The application and progress of tissue engineering and biomaterial scaffolds for total auricular reconstruction in microtia.

Microtia is a congenital deformity of the ear with an incidence of about 0.8-4.2 per 10,000 births. Total auricular reconstruction is the preferred treatment of microtia at present, and one of the core technologies is the preparation of cartilage scaffolds. Autologous costal cartilage is recognized as the best material source for constructing scaffold platforms. However, costal cartilage harvest can lead to donor-site injuries such as pneumothorax, postoperative pain, chest wall scar and deformity. Therefore, with the need of alternative to autologous cartilage, in vitro and in vivo studies of biomaterial scaffolds and cartilage tissue engineering have gradually become novel research hot points in auricular reconstruction research. Tissue-engineered cartilage possesses obvious advantages including non-rejection, minimally invasive or non-invasive, the potential of large-scale production to ensure sufficient donors and controllable morphology. Exploration and advancements of tissue-engineered cartilaginous framework are also emerging in aspects including three-dimensional biomaterial scaffolds, acquisition of seed cells and chondrocytes, 3D printing techniques, inducing factors for chondrogenesis and so on, which has greatly promoted the research process of biomaterial substitute. This review discussed the development, current application and research progress of cartilage tissue engineering in auricular reconstruction, particularly the usage and creation of biomaterial scaffolds. The development and selection of various types of seed cells and inducing factors to stimulate chondrogenic differentiation in auricular cartilage were also highlighted. There are still confronted challenges before the clinical application becomes widely available for patients, and its long-term effect remains to be evaluated. We hope to provide guidance for future research directions of biomaterials as an alternative to autologous cartilage in ear reconstruction, and finally benefit the transformation and clinical application of cartilage tissue engineering and biomaterials in microtia treatment.

The application and progress of stem cells in auricular cartilage regeneration: a systematic review.

Background: The treatment of microtia or acquired ear deformities by surgery is a significant challenge for plastic and ENT surgeons; one of the most difficult points is constructing the scaffold for auricular reconstruction. As a type of cell with multiple differentiation potentials, stem cells play an essential role in the construction of cartilage scaffolds, and therefore have received widespread attention in ear reconstructive research. Methods: A literature search was conducted for peer-reviewed articles between 2005 and 2023 with the following keywords: stem cells; auricular cartilage; ear cartilage; conchal cartilage; auricular reconstruction, regeneration, and reparation of chondrocytes; tissue engineering in the following databases: PubMed, MEDLINE, Cochrane, and Ovid. Results: Thirty-three research articles were finally selected and their main characteristics were summarized. Adipose-derived stem cells (ADSCs), bone marrow mesenchymal stem cells (BMMSCs), perichondrial stem/progenitor cells (PPCs), and cartilage stem/progenitor cells (CSPCs) were mainly used in chondrocyte regeneration. Injecting the stem cells into the cartilage niche directly, co-culturing the stem cells with the auricular cartilage cells, and inducing the cells in the chondrogenic medium in vitro were the main methods that have been demonstrated in the studies. The chondrogenic ability of these cells was observed in vitro, and they also maintained good elasticity and morphology after implantation in vivo for a period of time. Conclusion: ADSC, BMMSC, PPC, and CSPC were the main stem cells that have been researched in craniofacial cartilage reconstruction, the regenerative cartilage performed highly similar to normal cartilage, and the test of AGA and type II collagen content also proved the cartilage property of the neo-cartilage. However, stem cell reconstruction of the auricle is still in the initial stage of animal experiments, transplantation with such scaffolds in large animals is still lacking, and there is still a long way to go.

Bioengineered MSC-derived exosomes in skin wound repair and regeneration.

