Varied immune responses of HBV-specific B cells in patients undergoing pegylated interferon-alpha treatment for chronic hepatitis B.

BACKGROUND & AIMS: The changes of HBV-specific B-cells in chronic hepatitis B (CHB) patients underwent pegylated interferon-alfa (PEG-IFNα) treatment and achieved functional cure remain unclear. We aimed to evaluate the alterations in HBV-specific B-cells during treatment and therefore explored the mechanism of functional recovery of HBsAg-specific B-cells. METHODS: We included 39 nucleos(t)ide analogues-treated CHB patients who received sequential combination therapy with PEG-IFNα and 8 treatment-naive CHB patients. HBV-specific B-cells were characterized ex vivo using fluorescent labeled HBsAg and HBcAg. The frequency, phenotype, and subsets of HBV-specific B-cells and follicular helper T cells (Tfh-cells) were detected using flow cytometry. The functionality of HBV-specific B-cells was quantified through ELISpot assays. RESULTS: During treatment, the fraction of activated memory B-cells (MBCs) among HBsAg-specific B-cells and the expression of IgG, CXCR3, and CD38 increased. Antibody-secretion capacity of HBsAg-specific B-cell was restored after treatment only in patients with a functional cure and it showed a positive correlation with serum hepatitis B surface antibody levels. The phenotype and function of HBsAg-specific B-cells differed between patients with and without functional cure. Patients with functional cure exhibited IgG+ classical MBCs and plasmablasts in HBsAg-specific B-cells. HBcAg-specific B-cells displayed both attenuated antibody secretion with reduced IgG expression and an IgM+ atypical type of MBCs after treatment, irrespective of with and without functional cure. The number of CD40L+ Tfh-cells increased after PEG-IFNα treatment and positively correlated with HBsAg-specific B-cell activation. CONCLUSIONS: After PEG-IFNα treatment, HBsAg- and HBcAg-specific B-cells exhibit various changes in antibody secretion. Their functional differences are reflected in the alterations in phenotypes and subtypes. The presence of CD40L+ Tfh-cells is associated with the active recovery of HBsAg-specific B-cells. IMPACT AND IMPLICATIONS: HBV-related complications and hepatocellular carcinoma remain the leading causes of mortality from chronic liver disease worldwide, and a cure is rarely achieved with antiviral therapies. Elucidating the immunological mechanisms underlying the functional cure of CHB patients offers a promising therapeutic strategy for viral clearance, such as therapeutic vaccine. We analyzed the alterations in HBV-specific B-cells in patients treated with PEG-IFNα and identified novel pathways for immunotherapeutic boosting of B cell immunity.

Identification and validation of a new prognostic signature based on cancer-associated fibroblast-driven genes in breast cancer.

BACKGROUND: Breast cancer (BC), a leading malignant disease, affects women all over the world. Cancer associated fibroblasts (CAFs) stimulate epithelial-mesenchymal transition, and induce chemoresistance and immunosuppression. AIM: To establish a CAFs-associated prognostic signature to improve BC patient outcome estimation. METHODS: We retrieved the transcript profile and clinical data of 1072 BC samples from The Cancer Genome Atlas (TCGA) databases, and 3661 BC samples from the The Gene Expression Omnibus. CAFs and immune cell infiltrations were quantified using CIBERSORT algorithm. CAF-associated gene identification was done by weighted gene co-expression network analysis. A CAF risk signature was established via univariate, least absolute shrinkage and selection operator regression, and multivariate Cox regression analyses. The receiver operating characteristic (ROC) and Kaplan-Meier curves were employed to evaluate the predictability of the model. Subsequently, a nomogram was developed with the risk score and patient clinical signature. Using Spearman's correlations analysis, the relationship between CAF risk score and gene set enrichment scores were examined. Patient samples were collected to validate gene expression by quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: Employing an 8-gene (IL18, MYD88, GLIPR1, TNN, BHLHE41, DNAJB5, FKBP14, and XG) signature, we attempted to estimate BC patient prognosis. Based on our analysis, high-risk patients exhibited worse outcomes than low-risk patients. Multivariate analysis revealed the risk score as an independent indicator of BC patient prognosis. ROC analysis exhibited satisfactory nomogram predictability. The area under the curve showed 0.805 at 3 years, and 0.801 at 5 years in the TCGA cohort. We also demonstrated that a reduced CAF risk score was strongly associated with enhanced chemotherapeutic outcomes. CAF risk score was significantly correlated with most hallmark gene sets. Finally, the prognostic signature were further validated by qRT-PCR. CONCLUSION: We introduced a newly-discovered CAFs-associated gene signature, which can be employed to estimate BC patient outcomes conveniently and accurately.

