Living donor liver transplantation for biliary atresia complicated by situs inversus: technical highlights.

Living-donor liver transplantation (LDLT) has become an established technique to treat children with end-stage liver disease. Biliary atresia (BA), one of the most common indications for liver transplantation in children, can be associated with situs inversus (SI). In the past, the presence of SI has been considered to be an absolute contraindication for liver transplantation because of the technical difficulties. Recently, some reports of successful diseased-donor liver transplantation in patients with BA complicated by SI have been published; however, few reports of that with LDLT exist. The technical difficulties involved with LDLT for such cases have not been described. Herein, we present 4 successful cases of LDLT for BA with SI. Complex anomalies associated with SI, such as a hepatic artery arising from the supraceliac aorta, a preduodenal portal vein, and absence of the retrohepatic inferior vena cava, increase the technical difficulties involved with the operation. Additional caution is required in LDLT because a living-donor graft has short vessels and the availability of vascular grafts from the donor is limited. In conclusion, LDLT for BA complicated by SI can be managed successfully with technical modifications and scrupulous attention. This series represents the largest reported group of patients with BA complicated by SI who underwent a successful LDLT procedure.     

Stereoselectivity of a potent calcium antagonist, 1-benzyl-3-pyrrolidinyl methyl 2,6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate

Four enantiomers (3a-d) of the title compound, YM-09730 (3), were synthesized by the reaction of (-)- or (+)-5-(methoxycarbonyl)-2, 6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3-carboxylic acid (1a or 1b) with (S)- or (R)-1-benzyl-3-pyrrolidinol (2a or 2b). [3H]Nitrendipine binding affinity and coronary vasodilating activity of these compounds were evaluated. The absolute configuration of the most potent enantiomer (3a) with the longest duration was unequivocally determined to be (S)-1,4-dihydropyridine-C4 and (S)-pyrrolidine-C3 (S,S) by X-ray crystallographic study on 3a X HBr as well as 3a X HCl. The configuration of 1a corresponds to R, and the other enantiomers of 3 were respectively determined by chemical correlation. The potency order of the four enantiomers was (S,S)-3a greater than (S,R)-3b greater than (R,R)-3d greater than (R,S)-3c. Latent chiral characters of nifedipine derivatives with the identical ester groups were assigned by comparison of their puckering modes of 1,4-dihydropyridine (DHP) rings with those found in 3a X HCl or 3a X HBr. On the basis of the assignment, it has been revealed that the (S)-DHP nifedipine derivatives possess the synperiplanar carbonyl group at C5. The conformational restriction may be a factor causing stereoselectivity of antagonism.     

5-HT(2) receptor-mediated phosphoinositide hydrolysis in bovine ciliary epithelium.

The serotonin 2 (5-HT(2)) receptor antagonists, MCI-9042 (Anplag) and ketanserin, have been shown to lower intraocular pressure in rabbits (1) and humans (2). The mechanism of action of these drugs has not been determined, but it is hypothesized that 5-HT(2) receptors, and possibly alpha-adrenergic receptors, (3) may regulate in part aqueous humor production via an intracellular signal transduction pathway in the ciliary body. We therefore examined whether 5-HT(2) receptors were coupled to phosphoinositide hydrolysis in an organ culture system of isolated bovine ciliary epithelium. 5-HT stimulated [(3)H]inositol phosphates ([(3)H]InsPs) accumulation in a dose-dependent manner with a maximum increase approximately twice over the basal level. The mean EC(50) value was 1.1 microM, which was calculated from four dose-response curves. The 5-HT stimulated accumulation of [(3)H]InsPs was inhibited by spiperone (5-HT(2A/1A) and dopamine 2 (D(2)) antagonists), M-1 (a major metabolite of MCI-9042), ketanserin (5-HT(2A) antagonist), SB-206553 (5- HT(2B/2C) antagonist), and mesulergine (5-HT(2C) antagonist and D(2) agonist). It was not inhibited by chlorpromazine, which is a D(2) receptor antagonist. Accordingly, our study demonstrates that 5-HT(2) receptors are coupled to phospholipase C in bovine ciliary epithelium.     