Refractory skin defects such as pressure ulcers, diabetic ulcers, and vascular ulcers represent a challenge for clinicians and researchers in many aspects. The treatment strategies for wound healing have high cost and limited efficacy. To ease the financial and psychological burden on patients, a more effective therapeutic approach is needed to address the chronic wound. MSC-derived exosomes (MSC-exosomes), the main bioactive extracellular vesicles of the paracrine effect of MSCs, have been proposed as a new potential cell-free approach for wound healing and skin regeneration. The benefits of MSC-exosomes include their ability to promote angiogenesis and cell proliferation, increase collagen production, regulate inflammation, and finally improve tissue regenerative capacity. However, poor targeting and easy removability of MSC-exosomes from the wound are major obstacles to their use in clinical therapy. Thus, the concept of bioengineering technology has been introduced to modify exosomes, enabling higher concentrations and construction of particles of greater stability with specific therapeutic capability. The use of biomaterials to load MSC-exosomes may be a promising strategy to concentrate dose, create the desired therapeutic efficacy, and maintain a sustained release effect. The beneficial role of MSC-exosomes in wound healing is been widely accepted; however, the potential of bioengineering-modified MSC-exosomes remains unclear. In this review, we attempt to summarize the therapeutic applications of modified MSC-exosomes in wound healing and skin regeneration. The challenges and prospects of bioengineered MSC-exosomes are also discussed.

Grading Complications in Pelvic Exenteration: Limitations of Current Classification Systems.