Artificial intelligence-aided diagnostic imaging: A state-of-the-art technique in precancerous screening.

BACKGROUND AND AIM: Chromoendoscopy with the use of indigo carmine (IC) dye is a crucial endoscopic technique to identify gastrointestinal neoplasms. However, its performance is limited by the endoscopist's skill, and no standards are available for lesion identification. Thus, we developed an artificial intelligence (AI) model to replace chromoendoscopy. METHODS: This pilot study assessed the feasibility of our novel AI model in the conversion of white-light images (WLI) into virtual IC-dyed images based on a generative adversarial network. The predictions of our AI model were evaluated against the assessments of five endoscopic experts who were blinded to the purpose of this study with a staining quality rating from 1 (unacceptable) to 4 (excellent). RESULTS: The AI model successfully transformed the WLI of polyps with different morphologies and different types of lesions in the gastrointestinal tract into virtual IC-dyed images. The quality ratings of the real IC-dyed and AI images did not significantly differ concerning surface structure (AI vs IC: 3.08 vs 3.00), lesion border (3.04 vs 2.98), and overall contrast (3.14 vs 3.02) from 10 sets of images (10 AI images and 10 real IC-dyed images). Although the score depended significantly on the evaluator, the staining methods (AI or real IC) and evaluators had no significant interaction (P > 0.05) with each other. CONCLUSION: Our results demonstrated the feasibility of employing AI model's virtual IC staining, increasing the possibility of being employed in daily practice. This novel technology may facilitate gastrointestinal lesion identification in the future.

International experts consensus guidelines on robotic liver resection in 2023.

The robotic liver resection (RLR) has been increasingly applied in recent years and its benefits shown in some aspects owing to the technical advancement of robotic surgical system, however, controversies still exist. Based on the foundation of the previous consensus statement, this new consensus document aimed to update clinical recommendations and provide guidance to improve the outcomes of RLR clinical practice. The guideline steering group and guideline expert group were formed by 29 international experts of liver surgery and evidence-based medicine (EBM). Relevant literature was reviewed and analyzed by the evidence evaluation group. According to the WHO Handbook for Guideline Development, the Guidance Principles of Development and Amendment of the Guidelines for Clinical Diagnosis and Treatment in China 2022, a total of 14 recommendations were generated. Among them were 8 recommendations formulated by the GRADE method, and the remaining 6 recommendations were formulated based on literature review and experts' opinion due to insufficient EBM results. This international experts consensus guideline offered guidance for the safe and effective clinical practice and the research direction of RLR in future.

Prevalence of Hepatitis E Virus and Its Associated Outcomes among Pregnant Women in China.

