Orally Administrated Hydrogel Harnessing Intratumoral Microbiome and Microbiota-Related Immune Responses for Potentiated Colorectal Cancer Treatment.

The intestinal and intratumoral microbiota are closely associated with tumor progression and response to antitumor treatments. The antibacterial or tumor microenvironment (TME)-modulating approaches have been shown to markedly improve antitumor efficacy, strategies focused on normalizing the microbial environment are rarely reported. Here, we reported the development of an orally administered inulin-based hydrogel with colon-targeting and retention effects, containing hollow MnO2 nanocarrier loaded with the chemotherapeutic drug Oxa (Oxa@HMI). On the one hand, beneficial bacteria in the colon specifically metabolized Oxa@HMI, resulting in the degradation of inulin and the generation of short-chain fatty acids (SCFAs). These SCFAs play a crucial role in modulating microbiota and stimulating immune responses. On the other hand, the hydrogel matrix underwent colon microbiota-specific degradation, enabling the targeted release of Oxa and production of reactive oxygen species in the acidic TME. In this study, we have established, for the first time, a microbiota-targeted drug delivery system Oxa@HMI that exhibited high efficiency in colorectal cancer targeting and colon retention. Oxa@HMI promoted chemotherapy efficiency and activated antitumor immune responses by intervening in the microbial environment within the tumor tissue, providing a crucial clinical approach for the treatment of colorectal cancer that susceptible to microbial invasion.

Electrically activated polymetallic nanocrystals for long-term tumor suppression via oxygen-independent ROS generation and electro-immunotherapy.

The low oxidation level and immunosuppressive microenvironment within hypoxic tumor tissue are critical factors contributing to the inefficacy of various anti-tumor strategies. Herein, we have designed a novel intravenous injection nanoplatform to conduct electro-immunotherapy, based on phospholipid-modified PtPd nanocrystals loaded with the immunoregulator IPI549 (LP@Pt-Pd@IPI549 nanoparticles, LPPI). LPPI responds to reactive oxygen species (ROS), triggering a cascade of therapeutic effects that overcome hypoxia-related resistance and effectively eradicate hypoxic tumors. Firstly, under electric field exposure, LPPI relied on water rather than oxygen to generate abundant ROS under hypoxic conditions for tumor electrodynamic therapy (EDT). Moreover, the generated ROS further induced the disintegration of the outer phospholipid membrane of LPPI, leading to the release of the immunoregulator and inhibition of myeloid-derived suppressor cells (MDSCs), triggering cascade immune responses. Additionally, the immunomodulatory effects of IPI549, in synergy with the immunogenic cell death (ICD) induced by EDT, reversed the immunosuppressive microenvironment contributing to tumor resistance. In summary, EDT transiently killed tumor cells while simultaneously generating antigen release, instigating an adaptive immune response for electro-immunotherapy, resulting in a potent and long-lasting tumor inhibition effect.

Temporal trends in the prevalence and death of ischemic heart disease in women of childbearing age from 1990 to 2019: a multilevel analysis based on the Global Burden of Disease Study 2019.