OBJECTIVE: To comprehensively report complications associated with pelvic exenteration and to determine the strength of associations between 3 different grading methodologies and length of stay, quality of life, and physical outcomes. BACKGROUND: It is generally accepted that pelvic exenteration is associated with high rates of surgical morbidity. However, methods of reporting in the literature are inconsistent, making it difficult to compare surgical outcomes across studies to determine the impact of surgery on patients. DESIGN: A retrospective study. SETTINGS: This study was conducted at Royal Prince Alfred Hospital, Sydney, Australia. PATIENTS: It included patients who underwent pelvic exenteration between December 2016 and August 2019. MAIN OUTCOME MEASURES: Complications were classified according to the Clavien-Dindo classification, Comprehensive Complication Index, and number of postoperative complications. Correlations between length of stay, physical component score, 6-minute walk test, and sit-to-stand test, and complications as graded using the Clavien-Dindo classification, Comprehensive Complication Index, and the number of complications were explored using Pearson's or point biserial correlation tests. RESULTS: In this study, 198 patients were included. The Clavien-Dindo classification was moderately positively correlated with length of stay ( r = 0.519; p < 0.0001), whereas Comprehensive Complication Index ( r = 0.744; p < 0.0001) and the number of complications ( r = 0.751; p < 0.0001) showed a strong correlation with length of stay. All these methodologies were moderately inversely correlated with a predischarge 6-minute walk test (Clavien-Dindo classification: r = -0.359, p = 0.008; Comprehensive Complication Index: r = -0.388, p = 0.007; number of complications: r = -0.467, p < 0.0001). LIMITATIONS: This single-center retrospective study involves a small sample size. Classification of grade I and II complications in this cohort of patients who tend to have complex postoperative recovery was challenging and therefore incomplete. The incomplete data may have affected the correlations. CONCLUSIONS: Comprehensive Complication Index and the number of postoperative complications were more strongly correlated with length of stay than the Clavien-Dindo classification in patients undergoing pelvic exenteration. Comprehensive Complication Index may be a better grading system to classify postoperative complications following pelvic exenteration. See Video Abstract at http://links.lww.com/DCR/B906 . CLASIFICACIN DE LAS COMPLICACIONES EN LA EXENTERACIN PLVICA LIMITACIONES DE LOS SISTEMAS DE CLASIFICACIN ACTUALES: OBJETIVO:Este estudio tuvo como objetivo informar de manera integral las complicaciones asociadas con la exanteración pélvica y determinar la rlacion de las asociaciones entre tres metodologías de clasificación diferentes y la duración de la estadía, la calidad de vida y los resultados físicos.ANTECEDENTES:En general, se acepta que la exanteración pélvica se asocia con altas tasas de morbilidad quirúrgica. Sin embargo, los métodos de notificación en la literatura son inconsistentes, lo que dificulta la comparación de los resultados quirúrgicos entre estudios para determinar el impacto de la cirugía en los pacientes.DISEÑO:Este fue un estudio retrospectivo.AJUSTES:Este estudio se realizó en el Royal Prince Alfred Hospital, Sydney. Australia.PACIENTES:Se incluyeron pacientes a las que se les realizó exenteración pélvica entre diciembre de 2016 y agosto de 2019.PRINCIPALES MEDIDAS DE RESULTADO:Las complicaciones se clasificaron de acuerdo con la Clasificación de Clavien-Dindo, el Índice Integral de Complicaciones y el número de complicaciones posoperatorias. Correlaciones entre la duración de la estadía, la puntuación del componente físico, la prueba de caminata de 6 minutos y la prueba de sentarse y levantarse; y las complicaciones según la clasificación de Clavien-Dindo, el CCI y el número de complicaciones se exploraron mediante las pruebas de correlación biserial de Pearson o Point.RESULTADOS:Un total de 198 pacientes fueron incluidos en este estudio. La clasificación de Clavien-Dindo se correlacionó moderadamente positivamente con la duración de la estancia ( r = 0,519, p < 0,0001), mientras que el índice de complicaciones integrales ( r = 0,744, p < 0,0001) y el número de complicaciones ( r = 0,751, p < 0,0001) mostraron una fuerte correlación con la duración de la estancia. Todas estas metodologías se correlacionaron moderadamente inversamente con la prueba de caminata de 6 minutos antes del alta (Clasificación de Clavien-Dindo: r = -0,359, p = 0,008; Índice de Complicaciones Integrales: r = -0,388, p = 0,007; número de complicaciones: r = -0,467, p < 0,0001).LIMITACIONES:Un estudio retrospectivo de un solo centro incluye un tamaño de muestra pequeño. La clasificación de las complicaciones de grado I y II en esta cohorte de pacientes que tienden a tener una recuperación postoperatoria compleja fue un desafío y, por lo tanto, incompleta. Los datos incompletos pueden haber afectado las correlaciones.CONCLUSIONES:El Índice Integral de Complicaciones y el número de complicaciones postoperatorias se correlacionaron más con la duración de la estancia que la Clasificación de Clavien-Dindo en pacientes con exenteración pélvica. El Índice Integral de Complicaciones puede ser un mejor sistema de clasificación para clasificar las complicaciones posoperatorias después de la exenteración pélvica. Consulte Video Resumen en http://links.lww.com/DCR/B906 . (Traducción-Dr. Yolanda Colorado ).

Hand-assisted versus straight laparoscopy for colorectal surgery - a systematic review and meta-analysis.

PURPOSE: Hand-assisted laparoscopic surgery (HALS) is an alternative to straight laparoscopy (LAP) in colorectal surgery. Many studies have compared the two in terms of efficacy, complications, and outcomes. This meta-analysis aims to uncover if there are any significant differences in conversion rates, operative times, body mass index (BMI), incision lengths, intraoperative and postoperative complications, and length of stay. METHODS: Comprehensive searches were performed on databases from their respective inceptions to 16 December 2021, with a manual search performed through Scopus. Randomized controlled trials (RCTs), cohort studies, and case series involving more than 10 patients were included. RESULTS: A total of 47 studies were found fitting the inclusion criteria, with 5 RCTs, 41 cohort studies, and 1 case series. Hand-assisted laparoscopic surgery was associated with lower conversion rates (odds ratio [OR] 0.41, 95%CI 0.28-0.60, p < 0.00001), shorter operative times (Mean Difference [MD] - 8.32 min, 95%CI - 14.05- - 2.59, p = 0.004), and higher BMI (MD 0.79, 95%CI 0.46-1.13, p < 0.00001), but it was also associated with longer incision lengths (MD 2.19 cm, 95%CI 1.66-2.73 cm, p < 0.00001), and higher postoperative complication rates (OR 1.15, 95%CI 1.06-1.24, p = 0.0004). Length of stay was not different in HALS as compared to Lap (MD 0.16 days, 95%CI - 0.06-0.38 days, p = 0.16, and intraoperative complications were the same between both techniques. CONCLUSIONS: Hand-assisted laparoscopy is a suitable alternative to straight laparoscopy with benefits and risks. While there are many cohort studies comparing HALS and LAP, more RCTs would be needed for a better quality of evidence.