Hepatitis E virus (HEV) is a significant public health concern worldwide. Pregnant women are at high risk of severe HEV infection. Various adverse outcomes in pregnant women related to HEV infection have been well documented in low-income and middle-income countries with poor sanitation. However, previous studies have provided inconsistent conclusions regarding the effects of HEV infection on the health of pregnant women and their infants in developed countries and contemporary China. In China, previous studies on HEV in pregnant women mainly focused on anti-HEV IgM and/or anti-HEV IgG. In this study, 4244 pregnant women were retrospectively analyzed for HEV-related markers. The positive rates of HEV antigen, HEV RNA, anti-HEV IgM, and anti-HEV IgG were 0.28%, 0.54%, 0.35%, and 10.49%, respectively. Among the 467 pregnant women who tested positive for at least one HEV-related marker, 92.93% (434) were positive for anti-HEV IgG only and 0.21% (1) were positive for HEV antigen, anti-HEV IgM, and anti-HEV IgG. Although the prevalence of anti-HEV IgG significantly increased with age, the prevalence of anti-HEV IgM, HEV RNA, and HEV antigen did not differ among pregnant women of different ages. Thirty-three pregnant women were positive for at least one of anti-HEV IgM, HEV antigen, and HEV RNA, and these individuals were recently or currently infected with HEV. None of the 33 pregnant women exhibited obvious clinical symptoms. Of the 33 pregnant women, 39.39% (13) experienced adverse fetal outcomes, including preterm birth, fetal distress, and low birth weight, the incidence of which was significantly higher than in pregnant women who were not recently or currently infected with HEV. These findings suggest that maternal HEV infection may impact the health of fetuses; thus, these results may contribute to the development of appropriate public health interventions for this population.

Spatial and temporal effect and driving factors of ecosystem service trade-off in the Qingjiang River Basin, China.

Identifying the spatiotemporal differentiation characteristics of trade-offs/synergies relationships of ecosystem service in watersheds and their influencing factors is essential for ecosystem management and regulation. It is of great significance for the efficient allocation of environmental resources and the rational formulation of ecological and environmental policies. We used correlation analysis and root mean square deviation to analyze the trade-offs/synergies relationships among grain provision, net primary productivity (NPP), soil conservation, and water yield service in the Qingjiang River Basin from 2000 to 2020. Then, we analyzed the critical factors affecting the trade-offs of ecosystem services by using the geographical detector. The results showed that grain provision service in the Qingjiang River Basin presented a decreasing trend from 2000 to 2020, and that NPP, soil conservation, as well as water yield service showed an increasing trend. There was a decreasing trend in the degree of trade-offs between grain provision and soil conservation services, NPP and water yield service, and an increasing trend in the intensity of trade-offs between other services. Grain provision and NPP, soil conservation and water yield showed trade-off in the northeast and synergy in the southwest. There was a synergistic relationship between NPP with soil conservation and water yield in the central part and a trade-off relationship in the surrounding area. Soil conservation and water yield showed a high degree of synergy. Land use and normalized difference of vegetation index were the dominant factors in the intensity of trade-offs between grain provision and other ecosystem services. Precipitation, temperature, and elevation were the dominant factors in the intensity of trade-offs between water yield service and other ecosystem services. The intensity of ecosystem service trade-offs was not only affected by a single factor. In contrast, the interaction between the two services or the common factors behind the two services was the determining factor. Our results could provide a reference for developing ecological restoration planning strategies in the national land space.

Profile of clinical characteristics and serologic markers of sporadic hepatitis E in a community cohort study.

Hepatitis E virus (HEV) is a pathogen of global significance, but the value of HEV-related markers in the diagnosis of hepatitis E remains controversial. Previous studies on hepatitis E profiles have been mainly cross-sectional and conducted among inpatients in large hospitals, and hepatitis E cases have been primarily defined by limited partial markers. In this community-based study, 4,110 active hepatitis cases from a population of nearly 600,000 were followed over 48 months and serial serum samples were collected. Both HEV pathogen (HEV RNA and antigen) and anti-HEV antibody markers were used to determine HEV infection status and the relationship between hepatitis and HEV infection. In total, 98 hepatitis E patients were identified and all available isolates from 58 patients belonged to HEV genotype 4. The mean age of the patients was 58.14 years, with an overwhelming proportion of males (70.4%). Hepatitis E accounted for 22.86% of active hepatitis cases with alanine aminotransferase levels ≥15.0-fold the upper limit of normal, suggesting the need to include HEV in routine testing for these patients. Ninety-two hepatitis E patients were positive for at least 2 of HEV antigen, anti-HEV IgM, and HEV RNA markers at presentation, and 90.22% of them were positive for HEV antigen and anti-HEV IgM. HEV antigen, HEV RNA, and anti-HEV IgM positivity were observed in 89.80%, 82.65%, and 93.88% of hepatitis E patients at presentation, respectively. However, only 57.14% of anti-HEV IgM positivity occurred in hepatitis E patients. These findings will advance our understanding of hepatitis E and improve diagnosis.