Background: Our objective is to describe the current prevalence and death of ischemic heart disease (IHD) in women of childbearing age (WCBA) at the global, regional, and national levels and to analyze its temporal trends from 1990 to 2019. Methods: WCBA was defined as women aged 15-49 years. Estimates and 95% Uncertainty Intervals (UI) of IHD prevalence and death numbers for seven age groups were extracted from the 2019 Global Burden of Disease Study. The age-standardized prevalence and death rate (ASPR and ASDR) of IHD in WCBA was estimated using the direct age-standardization method. Joinpoint regression analysis was used to calculate average annual percent change (AAPC) to represent the temporal trends from 1990 to 2019. Results: Between 1990 and 2019, the global ASPR of IHD experienced a 3.21% increase, culminating in 367.21 (95% UI, 295.74-430.16) cases per 100,000 individuals. Conversely, the ASDR decreased to 11.11 (95% UI, 10.10-12.30) per 100,000 individuals. In 2019, among the five sociodemographic index (SDI) regions, the highest ASPR was observed in the high-middle SDI region, whereas the highest ASDR was found in the low-middle SDI region. Regionally, the Caribbean reported the highest ASPR (563.11 per 100,000 individuals; 95% UI, 493.13-643.03), and Oceania reported the highest ASDR (20.20 per 100,000 individuals; 95% UI, 13.01-31.03). At the national level, Trinidad and Tobago exhibited the highest ASPR (730.15 per 100,000 individuals; 95% UI, 633.96-840.13), and the Solomon Islands had the highest ASDR (77.77 per 100,000 individuals; 95% UI, 47.80-121.19). Importantly, over the past three decades, the global ASPR has seen a significant increase [AAPC = 0.11%, 95% Confidence Interval (CI): 0.09-0.13; P < 0.001], while the ASDR has demonstrated a significant decreasing trend (AAPC = -0.86%, 95% CI: -1.11 to -0.61; P < 0.001). Air pollution, tobacco use, high systolic blood pressure, elevated body mass index, dietary risks, and high LDL cholesterol have been identified as the leading six risk factors for IHD-related deaths among WCBA in 2019. Conclusions: Despite the significant decline in the global ASDR for IHD among WCBA over the last thirty years, the ASPR continues to escalate. We need to remain vigilant about the increased burden of IHD in WCBA. It calls for aggressive prevention strategies, rigorous control of risk factors, and the enhancement of healthcare coverage to mitigate the disease burden of IHD among WCBA in forthcoming years.

Subcutaneous implantation of nodular goiter after transoral endoscopic thyroidectomy vestibular approach: A case study and review of literature.

BACKGROUND: Extrathyroid implantation or dissemination of thyroid tissue secondary to a thyroid procedure is rare. Most of these belonged to thyroid carcinoma with metastatic potential and uncommon for benign pathologies. METHODS: We report the case of a 31-year-old female who was identified to have multiple subcutaneous implantation of thyroid tissue 5 years after transoral endoscopic thyroidectomy vestibular approach. A comprehensive literature search on implantation of thyroid tissue secondary to thyroid procedures was performed. RESULTS: Accidental tearing of the capsule during previous surgery may lead to the subcutaneous implantation. Through literature review, a total 29 articles with 47 patients were identified. 33.3% were benign lesions, and implantation was mostly secondary to fine needle aspiration biopsy (46.5%). CONCLUSIONS: Subcutaneous or port site implantation after endoscopic thyroid surgery may occur in benign thyroid pathologies and therefore, oncologic principles must be strictly followed during surgery regardless of its histopathological nature.

Deep spatial proteomics reveals region-specific features of severe COVID-19-related pulmonary injury.

As a primary target of severe acute respiratory syndrome coronavirus 2, lung exhibits heterogeneous histopathological changes following infection. However, comprehensive insight into their protein basis with spatial resolution remains deficient, which hinders further understanding of coronavirus disease 2019 (COVID-19)-related pulmonary injury. Here, we generate a region-resolved proteomic atlas of hallmark pathological pulmonary structures by integrating histological examination, laser microdissection, and ultrasensitive proteomics. Over 10,000 proteins are quantified across 71 post-mortem specimens. We identify a spectrum of pathway dysregulations in alveolar epithelium, bronchial epithelium, and blood vessels compared with non-COVID-19 controls, providing evidence for transitional-state pneumocyte hyperplasia. Additionally, our data reveal the region-specific enrichment of functional markers in bronchiole mucus plugs, pulmonary fibrosis, airspace inflammation, and alveolar type 2 cells, uncovering their distinctive features. Furthermore, we detect increased protein expression associated with viral entry and inflammatory response across multiple regions, suggesting potential therapeutic targets. Collectively, this study provides a distinct perspective for deciphering COVID-19-caused pulmonary dysfunction by spatial proteomics.

