Association of gBRCA1/2 mutation locations with ovarian cancer risk in Japanese patients from the CHARLOTTE study

Whether germline (g) breast cancer susceptibility gene (BRCA) mutations are located within or outside the ovarian cancer cluster region (OCCR) (1380‐4062 bp for gBRCA1, and between 3249‐5681 bp and 6645‐7471 bp for gBRCA2) may influence risk variations for ovarian cancers. This ad hoc analysis of the CHARLOTTE epidemiological study in Japan assessed the distribution of gBRCA1/2 mutations in patients with newly diagnosed ovarian cancer, and investigated an association between gBRCA1/2 mutation locations and ovarian cancer risk. Differences in patient background and clinical characteristics in subgroups stratified by gBRCA1/2 mutation locations were also evaluated. We analyzed the data of 93 patients (14.7%) from the CHARLOTTE study who were positive for gBRCA1/2 mutations. After excluding 16 cases with L63X founder mutation, 28 (65.1%) of gBRCA1 mutations were within the OCCR. Of 30 gBRCA2 mutations, 15 (50.0%) were within the OCCR. Of 27 patients (one patient excluded for unknown family history) with gBRCA1 mutations located in the OCCR, 11 (40.7%) had a family history of ovarian cancer; the proportion of patients with a family history of ovarian cancer and gBRCA1 mutations outside the OCCR was lower (13.3%). Sixty percent of patients with gBRCA1 mutations outside the OCCR had a family history of breast cancer; the proportion of patients with a family history of breast cancer and gBRCA1 mutations within the OCCR was relatively lower (33.3%). Understanding the mutation locations may contribute to more accurate risk assessments of susceptible individuals and early detection of ovarian cancer among gBRCA mutation carriers.     

Two cases of mesenteric panniculitis]

Two patients with mesenteric panniculitis are presented. In the first patient, a provisional diagnosis of ileus was made, based on the clinical features and imaging data. Laparotomic findings showed that the ileum was bound tightly by a fibrous strip and dilated, with thickened and swollen mesentery. Incision of the fibrous strip was performed, and the clinical symptoms were improved. The second patient was strongly suspected to have mesenteric panniculitis, from characteristic features on abdominal computed tomography and barium enema. Conservative therapy was effective in this case. We emphasize the variety of clinical courses in mesenteric panniculitis, requiring selection of the most suitable treatment.     

Expression of vascular endothelial growth factor and angiogenesis in patellar tendon grafts in the early phase after anterior cruciate ligament reconstruction

The aim of this study was to clarify vascular endothelial growth factor (VEGF) expression and angiogenesis in the patellar tendon (PT) autograft in the early phase after anterior cruciate ligament (ACL) reconstruction using a rabbit model. The right knees of 30 Japanese white rabbits underwent ACL reconstruction using the medial third of the PT complex. We evaluated the grafted tendon at 1, 2, 3, 4, and 8 weeks after ACL reconstruction by immunohistology for proliferating cell nuclear antigen, VEGF, and CD31, which is a marker for vascular endothelial cells. At week 1 , few cells were observed at the midsubstance of the grafted tendon. A number of proliferating cells were observed at the surface area of the PT graft 2 weeks after graft transplantation, while no vessel formation was observed in the graft at the same time. VEGF was highly expressed 2-3 weeks postoperatively. Vessel formation in the PT graft increased with time from 3 to 8 weeks after ACL reconstruction. The rates of proliferating cells and VEGF-expressing cells decreased with time from 3 to 8 weeks. This study has suggested that VEGF is involved in the graft remodeling process particularly at the early phase after ACL reconstruction.     

Intrapulmonary metastasis developing eighteen years after complete resection of thymoma

We present a case of intrapulmonary metastasis developing 18 years after complete resection of thymoma. An 8 mm nodule in the lower lobe of the left lung was noted on chest X-ray in a 76-year-old woman who had undergone complete resection of Masaoka’s stage II thymoma 18 years earlier. Since the nodule grew to 17 mm during a 2-year follow-up, wedge resection was performed. The lesion was histologically diagnosed as an intrapulmonary metastasis from thymoma. Extremely late recurrence after complete resection of thymoma is discussed.     

Congenital quadricuspid aortic valve with tetralogy of Fallot and pulmonary atresia

We report the case of a 4-year-old girl who had quadricuspid aortic valve regurgitation with tetralogy of Fallot and pulmonary atresia. This combination is very uncommon. Aortic valve replacement was performed successfully due to aortic regurgitation which had progressed one year after the total repair. The dilated aortic annulus plus quadricuspid aortic valve may result in progressive aortic regurgitation for a short period.     

Effects of a new dihydropyridine calcium antagonist on vascular smooth muscles, cardiac muscles and [3H]-nitrendipine binding

The effects of methyl 2,6-dimethyl-4-(2-nitrophenyl)-5-(2-oxo-1,3,2-dioxaphosphorinan-2- yl)-1,4- dihydropyridine 3-carboxylate (DHP-218), a new dihydropyridine calcium antagonist, on vascular smooth muscles, cardiac muscles and [3H]-nitrendipine binding to the cardiac muscle and brain membranes were investigated in vitro. Vascular smooth muscles: Calcium-induced contraction of the rat aorta in high K+ solution was inhibited by DHP-218 with the pA2 value of 9.11. The IC50 value for the inhibitory effects of this compound in high K+-induced and phenylephrine-induced contraction was 6.3 nmol/l and 66 nmol/l, respectively. Vasodilatory effects of this drug on various blood vessels of rabbits contracted by high K+ appeared to a similar extent. The onset of the vasodilatory effect was very slow and the recovery rate of vasodilatory response after washout with the bathing solution containing high K+ or phenylephrine was also very slow. Cardiac muscles: Negative chronotropic and inotropic actions were observed at concentrations more than 30 and 100 nmol/l, respectively. Duration of the plateau phase of normal action potential was shortened and the amplitude and duration of slow action potential were reduced at concentrations more than 1 mumol/l. Very high vasculoselectivity was observed. Displacement of [3H]-nitrendipine binding: The pattern of displacement of [3H]-nitrendipine binding by DHP-218 was very similar to that of other 1,4-dihydropyridines but this compound was about 70 times less potent than nifedipine in [3H]-nitrendipine displacement capacity. These results indicate that DHP-218 has specific vasodilatory action due to calcium antagonism, but association and dissociation rates with tissue and receptors were different from those of nifedipine.     