Dietary taurine effect on intestinal barrier function, colonic microbiota and metabolites in weanling piglets induced by LPS.

Diarrhea in piglets is one of the most important diseases and a significant cause of death in piglets. Preliminary studies have confirmed that taurine reduces the rate and index of diarrhea in piglets induced by LPS. However, there is still a lack of relevant information on the specific target and mechanism of action of taurine. Therefore, we investigated the effects of taurine on the growth and barrier functions of the intestine, microbiota composition, and metabolite composition of piglets induced by LPS. Eighteen male weaned piglets were randomly divided into the CON group (basal diet + standard saline injection), LPS group (basal diet + LPS-intraperitoneal injection), and TAU + LPS group (basal diet + 0.3% taurine + LPS-intraperitoneal injection). The results show that taurine significantly increased the ADG and decreased the F/G (p < 0.05) compared with the group of CON. The group of TAU + LPS significantly improved colonic villous damage (p < 0.05). The expression of ZO-1, Occludin and Claudin-1 genes and proteins were markedly up-regulated (p < 0.05). Based on 16s rRNA sequencing analysis, the relative abundance of Lactobacilluscae and Firmicutes in the colon was significantly higher in the LPS + TAU group compared to the LPS group (p < 0.05). Four metabolites were significantly higher and one metabolite was significantly lower in the TAU + LPS group compared to the LPS group (p < 0.01). The above results show that LPS disrupts intestinal microorganisms and metabolites in weaned piglets and affects intestinal barrier function. Preventive addition of taurine enhances beneficial microbiota, modulates intestinal metabolites, and strengthens the intestinal mechanical barrier. Therefore, taurine can be used as a feed additive to prevent intestinal damage by regulating intestinal microorganisms and metabolites.

Prophylactic vaccines for hepatitis type E / 中华肝脏病杂志

Over the past few years, hepatitis type E has been increasingly recognized as an underestimated global disease burden. Populations with severe infection-related injuries or deaths include pregnant women, patients with underlying liver disease, and the elderly. Vaccines are the most effective means to prevent hepatitis type E virus (HEV) infection. However, the development of inactivated or attenuated vaccines is not feasible due to the lack of an efficient HEV cell culture system, so researchers have conducted in-depth research on recombinant vaccines. The capsid protein (pORF2), which the virion's open reading frame 2 encodes, contains almost exclusively the HEV neutralization site. Several candidate vaccines based on pORF2 have demonstrated potential for primate protection, with two being well tolerated and highly effective in preventing hepatitis type E in adults. Hecolin® (HEV 239 vaccine), the world's first hepatitis type E vaccine, was approved for marketing in China in 2012.

An Optimized FI-RSV Vaccine Effectively Protects Cotton Rats and BALB/c Mice without Causing Enhanced Respiratory Disease.

BACKGROUND: Despite considerable efforts toward vaccine development in past decades, no effective vaccines against respiratory syncytial virus (RSV) are available. Recently, we showed that an optimized formalin concentration can preserve prefusion protein (pre-F) on RSV-infected cells and protect mice against RSV infection without causing enhanced respiratory disease (ERD). Here, we sought to further stabilize pre-F on RSV virions by optimizing the production of FI-RSV. METHODS: Freshly produced RSV virions were treated with formalin under different concentrations to obtained an opti-FI-RSV vaccine with high pre-F level. Immunogenicity and safety of opti-FI-RSV were evaluated in Balb/c mice and cotton rats. RESULTS: Using 0.0156-0.1778% formalin, we successfully preserved pre-F on virions. This opti-FI-RSV exhibited improved immunogenicity and efficacy without causing ERD. Surprisingly, opti-FI-RSV, with a pre-F-dominant immunogen, still caused ERD after immunization with a suboptimal dose or when the neutralizing antibody titers declined. ERD was avoided by coadministering opti-FI-RSV with CpG + MPLA adjuvant, which subsequently induced a Th1-biasing immune response and, more importantly, significantly improved antibody avidity. CONCLUSIONS: Our study provides a new method to obtain a novel FI-RSV vaccine with a high pre-F level and may provide a reference for developing other inactivated vaccines. Our findings also emphasize that appropriate adjuvants are critical for nonreplicating vaccines.

