Fenestrated Fontan-like circulation under durable left-ventricular assist device support in fulminant myocarditis.

Fulminant myocarditis is a fatal development from profound biventricular heart failure and often requires both right- and left-ventricular assistance to maintain hemodynamics, even at the risk of increased mortality and morbidity. Here, we present a 42-year-old female with profound biventricular failure due to fulminant myocarditis, resolved by an isolated durable left-ventricular assist device support under a fenestrated, Fontan-like circulation and managed low-pulmonary vascular resistance.

Simultaneous detection of various pathogenic Escherichia coli in water by sequencing multiplex PCR amplicons.

Waterborne diseases due to pathogen contamination in water are a serious problem all over the world. Accurate and simultaneous detection of pathogens in water is important to protect public health. In this study, we developed a method to simultaneously detect various pathogenic Escherichia coli by sequencing the amplicons of multiplex PCR. Our newly designed multiplex PCR amplified five genes for pathogenic E. coli (uidA, stx1, stx2, STh gene, and LT gene). Additional two PCR assays (for aggR and eae) were also designed and included in the amplicon sequencing analysis. The same assays were also used for digital PCR (dPCR). Strong positive correlations were observed between the sequence read count and the dPCR results for most of the genes targeted, suggesting that our multiplex PCR-amplicon sequencing approach could provide quantitative information. The method was also successfully applied to monitor the level of pathogenic E. coli in river water and wastewater samples. The approach shown here could be expanded by targeting genes for other pathogens.

Large-scale genome analysis of bovine commensal Escherichia coli reveals that bovine-adapted E. coli lineages are serving as evolutionary sources of the emergence of human intestinal pathogenic strains.

How pathogens evolve their virulence to humans in nature is a scientific issue of great medical and biological importance. Shiga toxin (Stx)-producing Escherichia coli (STEC) and enteropathogenic E. coli (EPEC) are the major foodborne pathogens that can cause hemolytic uremic syndrome and infantile diarrhea, respectively. The locus of enterocyte effacement (LEE)-encoded type 3 secretion system (T3SS) is the major virulence determinant of EPEC and is also possessed by major STEC lineages. Cattle are thought to be the primary reservoir of STEC and EPEC. However, genome sequences of bovine commensal E. coli are limited, and the emerging process of STEC and EPEC is largely unknown. Here, we performed a large-scale genomic comparison of bovine commensal E. coli with human commensal and clinical strains, including EPEC and STEC, at a global level. The analyses identified two distinct lineages, in which bovine and human commensal strains are enriched, respectively, and revealed that STEC and EPEC strains have emerged in multiple sublineages of the bovine-associated lineage. In addition to the bovine-associated lineage-specific genes, including fimbriae, capsule, and nutrition utilization genes, specific virulence gene communities have been accumulated in stx- and LEE-positive strains, respectively, with notable overlaps of community members. Functional associations of these genes probably confer benefits to these E. coli strains in inhabiting and/or adapting to the bovine intestinal environment and drive their evolution to highly virulent human pathogens under the bovine-adapted genetic background. Our data highlight the importance of large-scale genome sequencing of animal strains in the studies of zoonotic pathogens.

Surgical outcomes of bridge-to-bridge therapy with extracorporeal left ventricular assist device for acute myocardial infarction in cardiogenic shock.

BACKGROUND: Extracorporeal left ventricular assist device is often required for acute myocardial infarction patients in cardiogenic shock when temporary mechanical circulatory support fails to provide hemodynamic stabilization. This study aimed to evaluate the clinical outcomes of acute myocardial infarction patients in cardiogenic shock supported by an extracorporeal left ventricular assist device. METHODS: This retrospective study enrolled 13 acute myocardial infarction patients in cardiogenic shock treated with an extracorporeal left ventricular assist device from April 2011 to July 2020. RESULTS: Twelve (92.3%) and eleven (84.6%) patients were supported using venoarterial extracorporeal membrane oxygenation and intra-aortic balloon pumping before implantation, respectively. The median duration from acute myocardial infarction to extracorporeal left ventricular assist device implantation was 7 (3.5-24.5) days. The overall in-hospital mortality rate was 30.8% (n = 4). Extracorporeal left ventricular assist device was explanted in one patient for cardiac recovery; eight (61.5%) patients were approved as heart transplant candidates in whom the extracorporeal left ventricular assist device was exchanged for a durable left ventricular assist device; two (15.4%) expired while waiting for a heart transplant, and two (15.4%) received a successful transplant. The 1- and 3-year overall survival rates after extracorporeal left ventricular assist device implantation were 68.3% and 49.9%, respectively. CONCLUSIONS: The operative mortality after extracorporeal left ventricular assist device implantation in acute myocardial infarction patients in cardiogenic shock was favorable. Our strategy of early hemodynamic stabilization with extracorporeal left ventricular assist device implantation in these patients as a bridge-to-bridge therapy was effective in achieving better survival.

