A Tissue-Engineered Artificial Bile Duct Grown to Resemble The Native Bile Duct

The aim of this study was to fabricate an artificial bile duct for the development of a new treatment for biliary diseases. Eighteen hybrid pigs were implanted with a bile duct organoid unit (BDOU) made of a bioabsorbable polymer. Twelve of the transplanted BDOUs had been seeded with autologous bone marrow cells (BMCs) in advance. Six animals, the controls, were grafted with the scaffold alone with no BMCs seeded. The common bile duct was cut, the hepatic cut end of the native common bile duct was anastomosed to the BDOU and the other end was anastomosed to the duodenum. The controls underwent a similar operation. The neo-bile duct was removed at pre-determined time points and investigated histologically. All 18 recipient pigs survived until their sacrifice at 6 weeks, 10 weeks or 6 months. Histological examination revealed incomplete epithelialization of the neo-bile duct at 6 weeks and 10 weeks after transplantation. At 6 months, the organoid exhibited a morphology almost identical to that of the native common bile duct. No differences were found between the controls and BMC-seeded pigs. These results show that the artificial bile duct thus fabricated can serve as a substitute for the native bile duct.     

ENDOSCOPIC MUCOSAL RESECTION AND SUBMUCOSAL DISSECTION METHOD FOR LARGE COLORECTAL TUMORS

The goal of endoscopic mucosal resection (EMR) is to allow the endoscopist to obtain tissue or resect lesions not previously amenable to standard biopsy or excisional techniques and to remove malignant lesions without open surgery. In this article, we describe the results of conventional EMR and EMR using an insulation‐tipped (IT) electrosurgical knife (submucosal dissection method) for large colorectal mucosal neoplasms and discuss the problems and future prospects of these procedures. At present, conventional EMR is much more feasible than EMR using IT‐knife from the perspectives of time, money, complication, and organ preservation. However, larger lesions tend to be resected in a piecemeal fashion; and it is difficult to confirm whether EMR has been complete. For accurate histopathological assessment of the resected specimen en bloc EMR is desirable although further experience is needed to establish its safety and efficacy. Further improvements of in EMR with special knife techniques are required to simply and safely remove large colorectal neoplasms.     

Sentinel node sampling limits lymphadenectomy in stage I non-small cell lung cancer.

OBJECTIVE: It is controversial whether a systematic mediastinal lymph node dissection (MLND) needs to be performed in all patients with stage I lung cancer. The present study was done to examine the new sentinel lymph nodes hypothesis based on the lobe of the primary tumor. METHODS: In our first study, the lymph node (LN) metastases were assessed in 291 stage I non-small cell lung cancer (NSCLC) patients who had a major lung resection with a systematic mediastinal lymph node dissection. We evaluated the validity of using our new sentinel lymph nodes method based on the lobe of the primary tumor as follows: the pretracheal (#3), tracheobronchial (#4), and hilar nodes (#10) for right upper lobe tumors; #4, subcarinal (#7), and #10 for middle lobe tumors; the subaortic (#5), paraaortic (#6), and #10 for left upper lobe tumors; and the #7, #10, and interlobar nodes (#11) for tumors in either lower lobes. In the second study, we performed a lobectomy with new sentinel node sampling in 64 patients with preoperative complications. If all of the sampling nodes showed no metastases on frozen section diagnosis, systematic node dissections were not performed. RESULTS: Six of 291 patients in the first study had skip metastases that did not involve the new sentinel nodes; 5 of the 6 patients had macroscopic pleural invasion. Thus, we defined pleural invasion as an exclusion criterion for the second study. In the second study, the median follow-up time was 39 months. Metastatic lymph nodes were detected in 11 of 64 patients. Fifty-three patients (83%) had no metastasis in the sampled nodes, and, therefore, a mediastinal lymph node dissection was not done. The morbidity rate in the sampling group was 36%, and there was no mortality. In the sampling group, local recurrences were observed in two patients, distant metastases in eight, and carcinomatous pleuritis in one; the overall 5-year survival rate was 82%. CONCLUSIONS: We found that it is possible to perform a less invasive lymphadenectomy for patients with stage I lung cancer using intra-operative sampling of new sentinel lymph nodes.     