Intranasal delivery of NS1-deleted influenza virus vectored COVID-19 vaccine restrains the SARS-CoV-2 inflammatory response

The emergence of SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2) variants and "anatomical escape" characteristics threaten the effectiveness of current coronavirus disease (COVID-19) vaccines. There is an urgent need to understand the immunological mechanism of broad-spectrum respiratory tract protection to guide broader vaccines development. In this study, we investigated immune responses induced by an NS1-deleted influenza virus vectored intranasal COVID-19 vaccine (dNS1-RBD) which provides broad-spectrum protection against SARS-CoV-2 variants. Intranasal delivery of dNS1-RBD induced innate immunity, trained immunity and tissue-resident memory T cells covering the upper and lower respiratory tract. It restrained the inflammatory response by suppressing early phase viral load post SARS-CoV-2 challenge and attenuating pro-inflammatory cytokine (IL-6, IL-1B, and IFN-{gamma}) levels, thereby reducing excess immune-induced tissue injury compared with the control group. By inducing local cellular immunity and trained immunity, intranasal delivery of NS1-deleted influenza virus vectored vaccine represents a broad-spectrum COVID-19 vaccine strategy to reduce disease burden.

ZLM-7 Blocks Breast Cancer Progression by Inhibiting MDM2 via Upregulation of 14-3-3 Sigma.

Breast cancer is one of the most prevalent malignancies with poor prognosis. Inhibition of angiogenesis is becoming a valid and evident therapeutic strategy to treat cancer. Recent studies uncovered the antiangiogenic activity of ZLM-7 (a combretastain A-4 derivative), but the regulatory mechanism is unclear. ZLM-7 treatment was applied in estrogen receptor-positive cell MCF-7, triple-negative breast cancer cell MDA-MB-231 and xenograft models. Transfections were conducted to overexpress or knockdown targeted genes. The gene and protein expressions were measured by qPCR and Western blotting assay, respectively. Cell proliferation and apoptosis were evaluated using the CCK8 method, clone formation assay and flow cytometry. We found that ZLM-7 upregulated 14-3-3 sigma expression but downregulated MDM2 expression in breast cancer cells. ZLM-7 delayed cell proliferation, promoted apoptosis and blocked cell-cycle progression in human breast cancer cells in vitro, while those effects were abolished by 14-3-3 sigma knockdown; overexpression of 14-3-3 sigma reproduced the actions of ZLM-7 on the cell cycle, which could be reversed by MDM2 overexpression. In xenograft models, ZLM-7 treatment significantly inhibited tumor growth while the inhibition was attenuated when 14-3-3 sigma was silenced. Collectively, ZLM-7 could inhibit MDM2 via upregulating 14-3-3 sigma expression, thereby blocking the breast cancer progression.

Epidemiological Features, Risk Factors, and Disease Burden of Respiratory Viruses among Hospitalized Children with Acute Respiratory Tract Infections in Xiamen, China.