Validity of Ipsilateral Internal Mammary Coronary Artery Bypass Graft of Arteriovenous Fistula.

BACKGROUND: In coronary artery bypass grafting (CABG) for haemodialysis patients, arteriovenous fistula can reduce blood flow from the internal mammary artery (IMA) graft. The purpose of this study was to delineate the rationale of ipsilateral IMA grafting to the arteriovenous fistula by assessing graft flow and patency. METHOD: The clinical records of 139 haemodialysis patients who underwent off-pump CABG, including IMA grafting to the left anterior descending artery (LAD) between April 2007 and December 2018, were retrospectively reviewed. Clinical outcomes and transit-time flowmetry results of IMA to LAD bypass grafts during off-pump CABG and postoperative angiography were examined. RESULTS: An ipsilateral IMA to the arteriovenous fistula (Ipsi-IMA) was used in 89 patients, and a contralateral IMA to the arteriovenous fistula (Contra-IMA) was used in 50 patients and no hospital deaths occurred. The mean graft flow and angiographic patency rate did not differ between the Ipsi-IMA and Contra-IMA groups. In patients with 51 to 90% stenosis of LAD, there was no significant difference in the mean graft flow. In comparison, in the patients with 91 to 100% stenosis of LAD, the mean graft flow in the Ipsi-IMA group was significantly lower than that in the Contra-IMA group (p=0.03). Kaplan-Meier analyses showed a 5-year survival rate of 57.6% for Ipsi-IMA and 64.8% for Contra-IMA (p=0.47). CONCLUSIONS: In the revascularisation of the LAD, the graft patency rate of the Ipsi-IMA was not inferior to that of the Contra-IMA. However, when the LAD has 91 to 100% stenosis, a Contra-IMA to arteriovenous fistula may be beneficial in terms of sufficient flow capacity.

Whole-Genome Sequencing of Shiga Toxin-Producing Escherichia coli OX18 from a Fatal Hemolytic Uremic Syndrome Case.

We report a fatal case of hemolytic uremic syndrome with urinary tract infection in Japan caused by Shiga toxin-producing Escherichia coli. We genotypically identified the isolate as OX18:H2. Whole-genome sequencing revealed 3 potentially pathogenic lineages (OX18:H2, H19, and H34) that have been continuously isolated in Japan.

Distribution of Novel Og Types in Shiga Toxin-Producing Escherichia coli Isolated from Healthy Cattle.

Shiga toxin-producing Escherichia coli (STEC) is an important foodborne pathogen. Although most cases of STEC infection in humans are due to O157 and non-O157 serogroups, there are also reports of infection with STEC strains that cannot be serologically classified into any O serogroup (O-serogroup untypeable [OUT]). Recently, it has become clear that even OUT strains can be subclassified based on the diversity of O-antigen biosynthesis gene cluster (O-AGC) sequences. Cattle are thought to be a major reservoir of STEC strains belonging to various serotypes; however, the internal composition of OUT STEC strains in cattle remains unknown. In this study, we screened 366 STEC strains isolated from healthy cattle by using multiplex PCR kits including primers that targeted novel O-AGC types (Og types) found in OUT E. coli and Shigella strains in previous studies. Interestingly, 94 (25.7%) of these strains could be classified into 13 novel Og types. Genomic analysis revealed that the results of the in silico serotyping of novel Og-type strains were perfectly consistent with those of the PCR experiment. In addition, it was revealed that a dual Og8+OgSB17-type strain carried two types of O-AGCs from E. coli O8 and Shigella boydii type 17 tandemly inserted at the locus, with both antigens expressed on the cell surface. The results of this comprehensive analysis of cattle-derived STEC strains may help improve our understanding of the strains circulating in the environment. Additionally, the DNA-based serotyping systems used in this study could be used in future epidemiological studies and risk assessments of other STEC strains.