Systematic analysis of the cuprotosis in tumor microenvironment and prognosis of gastric cancer.

Cuprotosis is a new programmed cell death related to cancer. However, the characteristics of cuprotosis in gastric cancer (GC) remain unknown. Ten cuprotosis molecules from 1544 GC patients were used to identify three GC molecular genotypes. Cluster A was characterized by the best clinical outcome and was significantly enriched in metabolic signaling pathways. Cluster B exhibited elevated immune activation, high immune stroma scores and was significantly enriched in tumor immune signaling pathways. Cluster C was characterized by severe immunosuppression and poor response to immunotherapy. Notably, the citrate cycle, cell cycle, and p53 signaling pathways were enriched in the differentially expressed genes among the three subtypes, which were critical signaling pathways for cell death. We also developed a cuprotosis signature risk score that could accurately predict the survival, immunity, and subtype of GC. This study presents a systematic analysis of cuprotosis molecules and provides new immunotherapeutic targets for GC patients.

A bat MERS-like coronavirus circulates in pangolins and utilizes human DPP4 and host proteases for cell entry.

It is unknown whether pangolins, the most trafficked mammals, play a role in the zoonotic transmission of bat coronaviruses. We report the circulation of a novel MERS-like coronavirus in Malayan pangolins, named Manis javanica HKU4-related coronavirus (MjHKU4r-CoV). Among 86 animals, four tested positive by pan-CoV PCR, and seven tested seropositive (11 and 12.8%). Four nearly identical (99.9%) genome sequences were obtained, and one virus was isolated (MjHKU4r-CoV-1). This virus utilizes human dipeptidyl peptidase-4 (hDPP4) as a receptor and host proteases for cell infection, which is enhanced by a furin cleavage site that is absent in all known bat HKU4r-CoVs. The MjHKU4r-CoV-1 spike shows higher binding affinity for hDPP4, and MjHKU4r-CoV-1 has a wider host range than bat HKU4-CoV. MjHKU4r-CoV-1 is infectious and pathogenic in human airways and intestinal organs and in hDPP4-transgenic mice. Our study highlights the importance of pangolins as reservoir hosts of coronaviruses poised for human disease emergence.

An antigen processing and presentation signature for prognostic evaluation and immunotherapy selection in advanced gastric cancer.

Objective: The aim of the study was to propose a signature based on genes associated with antigen processing and presentation (APscore) to predict prognosis and response to immune checkpoint inhibitors (ICIs) in advanced gastric cancer (aGC). Background: How antigen presentation-related genes affected the immunotherapy response and whether they could predict the clinical outcomes of the immune checkpoint inhibitor (ICI) in aGC remain largely unknown. Methods: In this study, an aGC cohort (Kim cohort, RNAseq, N=45) treated by ICIs, and 467 aGC patients from seven cohorts were conducted to investigate the value of the APscore predicting the prognosis and response to ICIs. Subsequently, the associations of the APscore with the tumor microenvironment (TME), molecular characteristics, clinical features, and somatic mutation variants in aGC were assessed. The area under the receiver operating characteristic curve (AUROC) of the APscore was analyzed to estimate response to ICIs. Cox regression or Log-rank test was used to estimate the prognosis of aGC patients. Results: The APscore constructed by principal component analysis algorithms was an effective predictive biomarker of the response to ICIs in the Kim cohort and 467 aGC patients (Kim: AUC =0.85, 95% CI: 0.69-1.00; 467 aGC: AUC =0.69, 95% CI: 0.63-0.74). The APscore also was a prognostic biomarker in 467 aGC patients (HR=1.73, 95% CI: 1.21-2.46). Inhibitory immunity, decreased TMB and low stromal scores were observed in the high APscore group, while activation of immunity, increased TMB, and high stromal scores were observed in the low APscore group. Next, we evaluated the value of several central genes in predicting the prognosis and response to ICIs in aGC patients, and verified them using immunogenic, transcriptomic, genomic, and multi-omics methods. Lastly, a predictive model built successfully discriminated patients with vs. without immunotherapy response and predicted the survival of aGC patients. Conclusions: The APscore was a new biomarker for identifying high-risk aGC patients and patients with responses to ICIs. Exploration of the APscore and hub genes in multi-omics GC data may guide treatment decisions.