Well-established surveillance and monitoring systems for respiratory viruses need to be improved, and epidemiological data on respiratory viruses in China are scarce. This study aimed to investigate the epidemiological characteristics of respiratory viruses among hospitalized children aged ≤2 years with acute respiratory tract infections (ARTIs) in Xiamen, China, from October 2014 to September 2017. The clinical records of 7,248 children hospitalized for ARTIs were retrospectively analyzed. Respiratory syncytial virus (RSV) (22.3%) was the most common virus among hospitalized children aged ≤2 years, followed by parainfluenza (5.0%), adenovirus (3.5%), and influenza (1.7%). RSV-infected children had a higher disease burden, including a higher intensive care unit (ICU) admission rate (12.7%) and higher hospital charges ($635.36). Particularly, infants aged <6 months had the highest risk of RSV infection (odds ratio = 2.4; 95% CI, 1.9-2.9) and a higher ICU admission rate (12.1% vs. 4.5%, 4.6%) and hospital cost ($923.3 vs. $785.5, $811.7) than the other age groups. Therefore, infants aged 0-6 months, particularly premature infants and children with congenital diseases, should receive more attention. There is an urgent need to develop effective immunization strategies to protect these infants during the first 6 months of life and in the RSV season.

Molecular Evolution of Attachment Glycoprotein (G) and Fusion Protein (F) Genes of Respiratory Syncytial Virus ON1 and BA9 Strains in Xiamen, China.

Monitoring viral transmission and analyzing the genetic diversity of a virus are imperative to better understand its evolutionary history and the mechanism driving its evolution and spread. Especially, effective monitoring of key antigenic mutations and immune escape variants caused by these mutations has great scientific importance. Thus, to further understand the molecular evolutionary dynamics of respiratory syncytial virus (RSV) circulating in China, we analyzed nasopharyngeal swab specimens derived from hospitalized children ≤5 years old with acute respiratory tract infections (ARIs) in Xiamen during 2016 to 2019. We found that infants under 6 months of age (52.0%) were the main population with RSV infection. The prevalent pattern "BBAA" of RSV was observed during the epidemic seasons. RSV ON1 and BA9 genotypes were the dominant circulating strains in Xiamen. Interestingly, we observed four Xiamen-specific amino acid substitution combinations in the G protein and several amino acid mutations primarily occurring at antigenic sites Ø and V in the F protein. Our analyses suggest that introduction of new viruses and local evolution are shaping the diversification of RSV strains in Xiamen. This study provides new insights on the evolution and spread of the ON1 and BA9 genotypes at local and global scales. IMPORTANCE Monitoring the amino acid diversity of the RSV G and F genes helps us to find the novel genotypes, key antigenic mutations affecting antigenicity, or neutralizing antibody-resistant variants produced by natural evolution. In this study, we analyzed the molecular evolution of G and F genes from RSV strains circulating in Xiamen, China. These data provide new insights on local and global transmission and could inform the development of control measures for RSV infections.

Highly Conjugated Graphitic Carbon Nitride Nanofoam for Photocatalytic Hydrogen Evolution.

As a metal-free photocatalyst, graphitic carbon nitride (g-CN) shows great potential for photocatalytic water splitting, although its performance is significantly limited by structural defects due to incomplete polymerization. In the present work, we successfully synthesize highly conjugated g-CN nanofoam through an iodide substitution technique. The product possesses a high polymerization degree, low defect density, and large specific surface area; as a result, it achieves a hydrogen evolution rate of 9.06 mmol h-1 g-1 under visible light irradiation, with an apparent quantum efficiency (AQE) of 18.9% at 420 nm. Experimental analysis and theoretical calculations demonstrate that the recombination of photogenerated carriers at C-NHx defects was effectively depressed in the nanofoam, giving rise to the high photocatalytic activity.

International Expert Consensus on Precision Anatomy for minimally invasive distal pancreatectomy: PAM-HBP Surgery Project.

BACKGROUND: Surgical views with high resolution and magnification have enabled us to recognize the precise anatomical structures that can be used as landmarks during minimally invasive distal pancreatectomy (MIDP). This study aimed to validate the usefulness of anatomy-based approaches for MIDP before and during the Expert Consensus Meeting: Precision Anatomy for Minimally Invasive HBP Surgery (February 24, 2021). METHODS: Twenty-five international MIDP experts developed clinical questions regarding surgical anatomy and approaches for MIDP. Studies identified via a comprehensive literature search were classified using Scottish Intercollegiate Guidelines Network methodology. Online Delphi voting was conducted after experts had drafted the recommendations, with the goal of obtaining >75% consensus. Experts discussed the revised recommendations in front of the validation committee and an international audience of 384 attendees. Finalized recommendations were made after a second round of online Delphi voting. RESULTS: Four clinical questions were addressed, resulting in 10 recommendations. All recommendations reached at least a 75% consensus among experts. CONCLUSIONS: The expert consensus on precision anatomy for MIDP has been presented as a set of recommendations based on available evidence and expert opinions. These recommendations should guide experts and trainees in performing safe MIDP and foster its appropriate dissemination worldwide.

