease in serum Ca (maximal decrease 2.8 ± 0.37 mg/dL, n = 11), which continued for up to 24 h. The results suggest that OCIF decreased serum Ca through its inhibitory effect on bone resorption. Furthermore, it is suggested that OCIF has therapeutic potential for the treatment of hypercalcemic conditions such as malignancy-associated hypercalcemia.     

Pharmacological studies of 6-amidino-2-naphthyl 4-[(4,5-dihydro-1H-imidazol-2-yl)amino]benzoate dimethanesulfonate. Effects on experimental pancreatitis

The effects of FUT-187 (6-amidino-2-naphthyl 4-[(4,5-dihydro-1H-imidazol-2-yl)amino]benzoate dimethanesulfonate, CAS 103926-82-5), a novel synthetic protease inhibitor, were examined in experimental rat and canine models of pancreatitis. 1. FUT-187 significantly increased the survival of rats with trypsin- and phospholipase A2-induced pancreatitis in a dose-dependent manner (10-100 mg/kg, p.o.). 2. FUT-187 decreased plasma enzymatic activity reflecting the degree of pancreatitis in rats with ethionine-induced pancreatitis, and showed a tendency to ameliorate histopathological changes in the pancreas (10-100 mg/kg p.o.). 3. FUT-187 (10 mg/kg) produced an obvious improvement of various biochemical parameters of pancreatitis and also reduced histopathological changes in the pancreas in animals with experimental pancreatitis produced by the closed duodenal loop method. In addition, FUT-187 significantly increased the survival of dogs when given by direct administration into the lumen of the closed duodenal loop. The therapeutic effects of FUT-187 in experimental pancreatitis were nearly equal in most instances to those of camostat mesilate. Thus, FUT-187 would appear to be an effective new agent for the treatment of pancreatitis.     

Living domino liver transplantation in an adult with congenital absence of portal vein.

Congenital absence of the portal vein (CAPV) is a rare malformation of the splanchnic venous system. Although CAPV is usually detected in the pediatric age group, our patient was a 35-year-old woman. She had been diagnosed with CAPV in 1996 when she was 27 years old. In 1998, she was placed on hemodialysis due to chronic renal failure. After several episodes of encephalopathy in 2002, liver transplantation (LT) was recommended to her and her family. Since there was no suitable living donor candidate, she was put on the waiting list for a deceased donor liver transplant in Japan. In 2004, her ammonia level increased to around 300 microg/dl, and she went into a coma lasting for three days. After recovering from this event, she underwent a living domino transplantation using a whole liver donated by a familial amyloid polyneuropathy (FAP) patient. Her portal vein, which had drained directly into the inferior vena cava (IVC), was transected together with a cuff of the IVC wall and anastomosed to the graft liver portal vein in an end-to-end fashion. In conclusion, liver transplantation proved to be a safe and effective way to save this patient and improve her quality of life.