Expression and clinical significance of CD31, CD34, and CD105 in pulmonary ground glass nodules with different vascular manifestations on CT.

Blood vessel passage on CT exerts a vital part in early diagnosis as well as treatment of carcinoma of the lungs. Intratumoral microvascular density (iMVD) has gradually become the focus of research on biological behavior, appearance, and evolution of malignant tumors nowadays. The aim of this paper was to verify whether there is a correlation between the iMVD and the vascular morphology of ground glass nodules (GGNs). A total of 109 patients with pulmonary GGN were classified into three groups (I,II, and III) according to the vascular morphology on CT, and their expression of CD31-, CD34-, and CD105-labeled iMVD was detected by the streptoavidin-biotin method, statistically analyzing the iMVD values of each group. The expression of CD31, CD34, and CD105 in different lung tissues was significantly different, with remarkably higher iMVD in lung cancer tissues than in adjacent normal lung tissues. In the imaging sort of types I, II, and III according to the means of vascular passage, the iMVD expression of CD31, CD34, and CD105 was significantly different between groups. These data suggest that the presence and the abnormal morphology of vessels seen within GGNs indicate the occurrence and progression of lung cancer in pathology. It offers a strong theoretical foundation for early diagnosis of carcinoma of the lungs, thus providing a more precise clinical diagnosis and prognosis of early-stage lung cancer.

Long-Cycling All-Solid-State Batteries Achieved by 2D Interface between Prelithiated Aluminum Foil Anode and Sulfide Electrolyte.

All-solid-state batteries (ASSBs) with alloy anodes are expected to achieve high energy density and safety. However, the stability of alloy anodes is largely impeded by their large volume changes during cycling and poor interfacial stability against solid-state electrolytes. Here, a mechanically prelithiation aluminum foil (MP-Al-H) is used as an anode to construct high-performance ASSBs with sulfide electrolyte. The dense Li-Al layer of the MP-Al-H foil acts as a prelithiated anode and forms a 2D interface with sulfide electrolyte, while the unlithiated Al layer acts as a tightly bound current collector and ensures the structural integrity of the electrode. Remarkably, the MP-Al-H anode exhibits superior lithium conduction kinetics and stable interfacial compatibility with Li6 PS5 Cl (LPSCl) and Li10 GeP2 S12 electrolytes. Consequently, the symmetrical cells using LPSCl electrolyte can work at a high current density of 7.5 mA cm-2 and endure for over 1500 h at 1 mA cm-2 . Notably, ≈100% capacity is retained for the MP-Al-H||LPSCl||LiCoO2 full cell with high area loadings of 18 mg cm-2 after 300 cycles. This work offers a pathway to improve the interfacial and performance issues for the application of ASSBs.

Delayed tracheal rupture following transoral endoscopic thyroidectomy vestibular approach: Case report and review of the literature.

BACKGROUND: Although the transoral endoscopic thyroidectomy vestibular approach (TOETVA) has been proven to be a safe procedure for select patients, as it is a novel approach, all associated complications require adequate attention. METHODS: We presented a 49-year old woman who underwent TOETVA developed delayed tracheal rupture 1 week after surgery. An extensive search of literature was carried out using PubMed, Embase, and Web of Science for studies reporting tracheal injury following endoscopic thyroidectomy. RESULTS: Thirteen cases of endoscopic thyroidectomy were analyzed, including eight cases of TOETVA. Tracheal injury occurred during various procedures, including accidental dissection, surgical needle puncture, Hegar dilation and trocar placement, and thermal injury by the energy device. CONCLUSIONS: Tracheal injury following TOETVA is an underreported complication that can be induced by various factors. Thermal injury to the trachea is more likely to cause a delayed rupture. Careful blunt dissection and standardized use of energy devices are suggested.