Early and mid-term results of transcatheter aortic valve implantation and valve durability assessment.

This study aimed to evaluate the early and mid-term outcomes of transcatheter aortic valve implantation (TAVI) and to assess valve durability. A total of 146 consecutive patients who underwent TAVI for severe aortic stenosis between October 2013 and August 2018 were retrospectively reviewed. All patients (mean age, 84 ± 6 years; age range 53-98 years; 42 males [28.7%]) had multiple comorbidities, with a mean logistic EuroSCORE of 30.9 ± 17.4%. Eighteen patients (12.3%) were aged 90 years or over. Five in-hospital deaths (3.4%) occurred, and 36 patients (24.7%) experienced major TAVI-related complications. With the transfemoral approach, 10 patients had major vascular complications, which mostly occurred with first-generation devices (n = 9) but less commonly with new-generation low-profile devices (P = 0.0078). During a follow-up period of 580 ± 450 (11-1738) days, 29 late deaths occurred. The survival rate was 86.0%, 78.0%, and 61.7% at 1, 2, and 3 years, respectively. Multivariate Cox hazard regression analysis revealed that more-than-moderate tricuspid regurgitation was the only independent risk factor for late deaths due to any cause (hazard ratio, 3.145; 95% confidence interval, 1.129-8.762; P = 0.0283). No statistically significant differences between post-TAVI before discharge from the hospital and at 4 years after TAVI were observed with respect to aortic valve area (1.76 ± 0.49 cm2 vs. 1.64 ± 0.38 cm2; P = 0.1871) and mean pressure gradient (10.0 ± 4.6 mmHg vs. 7.9 ± 3.3 mmHg; P = 0.5032). TAVI was a feasible method with acceptable early and mid-term outcomes and valve durability for at least 4 years in poor-risk patients. Further close follow-up is essential to evaluate late outcomes and valve durability.

Additional Og-Typing PCR Techniques Targeting Escherichia coli-Novel and Shigella-Unique O-Antigen Biosynthesis Gene Clusters.

The O-serogrouping of pathogenic Escherichia coli is a standard method for subtyping strains for epidemiological studies and controls. O-serogroup diversification shows a strong association with the genetic diversity in some O-antigen biosynthesis gene clusters. Through genomic studies, in addition to the types of O-antigen biosynthesis gene clusters (Og-types) from conventional O-serogroup strains, a number of novel Og-types have been found in E. coli isolates. To assist outbreak investigations and surveillance of pathogenic E. coli at inspection institutes, in previous studies, we developed PCR methods that could determine almost all conventional O-serogroups and some novel Og-types. However, there are still many Og-types that may not be determined by simple genetic methods such as PCR. Thus, in the present study, we aimed to develop an additional Og-typing PCR system. Based on the novel Og-types, including OgN32, OgN33, and OgN34, presented in this study, we designed an additional 24 PCR primer pairs targeting 14 novel and 2 diversified E. coli Og-types and 8 Shigella-unique Og-types. Subsequently, we developed 5 new multiplex PCR sets consisting of 33 primers, including the aforementioned 24 primers and 9 primers reported in previous studies. The accuracy and specificity of the PCR system was validated using approximately 260 E. coli and Shigella O-serogroup and Og-type reference strains. The Og-typing PCR system reported here can determine a wide range of Og-types of E. coli and may help epidemiological studies, in addition to the surveillance of pathogenic E. coli.

Development of a High-Efficacy Reprogramming Method for Generating Human Induced Pluripotent Stem (iPS) Cells from Pathologic and Senescent Somatic Cells.

Induced pluripotent stem (iPS) cells are a type of artificial pluripotent stem cell induced by the epigenetic silencing of somatic cells by the Yamanaka factors. Advances in iPS cell reprogramming technology will allow aging or damaged cells to be replaced by a patient's own rejuvenated cells. However, tissue that is senescent or pathologic has a relatively low reprogramming efficiency as compared with juvenile or robust tissue, resulting in incomplete reprogramming; iPS cells generated from such tissue types do not have sufficient differentiation ability and are therefore difficult to apply clinically. Here, we develop a new reprogramming method and examine it using myofibroblasts, which are pathologic somatic cells, from patient skin tissue and from each of the four heart chambers of a recipient heart in heart transplant surgery. By adjusting the type and amount of vectors containing transcriptional factors for iPS cell reprogramming, as well as adjusting the transfection load and culture medium, the efficiency of iPS cell induction from aged patient skin-derived fibroblasts was increased, and we successfully induced iPS cells from myocardial fibroblasts isolated from the pathologic heart of a heart transplant recipient.