Comparison of robotic and open pancreaticoduodenectomy for primary nonampullary duodenal adenocarcinoma: a retrospective cohort study.

PURPOSE: Robotic surgery has been increasingly applied in pancreatic surgery and showed many advantages over conventional open surgery. The robotic pancreaticoduodenectomy (RPD) is a surgical option for primary nonampullary duodenal adenocarcinoma (PNDA). However, whether RPD is superior to open pancreaticoduodenectomy (OPD) for PNDA has not been reported. The comparative study was designed to analyze the short- and long-term outcomes of RPD versus OPD on patients with PNDA. METHODS: Demographics, perioperative, and survival outcomes among patients who underwent RPD (n = 49) versus OPD (n = 43) for PNDAs between January 2013 and March 2018 were collected and analyzed RESULTS: Demographic characteristics were comparable between the RPD group and the OPD group. The RPD group demonstrated a decreased estimated blood loss (100 vs. 200 ml, p < 0.001), time to oral intake (4.0 vs. 4.0 days, p = 0.04), and postoperative hospital stay (12.9 vs. 15.0 days, p = 0.01) compared with the OPD group. However, no differences were observed between the two groups in terms of operative time and the rates of major complications, grade B and C POPF, PPH, grade B and C DGE, biliary fistular, reoperation, and 90-day readmission. No patient died within 90 days. There were no significant differences in tumor size, differentiation, TNM stage, number of harvested lymph nodes, and the rates of nerve invasion, lymph node invasion, R0 resection, and the median overall survival between the two groups (p > 0.05) CONCLUSIONS: RPD is a safe, feasible, and effective treatment for PNDA compared with OPD and can be used as an alternative for surgeons in the treatment of PNDA. Further multicenter randomized controlled trials are needed to evaluate the effectiveness of RPD in patients with PNDA.

International expert consensus on precision anatomy for minimally invasive pancreatoduodenectomy: PAM-HBP surgery project.

BACKGROUND: The anatomical structure around the pancreatic head is very complex and it is important to understand its precise anatomy and corresponding anatomical approach to safely perform minimally invasive pancreatoduodenectomy (MIPD). This consensus statement aimed to develop recommendations for elucidating the anatomy and surgical approaches to MIPD. METHODS: Studies identified via a comprehensive literature search were classified using the Scottish Intercollegiate Guidelines Network method. Delphi voting was conducted after experts had drafted recommendations, with a goal of obtaining >75% consensus. Experts discussed the revised recommendations with the validation committee and an international audience of 384 attendees. Finalized recommendations were made after a second round of online Delphi voting. RESULTS: Three clinical questions were addressed, providing six recommendations. All recommendations reached at least a consensus of 75%. Preoperatively evaluating the presence of anatomical variations and superior mesenteric artery (SMA) and superior mesenteric vein (SMV) branching patterns was recommended. Moreover, it was recommended to fully understand the anatomical approach to SMA and intraoperatively confirm the SMA course based on each anatomical landmark before initiating dissection. CONCLUSIONS: MIPD experts suggest that surgical trainees perform resection based on precise anatomical landmarks for safe and reliable MIPD.

The prognostic value of end-of-treatment FDG-PET/CT in diffuse large B cell lymphoma: comparison of visual Deauville criteria and a lesion-to-liver SUVmax ratio-based evaluation system.