Characterization of Tremulane Sesquiterpene Synthase from the Basidiomycete Irpex lacteus.

Tremulane sesquiterpenoids are key secondary metabolites of the basidiomycete Irpex lacteus, which displays structural diversity and various bioactivities. However, tremulane sesquiterpene synthases have not been reported to date. The tremulane sesquiterpene synthase of I. lacteus was characterized by genome mining, heterologous expression, an in vitro assay, and substrate feeding. Moreover, the structures of the corresponding products were elucidated by NMR spectroscopy and X-ray diffraction analysis.

Discovery of novel DNA viruses in small mammals from Kenya.

Emergence and re-emergence of infectious diseases of wildlife origin have led pre-emptive pathogen surveillances in animals to be a public health priority. Rodents and shrews are among the most numerically abundant vertebrate taxa and are known as natural hosts of important zoonotic viruses. Many surveillance programs focused more on RNA viruses. In comparison, much less is known about DNA viruses harbored by these small mammals. To fill this knowledge gap, tissue specimens of 232 animals including 226 rodents, five shrews and one hedgehog were collected from 5 counties in Kenya and tested for the presence of DNA viruses belonging to 7 viral families by PCR. Diverse DNA sequences of adenoviruses, adeno-associated viruses, herpesviruses and polyomaviruses were detected. Phylogenetic analyses revealed that most of these viruses showed distinction from previously described viruses and formed new clusters. Furthermore, this is the first report of the discovery and full-length genome characterization of a polyomavirus in Lemniscomys species. This novel polyomavirus, named LsPyV KY187, has less than 60% amino acid sequence identity to the most related Glis glis polyomavirus 1 and Sciurus carolinensis polyomavirus 1 in both large and small T-antigen proteins and thus can be putatively allocated to a novel species within Betapolyomavirus. Our findings help us better understand the genetic diversity of DNA viruses in rodent and shrew populations in Kenya and provide new insights into the evolution of those DNA viruses in their small mammal reservoirs. It demonstrates the necessity of ongoing pathogen discovery studies targeting rodent-borne viruses in East Africa.

Genomic Characterization of Diverse Bat Coronavirus HKU10 in Hipposideros Bats.

Bats have been identified as natural reservoirs of a variety of coronaviruses. They harbor at least 19 of the 33 defined species of alpha- and betacoronaviruses. Previously, the bat coronavirus HKU10 was found in two bat species of different suborders, Rousettus leschenaultia and Hipposideros pomona, in south China. However, its geographic distribution and evolution history are not fully investigated. Here, we screened this viral species by a nested reverse transcriptase PCR in our archived samples collected over 10 years from 25 provinces of China and one province of Laos. From 8004 bat fecal samples, 26 were found to be positive for bat coronavirus HKU10 (BtCoV HKU10). New habitats of BtCoV HKU10 were found in the Yunnan, Guangxi, and Hainan Provinces of China, and Louang Namtha Province in Laos. In addition to H. pomona, BtCoV HKU10 variants were found circulating in Aselliscus stoliczkanus and Hipposideros larvatus. We sequenced full-length genomes of 17 newly discovered BtCoV HKU10 strains and compared them with previously published sequences. Our results revealed a much higher genetic diversity of BtCoV HKU10, particularly in spike genes and accessory genes. Besides the two previously reported lineages, we found six novel lineages in their new habitats, three of which were located in Yunnan province. The genotypes of these viruses are closely related to sampling locations based on polyproteins, and correlated to bat species based on spike genes. Combining phylogenetic analysis, selective pressure, and molecular-clock calculation, we demonstrated that Yunnan bats harbor a gene pool of BtCoV HKU10, with H. pomona as a natural reservoir. The cell tropism test using spike-pseudotyped lentivirus system showed that BtCoV HKU10 could enter cells from human and bat, suggesting a potential interspecies spillover. Continuous studies on these bat coronaviruses will expand our understanding of the evolution and genetic diversity of coronaviruses, and provide a prewarning of potential zoonotic diseases from bats.