Incidence and prognostic factors of Japanese breast cancer patients with bone metastasis

Background Few previous studies have analyzed the incidence of bone metastases in a defined population of Japanese breast cancer patients and their prognosis after chemotherapy. Methods This is a retrospective cohort study. We investigated 695 patients who underwent surgery for breast cancer. The strategy of adjuvant therapy was as follows. Patients with both estrogen receptors (ERs) and progesterone receptors (PgRs) had endocrine therapy as initial adjuvant therapy (n = 239). Patients with neither ERs nor PgRs had chemotherapy. When metastasis to other organs, including bone, was identified, patients received chemotherapy. The survival rates after surgery and after the onset of bone metastasis, as well as the incidence of bone metastasis, were calculated. We also evaluated the prognostic and predictive factors. Results Bone metastases developed in 148 of 695 patients. All 148 received chemotherapy, and 121 of them developed spinal metastases. The 5-year survival rate after bone metastases was 26.1%. Prognostic factors for bone metastases were visceral metastases and PgR status. Cord compression was observed in 17 of the 148 patients, with the thoracic spine being the most common. The 1-year survival rate for patients with bone metastases who received chemotherapy was 66.3%, whereas that of patients with paralysis after spinal metastases was 17.6%. Within 6 months of the development of spinal cord compression, 70.6% of the patients died. Conclusions We reported the incidence and prognostic factors for a defined population of Japanese breast cancer patients with bone and spinal metastases. Our results suggest that the expected survival time for patients with paralysis who received adequate endocrine therapy or chemotherapy is generally poor. However, to detect a predictive factor of long survival after paralysis and establish the indications for surgery, a comparative study among large groups of patients with paralysis and with different backgrounds is necessary.     

Effects of iomeprol,a new nonionic contrast medium,vis a vis iopamidol and nitroglycerin,on coronary diameter and blood flow in chronically instrumented dogs

The effects of an intracoronary administration of iomeprol, a new nonionic tri-iodinated water-soluble contrast medium, on coronary circulation were compared to those of iopamidol and those of nitroglycerin in 6 chronically instrumented conscious dogs. A pair of 10 MHz piezoelectric crystals and an electromagnetic flow probe were placed on the left circumflex coronary artery (LCCA) to measure the epicardial coronary diameter (CD) and coronary blood flow (CBF). Polyethylene tubing for drug administration was inserted into the LCCA proximal to the sonomicrometers. Iomeprol at the dose of 1 ml and 3 ml/min for 1 min significantly increased CD by 0.6±0.1% and 1.4±0.3%, respectively and CBF by 44.5±9% and 70±10%, respectively. Iopamidol at the same rates also significantly increased CD by 0.8±0.1% and 1.5±0.3% and CBF by 50±11% and 82±14%, respectively. There was no statistically significant difference between iomeprol-and iopamidol-induced increases in CD and CBF. However, the duration of the increase in CD was significantly shorter (p<0.05) after iomeprol than after iopamidol. Nitroglycerin (10 μg/kg) significantly increased CD by 4.5±1% and CBF by 105±10%. The increases in CD and CBF in response to iopamidol and iomeprol were significantly smaller (p<0.01) than to nitroglycerin. We conclude that vasodilating effects of iomeprol and iopamidol on the large epicardial coronary artery and coronary blood flow are comparable in conscious dogs and significantly lower than after nitroglycerin in the doses used by us. This study was supported by a grant from the EI-ZA1 Pharmaceutical Co., Tokyo, Japan.     

Diagnostic imaging of spinal cord lesions

Magnetic resonance imaging (MRI) has greatly facilitated morphologic evaluation of spinal cord lesions. Eleven cases representative of inflammatory, demyelinating, neoplastic and vascular diseases, are presented which illustrate and summarize important abnormal features in spinal cord imaging, particularly MR findings. Recently, specialised techniques such as MR angiography, fat-inhibiting methods, dynamic MRI and functional imaging have been developed. These methods have facilitated not only lesion diagnosis but also qualitative assessment, and are being used to analyze pathophysiology. Comprehensive diagnoses based on such modalities may be important in determining indications for surgery or defining the extent of surgery or the intensity of other treatments.     