CLINICAL EVALUATION OF PERORAL CHOLANGIOSCOPY FOR BILIARY DISEASE USING NARROW BAND IMAGING

Regarding peroral cholangioscopy (POCS) for biliary disease, due to the recent appearance of a video cholangioscope that can obtain high‐quality images, it is possible to observe subtle changes of the biliary mucosa. In addition to the conventional observation method using POCS, the biliary mucosa with also observed with narrow band imaging (NBI) in one case of chronic cholangitis and four cases of extra hepatic bile duct tumor (three surgical cases). In the conventional observation method, the vessels in the surface layer of the biliary mucosa could be observed more clearly using NBI. In one case in which a tumor was observed, the irregularity of the biliary mucosa became clear on NBI, and the vessels inside a papillary tumor could also be easily observed. In another case of bile duct tumor, the conventional observation method showed a region in the proximity of the tumor where the vessels could not be seen clearly, but they could be seen clearly on NBI. In all of the cases, the bile juice was seen as red on NBI, which disturbed the observation. With POCS using NBI, it was possible to observe the vessels and irregularities in the surface layer of the biliary mucosa more clearly than with conventional observation methods.     

Clinical outcome of surgical management for patients with renal cell carcinoma involving the inferior vena cava

BACKGROUND: The objective of this study was to evaluate the clinical outcome after surgical management of renal cell carcinoma (RCC) extending to the inferior vena cava (IVC). METHODS: This study included a total of 55 patients (41 men and 14 women; mean age, 59.3 years) with RCC (39 right- and 16 left-sided tumors) involving the IVC, who underwent radical nephrectomy and tumor thrombectomy between 1983 and 2005 at a single institution in Japan. The level of thrombus was classified as follows: level I, infrahepatic; level II, intrahepatic; level III, suprahepatic; and level IV, extending to the atrium. Clinicopathological data from these patients were retrospectively reviewed to identify factors associated with survival. RESULTS: There were 11 and 18 patients who were diagnosed as having lymph node and distant metastases, respectively. Twenty-two patients had tumor thrombus in level I, 20 in level II, 10 in level III, and 3 in level IV. Pathological examinations demonstrated that 34 and 21 patients had clear cell carcinoma and non-clear cell carcinoma, respectively, 42, 9 and 4 were pT3b, pT3c and pT4, respectively, and 6, 35 and 14 were Grades 1, 2 and 3, respectively. Cancer-specific 1-, 3- and 5-year survival rates of these 55 patients were 74.5%, 51.4% and 30.3%, respectively. Among several factors examined, clinical stage (P = 0.047), lymph node metastasis (P = 0.016), histological subtype (P = 0.034) and tumor grade (P < 0.001) were significantly associated with cancer-specific survival by univariate analysis. Furthermore, multivariate analysis demonstrated clinical stage (P = 0.037) and tumor grade (P < 0.001) as independent predictors of cancer-specific survival irrespective of other significant factors identified by univariate analysis. CONCLUSIONS: In patients with RCC involving the IVC, biological aggressiveness characterized by tumor grade rather than tumor extension would have more potential prognostic importance; therefore, more intensive multimodal therapy should be considered in patients with high grade RCC with tumor thrombus extending into the IVC.     

First-line high-dose chemotherapy combined with peripheral blood stem cell transplantation for patients with advanced extragonadal germ cell tumors