CD137 agonist induces gastric cancer cell apoptosis by enhancing the functions of CD8+ T cells via NF-κB signaling.

BACKGROUND: CD137 is a target for tumor immunotherapy. However, the role of CD137 in gastric cancer (GC), especially in inducing GC cell apoptosis, has not been studied. METHODS: Foxp3+ and CD8+ T cells in GCs were investigated using immunohistochemistry (IHC). CD137 expression in GCs was detected using flow cytometry, IHC and immunofluorescence (IF). Peripheral blood mononuclear cells (PBMCs) and CD8+ T cells isolated from peripheral blood were stimulated with a CD137 agonist in vitro. CD8+ T cell proliferation and p65 expression was examined using flow cytometry. P65 nuclear translocation was analyzed using IF. IL-10, TGF-ß, IFN-γ, perforin and granzyme B were detected using real-time quantitative PCR (real-time PCR). PBMCs and primary GC cells were cocultured and stimulated with a CD137 agonist in vitro. Apoptosis of primary GC cells was detected using flow cytometry. RESULTS: Our data demonstrated that GC tumors showed characteristics of an immunosuppressive microenvironment. CD137 was predominantly expressed in CD8+ T cells in GCs and had a positive correlation with tumor cell differentiation. The CD137 agonist promoted CD8+ T cell proliferation and increased the secretion of IFN-γ, perforin and granzyme B, which induced primary GC cell apoptosis. Mechanistically, this study found that the CD137 agonist induced NF-κB nuclear translocation in CD8+ T cells. CONCLUSION: Our results demonstrated that a CD137 agonist induced primary GC cell apoptosis by enhancing CD8+ T cells via activation of NF-κB signaling.

Molecular detection of viruses in Kenyan bats and discovery of novel astroviruses, caliciviruses and rotaviruses.

This is the first country-wide surveillance of bat-borne viruses in Kenya spanning from 2012-2015 covering sites perceived to have medium to high level bat-human interaction. The objective of this surveillance study was to apply a non-invasive approach using fresh feces to detect viruses circulating within the diverse species of Kenyan bats. We screened for both DNA and RNA viruses; specifically, astroviruses (AstVs), adenoviruses (ADVs), caliciviruses (CalVs), coronaviruses (CoVs), flaviviruses, filoviruses, paramyxoviruses (PMVs), polyomaviruses (PYVs) and rotaviruses. We used family-specific primers, amplicon sequencing and further characterization by phylogenetic analysis. Except for filoviruses, eight virus families were detected with varying distributions and positive rates across the five regions (former provinces) studied. AstVs (12.83%), CoVs (3.97%), PMV (2.4%), ADV (2.26%), PYV (1.65%), CalVs (0.29%), rotavirus (0.19%) and flavivirus (0.19%). Novel CalVs were detected in Rousettus aegyptiacus and Mops condylurus while novel Rotavirus-A-related viruses were detected in Taphozous bats and R. aegyptiacus. The two Rotavirus A (RVA) strains detected were highly related to human strains with VP6 genotypes I2 and I16. Genotype I16 has previously been assigned to human RVA-strain B10 from Kenya only, which raises public health concern, particularly considering increased human-bat interaction. Additionally, 229E-like bat CoVs were detected in samples originating from Hipposideros bats roosting in sites with high human activity. Our findings confirm the presence of diverse viruses in Kenyan bats while providing extended knowledge on bat virus distribution. The detection of viruses highly related to human strains and hence of public health concern, underscores the importance of continuous surveillance.

Downregulation of SLC5A8 inhibits hepatocellular carcinoma progression through regulation of Wnt/ß-catenin signaling.