PURPOSE: The aim of this study was to determine a better criterion for end-of-treatment PET (EoT-PET) assessment and prognostic evaluation of patients with diffuse large B cell lymphoma (DLBCL). METHOD: EoT-PET scans were assessed using the visual Deauville 5-point scale (5PS) and LLR, the maximum standard uptake value ratio between the lesion and the liver. The cutoff value of LLR was obtained by receiver operator characteristic curve analysis. Patient outcomes were compared using Kaplan-Meier survival analysis. Prognostic indexes of different criteria were compared. Multivariate Cox regression analysis was performed to evaluate the prognostic factors. RESULTS: Four hundred forty-nine newly diagnosed DLBCL patients who received rituximab-based immunochemotherapy were included, and the median follow-up duration was 41.4 months. Patients with Deauville score (DS) 4 displayed significantly longer PFS and OS compared with patients with DS 5 (both p < 0.001), and they had significantly shorter PFS (p < 0.01) but similar OS (p = 0.057) compared with patients with DS 1-3. The differences in PFS and OS between groups were all significant whether positive EoT-PET was defined as DS 4-5 or DS 5 (all p < 0.001). The optimal cutoff of LLR was 1.83, and both PFS and OS were significantly different between EoT-PET-positive and EoT-PET-negative patients as defined by the cutoff (both p < 0.001). LLR-based criterion displayed higher specificity, positive predictive value, and accuracy than 5PS-based criterion in the prediction of disease progression and death events. In the multivariate analysis, positive EoT-PET (as defined by LLR) was related to unfavorable PFS and OS (both p < 0.001). Additional treatment was not correlated with outcomes of EoT-PET-negative patients either defined by LLR or 5PS or EoT-PET-positive patients classified by 5PS, but it was the only beneficial factor for OS (p < 0.05) in EoT-PET-positive patients with LLR ≥ 1.83. CONCLUSION: The optimal cutoff of LLR may be superior to Deauville criteria in identifying low-risk DLBCL patients with negative EoT-PET after the first-line immunochemotherapy and sparing them the cost and toxicity of additional treatment.

Prognostic Factors and a Nomogram Predicting Survival in Patients with Breast Ductal Carcinoma in situ with Microinvasion: A Population-Based Study.

PURPOSE: Ductal carcinoma in situ with microinvasion (DCISM) can be challenging to balance the risks of overtreatment versus undertreatment. We aim to identify prognostic factors in patients with DCISM and construct a nomogram to predict breast cancer-specific survival (BCSS). MATERIALS AND METHODS: A retrospective cohort study of women diagnosed with DCISM from 1988 to 2015 who were identified in the Surveillance, Epidemiology and End Results database. Clinical variables and tumor characteristics were evaluated, and Cox proportional-hazards regression was performed. A nomogram was constructed from the multivariate logistic regression to combine all the prognostic factors to predict the prognosis of DCISM patients at 5 years, 10 years, and 15 years. RESULTS: We identified 5438 total eligible breast cancer patients with a median and max survival time of 78 and 227 months, respectively. Here, patients with poorer survival outcomes were those diagnosed between 1988 and 2001, African-American race, under 40 years of age, higher tumor N stage, progesterone receptor-negative tumor, and received no surgery. The nomogram was constructed by the seven variables and passed the calibration and validation steps. The area under the receiver operating characteristic (ROC) curve (AUC) of both the training set and the validating set (5-year AUC: 0.77 and 0.88, 10-year AUC: 0.75 and 0.73, 15-year AUC: 0.72 and 0.65). Receiving chemotherapy was associated with a better BCSS (hazard ratio, HR=0.45, 95% confidence interval, 95% CI = 0.23-0.89), especially in patients with estrogen receptor (ER) negative, progesterone receptor (PR) negative (HR = 0.35, 95% CI = 0.13-0.97) and ER+PR-/ER-PR+ DCISM (HR = 0.07, 95% CI = 0.01-0.59). CONCLUSION: Our current study is the first to construct nomograms of patients with DCISM which could help physicians identify breast cancer patients that more likely to benefit from more intensive treatment and follow-up. Chemotherapy might benefit patients with ER-PR- and ER+PR-/ER-PR+ DCISM.