Escherichia coli H-Genotyping PCR: a Complete and Practical Platform for Molecular H Typing.

In Escherichia coli, more than 180 O groups and 53 H types have been recognized. The O:H serotyping of E. coli strains is an effective method for identifying strains with pathogenic potential and classifying them into clonal groups. In particular, the serotyping of Shiga toxin-producing E. coli (STEC) strains provides valuable information to evaluate the routes, sources, and prevalence of agents in outbreak investigations and surveillance. Here, we present a complete and practical PCR-based H-typing system, E. coli H-genotyping PCR, consisting of 10 multiplex PCR kits with 51 single PCR primer pairs. Primers were designed based on a detailed comparative analysis of sequences from all H-antigen (flagellin)-encoding genes, fliC and its homologs. The specificity of this system was confirmed by using all H type reference strains. Additionally, 362 serotyped wild strains were also used to evaluate its practicality. All 277 H-type-identified isolates gave PCR products that corresponded to the results of serological H typing. Moreover, 76 nonmotile and nine untypeable strains could be successfully subtyped into any H type by the PCR system. The E. coli H-genotyping PCR developed here allows broader, rapid, and low-cost subtyping of H types and will assist epidemiological studies as well as surveillance of pathogenic E. coli.

Bacterial flora analysis of coliforms in sewage, river water, and ground water using MALDI-TOF mass spectrometry.

The aim of this study was to rapidly and effectively analyze coliforms, which are the most fundamental indicators of water quality for fecal pollution, using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). Coliform bacteria were isolated from municipal sewage, river water, and groundwater. For each sample, 100 isolates were determined by MALDI-TOF MS. In addition, these same 100 isolates were also identified via 16S rRNA gene sequence analysis. Obtained MALDI-TOF MS data were compared with the 16S rRNA sequencing analysis, and the validity of MALDI-TOF MS for classification of coliform bacteria was examined. The concordance rate of bacterial identification for the 100 isolates obtained by MALDI-TOF MS analysis and 16S rRNA gene sequence analysis for sewage, river water, and ground water were 96%, 74%, and 62% at the genus level, respectively. Among the sewage, river water, and ground water samples, the coliform bacterial flora were distinct. The dominant genus of coliforms in sewage, river water, and groundwater were Klebsiella spp., Enterobacter spp., and Serratia spp., respectively. We determined that MALDI-TOF MS is a rapid and accurate tool that can be used to identify coliforms. Therefore, without using conventional 16S rRNA sequencing, it is possible to rapidly and effectively classify coliforms in water using MALDI-TOF MS.

Enteropathogenic Escherichia coli O80:H2 in Young Calves with Diarrhea, Belgium.

Serogroup O80 was detected in 40% of 104 enteropathogenic Escherichia coli isolates from calves with diarrhea from 42 farms in Belgium during 2008‒2015. These isolates harbored the eae-ξ and fliCH2 genes, similar to the O80 attaching-effacing Shigatoxigenic E. coli isolates found in humans in France. This strain might be emerging.

Radiologic-Pathologic Correlation of Primary and Secondary Cardiomyopathies: MR Imaging and Histopathologic Findings in Hearts from Autopsy and Transplantation.

Cardiac magnetic resonance (MR) imaging with late gadolinium enhancement (LGE) is used to detect and assess the myocardial damage seen with a variety of cardiomyopathies. Gadolinium-based contrast material accumulates in the expanded interstitial space of the myocardium. Areas with LGE correspond to replacement fibrosis, fibrofatty change, epithelioid granuloma, inflammatory cell infiltration, cardiomyocyte necrosis, and amyloid deposition-conditions that represent a focal increase in interstitial space. Areas without LGE correspond to interstitial or plexiform fibrosis, mildly degenerated cardiomyocytes, inflammatory cell infiltration, and diffuse amyloid deposition-conditions that represent diffuse increases in interstitial space. LGE MR imaging cannot depict these diffuse changes and does not enable quantitative evaluation of this increased interstitial space because on inversion-recovery MR images, the inversion time is adjusted to null the signal from normal-appearing or the least enhancing regions of the myocardium. Thus, the absence of LGE does not always indicate normal myocardial tissue. The use of current T1 mapping techniques enables one to overcome these drawbacks of LGE imaging, detect diffuse myocardial abnormalities, and perform quantitative analysis of the interstitial space. The authors describe the histopathologic and corresponding cardiac MR imaging findings of hypertrophic cardiomyopathy, dilated cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, cardiac sarcoidosis, giant cell myocarditis, and cardiac amyloidosis-mainly those seen on LGE MR images-as assessed by using whole-heart specimens obtained from autopsy or transplantation. ©RSNA, 2017.