The efficacy of fluconazole in treating prosthetic valve endocarditis caused byCandida glabrata: Report of a case

A case of active prosthetic valve infective endocarditis (PVE) due toCandida glabrata was successfully treated by the systemic administration of fluconazole. A 66-year-old Japanese man with infective endocarditis of unknown etiology underwent aortic and mitral valve replacement to treat severe aortic and mitral regurgitation associated with multiple organ failure. Postsurgical cultures of arterial blood were repeatedly positive forC. glabrata, and therefore fluconazole was administered either intravenously or orally at a dose of 400 mg/day for 46 days. During that time the signs of inflammation including fever such as an elevated white blood cell count and the presence of C-reactive protein (CRP) all improved while the blood cultures became negative. Fluconazole is thus considered to be effective in treating PVE caused byC. glabrata. When administering this treatment, it is also important to monitor the patient's renal and liver function.     

The effect of adjuvant therapy with or without tamoxifen on the endocrine function of patients with breast cancer

The ovarian and pituitary functions of 64 operable breast cancer patients undergoing adjuvant therapy with cytotoxic chemotherapy and/or tamoxifen were investigated. The post menopausal patients, divided into 3 treatment groups, one with tamoxifen alone, one with tamoxifen and chemotherapy and the other with chemotherapy alone had serum estradiol 17-β (E2) and progesterone levels lower than the evaluable limits. Although there was no significant difference in the level of estrone sulfate (E1-S) between these three groups, the level of lutainizing hormone (LH) and follicle stimulating hormone (FSH) in the patients treated with tamoxifen alone and tamoxifen and chemotherapy were significantly lower than those treated with chemotherapy alone. The decrease in gonadotropin levels induced by tamoxifen treatment was reversible as it appeared after the initiation of tamoxifen and recovered after its cessation. In the premenopausal patients, a group treated with tamoxifen and chemotherapy had significantly higher E1-S, E2 and progesterone levels and significantly lower gonadotropin levels than a group treated with chemotherapy alone or one treated with a cyclophosphamide regimen. These increases in the levels of estrogen and progesterone were also reversible, and induced by tamoxifen. Thus, adjuvant endocrinochemotherapy causes profound alteration in the hypothalamo-pituitary-ovarian axis and therefore, monitoring a variety of hormonal levels is thought to be necessary for assessing the consequences of adjuvant therapy in breast cancer patients, especially in premenopausal patients using tamoxifen.     

The possible mechanism of interaction between xanthines and quinolone

To clarify the mechanism of interaction between theophylline and enoxacin, the effects of enoxacin and its metabolite, 4-oxo-enoxacin, on the disposition of new xanthine derivatives, 1-methyl-3-propylxanthine (MPX) and 3-propylxanthine (enprofylline), as models of theophylline have been investigated in rats. Pretreatment with enoxacin significantly delayed the elimination of MPX from plasma. No significant change in the volume of distribution of MPX was observed in the presence of enoxacin, but the total body clearance of MPX was significantly decreased by approximately 60 and 80% after pretreatment with 25 and 100 mg kg-1 of enoxacin, respectively. The amount of the decrease in total body clearance depended on the dose of enoxacin. 4-Oxo-enoxacin had little or no effect on MPX disposition. A newly developed quinolone, NY-198, which does not affect the disposition of theophylline, also did not affect the disposition of MPX. Enoxacin also had no effect on the disposition of enprofylline. These results indicate that the mechanism for decrease in theophylline clearance induced by enoxacin may not be due to its metabolite, 4-oxo-enoxacin, but to enoxacin itself, and that enoxacin does not inhibit solely the elimination process depending on cytochrome P450 isoenzyme for N-demethylation. It is likely that enoxacin has no influence on the renal excretion of xanthines.