Anti-tumor activity of human recombinant TNF against human malignant glioma cell lines and combined effect with Hu INF-beta

Human TNF was detected fairly recently and at present the anti-tumor activity of human recombinant TNF is being examined against various malignant tumors of human origin. In the present study, we report the anti-tumor activity of recombinant human TNF against human malignant glioma cell lines in vitro and in vivo, in addition to its combined effects with HuIFN-beta. The in vitro study was conducted as follows. Thirteen human glioma cell lines were exposed to 100 U/ml TNF, 1,000 IU/ml HuIFN-beta, or both, and the suppression rate was calculated on days 3, 5 and 7. In the in vivo study, nude mice carrying a human glioma cell line, KMS II, in the subcutaneous tissues were divided into groups and drugs were administered intratumorally as described below. 1) control, 2) TNF 5,000 U single administration, 3) TNF 5,000 U, intermittently administered (once/week for two weeks), 4) TNF 5,000 U, continuously administered (3/week for two weeks), 5) HuIFN-beta 50 X 10(4) IU (3/week for two weeks), and 6) combination of 4) with 5). Results of the in vitro study revealed some suppressive effects on proliferation of tumor cells on day 7 in all 13 glioma cell lines examined with 100 U/ml TNF. And also, especially in 8 of 13 cell lines, the suppression rate was more than 30%. The suppressive effects of TNF were augmented by combined use of HuIFN-beta in all cell lines, giving a range of suppression of 67.8 to 99.3%. The in vivo study revealed that the mean tumor weight ratios (control = 100%) on day 19 (the end of the experiment) were as follows; single administration of TNF: 41.3%, intermittent: 46.7%, continuous: 26.7%, HuIFN-beta: 65.9%, combination: 18.5%. Statistical analysis disclosed significant suppressive effects on tumor proliferation between the control group and 3 TNF-administered groups (single, intermittent, and continuous) and that suppression in the continuously administered group was more severe in comparison with the group given single administration. Moreover, it was suggested that combination therapy with TNF and Hu IFN-beta was more effective than a single therapy with TNF only or HuIFN-beta only. From the results described above, it was found that human recombinant TNF had some cytotoxic effects against human malignant gliomas in vitro and in vivo, although the degree of cytotoxicity was not always higher in comparison with the effects of TNF.     

Invasion of the intracranial space by a malignant odontogenic mixed tumor: Report of a case

A case of an odontogenic tumor which invaded the intracranial space from the mandible is reported. Judging from the radiographic images it was similar to a malignant tumor. The patient died 17 years after the first visit. According to the final pathological diagnosis, it was malignant odontogenic mixed tumor of low grade which did not belong to any of the WHO classification.     

A Rare Case of Biliobiliary Fistula

Abstract: Biliobiliary fistula is a rare clinical entity. The case of a 72 year old female, who presented with epigastric pain and jaundice, is detailed herein. Endoscopic retrograde cholangiopancreatography (ERCP) revealed two stones, one each in the common bile duct and the gallbladder. Continuous endoscopic nasobiliary drainage (ENBD) was performed to relieve obstructive jaundice. Further study with contrast medium administered via the ENBD tube revealed a fistula between the neck of the gallbladder and the common bile duct. The cystic duct was intact. A stone was considered to have migrated into the common bile duct through the fistula. A diagnosis of biliobiliary fistula, Corlette type I was made. However, in this particular case, a biliobiliary fistula was noted at a site below the junction of the cystic duct and common bile duct. Removal of the gallbladder stones was followed by cholecystectomy. The common bile duct was then repaired by utilizing a T-tube. No evidence of malignancy was recognized in the resected gallbladder specimen. In the one year to date since surgery, the patient has been asymptomatic and without signs of biliary disease.     

Pericardial effusion following pulmonary resection

Objective Postoperative pericardial effusion commonly occurs after open heart surgery. However, after general thoracotomy such as pulmonary resection, there have been few reports of pericardial effusion. The purpose of this study is to investigate patients with pericardial effusion following pulmonary resection.Methods: Among 2,385 patients with pulmonary resection for lung neoplasm in our institute, eight patients, whose pericardium had never been opened during the operation, developed pericardial effusion. The clinical characteristics of the eight patients were analyzed.Results: Pericardial effusion after pulmonary resection was divided into two subtypes: pericardial effusion in three patients with left thoracotomy occurring within 30 days postoperatively, and pericardial effusion in the remaining five patients with right thoracotomy occurring more than 30 days postoperatively. Pericardiotomy or pericardiocentesis was performed in three symptomatic patients, and the remaining five asymptomatic patients were treated with diuretics. Pericardial effusion disappeared in three of the five patients about 1–3 months after the conservative treatment, while, in the remaining patients, because pericardial effusion had increased gradually, pericardiocentesis was performed.Conclusion: From our experience, the treatment strategy of drainage for early pericardial effusion and diuretics for late pericardial effusion seems to be appropriate. (Jpn J Thorac Cardiovasc Surg 2006; 54:193-198)