BACKGROUND: The objective of this study was to evaluate the efficacy and safety of first-line high-dose chemotherapy (HDCT) combined with peripheral blood stem cell transplantation (PBSCT) for patients with advanced extragonadal germ cell tumors (EGGCT). METHODS: Six male patients with advanced non-seminomatous EGGCT were treated with HDCT combined with PBSCT following 2-3 cycles of conventional-dose induction chemotherapy. The regimens used for HDCT were carboplatin, etoposide and ifosfamide (ICE) in five patients and ICE plus paclitaxel (T-ICE) in one patient, and that for induction therapy was cisplatin, etoposide and bleomycin (PEB) in all patients. As a rule, HDCT was continuously administered until alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin normalized (beta-HCG). RESULTS: Following 1-6 courses of HDCT (median, 4 courses), beta-HCG and AFP were normalized in all patients, and five and one patient were diagnosed as showing partial remission and stable disease, respectively. Five patients underwent surgical resection of residual tumors after HDCT, yielding necrotic tissue in two, mature teratoma in two, and viable cancer tissue in one, and the surgical margin was negative in all patients. At a median follow-up of 36 months, five patients were alive and disease-free, whereas the remaining one died of disease progression. Although all patients had grade 3 hematological toxicity, there was no treatment-related death by combining PBSCT. CONCLUSIONS: First-line HDCT with PBSCT could be safely administered to patients with advanced EGGCT, and the antitumor effect of this treatment was comparatively favorable. First-line HDCT therefore may represent an attractive option for patients with advanced EGGCT.     

Endocrinology: High incidence of embryo transfer cancellations in patients with polycystic ovarian syndrome

This study was aimed at assessing the outcome of in-vitro fertilization(IVF) and embryo transfer in patients with polycystic ovariansyndrome (PCOS). The results of IVF and embryo transfer in PCOSpatients (PCOS group, 78 cycles of 26 patients) were comparedwith those of a control group (423 cycles in 202 patients withoutmale factor; age and ovarian stimulation protocol were matched).Although the pregnancy rate per transfer was not different inthe two groups of patients (25 versus 34%, PCOS versus controlgroup), the PCOS group had a significantly lower pregnancy rateper follicle aspiration (19 versus 31%, P < 0.05). A notableresult was a significantly higher incidence of embryo transfercancellations in the PCOS group (22 versus 8%, P < 0.01),which resulted from unpredictable failure of either oocyte recoveryor fertilization. The incidence of unexplained complete failureof fertilization was significantly higher in the PCOS group(18 versus 5%, P < 0.01). These results may reflect a reducedquality of the oocytes in the PCOS group, and there was a subgroupof PCOS patients who repeatedly produced poor results of treatment.Although the ovarian stimulation regimen best suited to PCOSpatients remains to be determined, special care should be takenduring ovarian stimulation, especially when the PCOS patientshad experienced unexplained failure of oocyte recovery or fertilizationin the previous treatment cycle(s).     

Clinical and pathological evaluations of methotrexate, vinblastine, Adriamycin and cisplatin chemotherapy for advanced urothelial cancers

We have treated advanced transitional-cell carcinoma of the urothelial tract with methotrexate, vinblastine, Adriamycin, and cisplatin (M-VAC) chemotherapy since July of 1985. We analyzed the effect of that chemotherapy in 26 patients with advanced urothelial cancer who were treated in our hospital and followed up. They were divided into two groups. Group 1 consisted of 15 patients with distant metastases. In all, 11 of them received M-VAC as adjuvant chemotherapy for metastatic lesions after surgical removal of the primary lesion, and the remaining 4 patients were not operable since they had very advanced-stage tumors; they received only M-VAC chemotherapy. Group 2 contained 11 patients who received M-VAC neo-adjuvant chemotherapy. In group 1, the overall response rate was 57.1% and the mean duration of response was 12.6 months. In the 11 patients who had received M-VAC as adjuvant therapy after surgical removal of the primary tumor, the mean duration of response was 14.1 months. After M-VAC chemotherapy, six patients underwent surgical resection of metastatic lesions and restaging was done pathologically in these cases. The clinical response coincided with the pathological response in all six cases. In group 2,5 of 11 patients experienced histological downstaging of the resected bladder. M-VAC chemotherapy combined with surgical resection of residual tumors has proved to be an effective option against advanced urothelial cancer.Presented at the 4th International Conference on Treatment of Urinary Tract Tumors with Adriamycin/Farmorubicin, 16–17 November 1990, Osaka, Japan