SLC5A8 has been shown to be associated with a large number of cancer progressions. However, the biological functions of SLC5A8 in hepatocellular carcinoma (HCC) remain largely unclear. Therefore, we performed this research to explore the functions of SLC5A8 in HCC progression. In this study, SLC5A8 protein and mRNA expression were examined by immunohistochemistry and quantitative real-time PCR, respectively, and we found significantly lower expression levels in HCCs than in the corresponding normal liver tissues. Low SLC5A8 expression was significantly correlated with the clinicopathological features of HCC patients. Patients with low SLC5A8 expression have a shorter overall survival time. This interpretation is confirmed by the results obtained from our in vitro experiments; functional assays indicated that overexpression of SLC5A8, by infection with a recombinant plasmid containing SLC5A8, significantly suppressed HCC cell growth, invasion, and migration and induced HCC cell apoptosis. Moreover, the expression levels of beta-catenin, cyclin D1, c-Myc, MMP-2, and FAK detected by western blotting were downregulated in SLC5A8-transfected HCC cells compared with control-transfected cells, indicating that SLC5A8 has a tumor-suppressive function that acts by interfering with Wnt/ß-catenin signaling in HCC.

The preliminary experience in simultaneous treatment of rectal cancer and synchronous liver metastases with laparoscopy.

BACKGROUND/AIMS: There is no consensus for laparoscopy first in patients with rectal cancer and synchronous liver metastases, whose metastases are confined to the liver. This study aimed to evaluate its indications for one-stage surgery in laparoscopy. MATERIALS AND METHODS: Eighteen patients with rectal cancer and synchronous liver metastases, who had undergone laparoscopic colorectal resection and simultaneous treatment for liver metastases, were retrospectively reviewed. RESULTS: Concomitant with laparoscopic colorectal resection, eight patients received liver resection simultaneously; 10 patients underwent a variety of down-staging management including local ablation, right hepatic portal vein ligation, and implantation of chemotherapy pumps into the hepatic artery. The colo-anal/rectal anastomoses were performed with a stapler or "pull-though" mode though the anus. Three patients underwent two-stage liver resection following tumor down-staging. Median survival time was 22.3 months. CONCLUSIONS: Laparoscopy approach for rectal cancer and synchronous liver metastases is feasible in selected patients. Colon pull-through anastomosis was a potential method to avoid abdominal incision and decrease the risk of anastomotic leakage. It is worth further investigation regarding its advantages over traditional modalities with a prospective randomized controlled study.

One-stage resection for Bismuth type IV hilar cholangiocarcinoma with high hilar resection and parenchyma-preserving strategies: a cohort study.

BACKGROUND: Bismuth type IV hilar cholangiocarcinoma (HC) tumors are usually considered unresectable. The strategies of high hilar resection while preserving liver parenchyma can achieve potentially one-stage curative resection for this condition. The aim of the present study was to investigate the feasibility and safety of available strategies. METHODS: Fifty-one consecutive patients with bismuth type IV HC who underwent one-stage resection were retrospectively reviewed with regard to curative resection rate, remnant liver volume, morbidity, mortality, and survival time. RESULTS: The total median survival time was 29 months. The R(0) (curative resection) rate was 57.8%. The ratio of the remnant liver volume (RLV) to the standard liver volume (SLV) ranged from 35.0 to 60.6%, with a mean of 44.5%. The in-hospital mortality and morbidity rates were 3.9 and 37.2%, respectively. In the R0 patients' survival, there was not a significant difference between bilioenteric anastomosis and hepatoenteric anastomosis (P = 0.714). CONCLUSIONS: Combined caudate lobe and high hilar resection (CCHR) is technically safe and oncologically justifiable and could be adopted with a high cure rate as a one-stage resection procedure for most patients with Bismuth type IV HC whose total bilirubin level is less than 20 mg/L and whose direct bilirubin is more than 60% of total bilirubin.