[Re-operation for Saccular Aneurysm after Ascending Aortic Replacement with Homograft;Report of a Case].

A 62-years-old female had undergone ascending aortic replacement with homograft for graft infection and mediastinitis after initial replacement of ascending aorta due to acute type A dissection. Ten years after homograft replacement, follow up computed tomography showed acute growing saccular aneurysm of the homograft without infectious symptoms. We urgently performed Bentall procedure and hemiarch replacement successfully. Pathological diagnosis was true aneurysm of the homograft. She was discharged from hospital without any complication and has been quite uneventful 7 years after surgery. True aneurysm of the homograft is very rare and our case is the 1st report of successful reoperation.

Secondary Shiga Toxin-Producing Escherichia coli Infection, Japan, 2010-2012.

To evaluate the potential public health risk caused by secondary Shiga toxin-producing Escherichia coli (STEC) infections in Japan, we investigated the prevalence and characteristics of STEC isolated from healthy adults during 2010-2012. Although prevalence among healthy adults was high, most STEC organisms displayed characteristics rarely found in isolates from symptomatic patients.

Phylogenetic Analysis of Enteroaggregative Escherichia coli (EAEC) Isolates from Japan Reveals Emergence of CTX-M-14-Producing EAEC O25:H4 Clones Related to Sequence Type 131.

Enteroaggregative Escherichia coli (EAEC) causes acute or persistent diarrhea. The aggR gene is widely used as a marker for typical EAEC. The heterogeneity of EAEC is well known; however, there are few reports on the phylogenetic relationships of EAEC. Recently, CTX-M extended-spectrum ß-lactamase (ESBL)-producing EAEC strains have been reported worldwide. To characterize EAEC strains in Japan, we investigated the population structure of EAEC. A total of 167 aggR-positive strains isolated from stool specimens from diarrheal patients in Kagoshima (139 strains) and Osaka (28 strains), Japan, between 1992 and 2010 were examined for the prevalence of EAEC virulence markers, the blaCTX-M gene, and the capacity to form biofilms. Multilocus sequence typing was also conducted. EAEC strains were widely distributed across four major E. coli phylogroups. Strains of O111:H21/clonal group 40 (CG40) (30 strains), O126:H27/CG200 (13 strains), and O86a:H27/CG3570 (11 strains) in phylogroup B1 are the historical EAEC clones in Japan, and they exhibited strong biofilm formation. Twenty-nine strains of EAEC O25:H4/CG131 were identified in phylogroup B2, 79% of which produced CTX-M-14. This clone has emerged since 2003. The clone harbored plasmid-encoded EAEC virulence genes but not chromosomal virulence genes and had lower biofilm-forming capacity than historical EAEC strains. This clone most likely emerged from a pandemic uropathogenic O25:H4/sequence type 131 clone by acquiring an EAEC virulence plasmid from canonical EAEC. Surveillance of the horizontal transfer of both virulence and ESBL genes among E. coli strains is important for preventing a worldwide increase in antimicrobial drug resistance.

Escherichia coli O-Genotyping PCR: a Comprehensive and Practical Platform for Molecular O Serogrouping.

The O serogrouping of pathogenic Escherichia coli is a standard method for subtyping strains for epidemiological studies and enhancing phylogenetic studies. In particular, the identification of strains of the same O serogroup is essential in outbreak investigations and surveillance. In a previous study, we analyzed the O-antigen biosynthesis gene cluster in all known E. coli O serogroups (A. Iguchi et al., DNA Res, 22:101-107, 2015, http://dx.doi.org/10.1093/dnares/dsu043). Based on those results, we have arranged 162 PCR primer pairs for the identification or classification of O serogroups. Of these, 147 pairs were used to identify 147 individual O serogroups with unique O-antigen biosynthesis genes, and the other 15 pairs were used to identify 15 groups of strains (Gp1 to Gp15). Each of these groups consisted of strains with identical or very similar O-antigen biosynthesis genes, and the groups represented a total of 35 individual O serogroups. We then used the 162 primer pairs to create 20 multiplex PCR sets. Each set contained six to nine primer pairs that amplify products of markedly different sizes. This genetic methodology (E. coli O-genotyping PCR) allowed for comprehensive, rapid, and low-cost typing. Validation of the PCR system using O-serogroup references and wild strains showed that the correct O serogroups were specifically and accurately identified for 100% (182/182) and 90.8% (522/575) of references and wild strains, respectively. The PCR-based system reported here might be a promising tool for the subtyping of E. coli strains for epidemiological studies as well as for the surveillance of pathogenic E. coli during outbreaks.

Rapid and Easy In Silico Serotyping of Escherichia coli Isolates by Use of Whole-Genome Sequencing Data.

Accurate and rapid typing of pathogens is essential for effective surveillance and outbreak detection. Conventional serotyping of Escherichia coli is a delicate, laborious, time-consuming, and expensive procedure. With whole-genome sequencing (WGS) becoming cheaper, it has vast potential in routine typing and surveillance. The aim of this study was to establish a valid and publicly available tool for WGS-based in silico serotyping of E. coli applicable for routine typing and surveillance. A FASTA database of specific O-antigen processing system genes for O typing and flagellin genes for H typing was created as a component of the publicly available Web tools hosted by the Center for Genomic Epidemiology (CGE) (www.genomicepidemiology.org). All E. coli isolates available with WGS data and conventional serotype information were subjected to WGS-based serotyping employing this specific SerotypeFinder CGE tool. SerotypeFinder was evaluated on 682 E. coli genomes, 108 of which were sequenced for this study, where both the whole genome and the serotype were available. In total, 601 and 509 isolates were included for O and H typing, respectively. The O-antigen genes wzx, wzy, wzm, and wzt and the flagellin genes fliC, flkA, fllA, flmA, and flnA were detected in 569 and 508 genome sequences, respectively. SerotypeFinder for WGS-based O and H typing predicted 560 of 569 O types and 504 of 508 H types, consistent with conventional serotyping. In combination with other available WGS typing tools, E. coli serotyping can be performed solely from WGS data, providing faster and cheaper typing than current routine procedures and making WGS typing a superior alternative to conventional typing strategies.

A case of metastatic renal cell carcinoma and bile duct carcinoma treated with a combination of sunitinib and gemcitabine.

BACKGROUND: Metastatic renal cell carcinoma (mRCC) had been a chemo-refractory disease, but recent advances in multiple kinase inhibitors such as sunitinib have dramatically changed the clinical course of mRCC. Sunitinib is used for mRCC chemotherapy based on the favorable results of a recent clinical trial, but specific biomarkers predicting efficacy and safety are not yet available. Locally advanced bile duct carcinoma (BDC) has generally been treated with single agent gemcitabine or as doublet therapy with cisplatin. Concomitant occurrence of mRCC and BDC is extremely rare, and a standard therapeutic strategy has not been established. CASE PRESENTATION: A 65-year-old woman was diagnosed as having multiple mRCC and intercurrent, locally advanced BDC. A single course of combination therapy with sunitinib (25 mg/day, day2-15) and gemcitabine (750 mg/m(2), days 1, 8) was administered, and this showed obvious effects, with partial response for mRCC and stable disease for BDC. However, the patient also experienced severe adverse events, including hematological and various non-hematological toxicities; the combination therapy was then terminated on day 13 after its initiation. She recovered on day 28 and is alive 3.5 years after the diagnosis. The plasma trough levels of sunitinib and its active metabolite SU12662 on day 13 were 91.5 ng/mL and 19.2 ng/mL, respectively, which were relatively higher than in previous reports. Analysis of her single nucleotide polymorphisms (SNPs) detected TC in ABCB1 3435C/T, TC in 1236C/T and TT in 2677G/T, suggesting a possible TTT haplotype. CONCLUSION: A rare case of double cancer of mRCC and BDC was treated by combination chemotherapy. Although unknown synergistic mechanisms of these agents may be involved, severe toxicities might be possibly associated with high sunitinib exposure. Further exploration of combination therapy with sunitinib and gemcitabine is required.