Differences in Surgical Outcomes and Quality-of-Life Outcomes in Pelvic Exenteration Between Locally Advanced Versus Locally Recurrent Rectal Cancers.

BACKGROUND: Although pelvic exenteration remains the only curative option for locally advanced rectal cancer and locally recurrent rectal cancer, only limited evidence is available on the differences in surgical and quality-of-life outcomes between the two. OBJECTIVE: This study aimed to compare surgical outcomes and identify any differences or predictors of quality of life of patients with locally advanced rectal cancer and locally recurrent rectal cancer undergoing pelvic exenteration. DESIGN: This was a cohort study. SETTING: This study was conducted at Royal Prince Alfred Hospital, Sydney, Australia. PATIENTS: This study included patients with locally advanced rectal cancer and locally recurrent rectal cancer who underwent pelvic exenteration between July 2008 and March 2019. MAIN OUTCOME MEASURES: The main outcome measures included Short Form 36 version 2 and Functional Assessment of Cancer Therapy-Colorectal score. RESULTS: A total of 271 patients were included in this study. Locally advanced rectal cancer patients had higher rates of R0 resection ( p = 0.003), neoadjuvant chemoradiotherapy ( p < 0.001), and had greater median overall survival (75.1 vs. 45.8 months), although the latter was clinically but not statistically significant. There was a higher blood loss ( p < 0.001), longer length of stay ( p = 0.039), and longer operative time ( p = 0.002) in the locally recurrent rectal cancer group. This group also had a higher mean baseline physical component summary score and Functional Assessment of Cancer Therapy-Colorectal score; however, there were no significant differences in complications or quality-of-life outcomes between with the two groups at any time points postoperatively up to 12 months. LIMITATION: The study was from a specialized experienced center, which could limit its generalizability. CONCLUSIONS: Patients with locally recurrent rectal cancer tend to require a more extensive surgery with a longer operative time and more blood loss and longer recovery from surgery, but despite this, their quality of life is comparable to those with locally advanced rectal cancer. See Video Abstract at http://links.lww.com/DCR/B1000 . DIFERENCIAS EN LOS RESULTADOS QUIRRGICOS Y LOS RESULTADOS DE LA CALIDAD DE VIDA EN LA EXENTERACIN PLVICA ENTRE EL CNCER DE RECTO LOCALMENTE AVANZADO Y EL CNCER DE RECTO LOCALMENTE RECIDIVANTE: ANTECEDENTES:Aunque la exenteración pélvica sigue siendo la única opción curativa para el cáncer de recto localmente avanzado y el cáncer de recto localmente recurrente, solo hay evidencia limitada disponible sobre las diferencias en los resultados quirúrgicos y de calidad de vida entre los dos.OBJETIVO:Este estudio tuvo como objetivo comparar los resultados quirúrgicos e identificar cualquier diferencia o predictor de la calidad de vida de los pacientes con cáncer de recto localmente avanzado y cáncer de recto localmente recurrente sometidos a exenteración pélvica.DISEÑO:Este fue un estudio de cohorte.AJUSTE:Este estudio se realizó en el Royal Prince Alfred Hospital, Sydney, Australia.PACIENTES:Este estudio incluyó pacientes con cáncer de recto localmente avanzado y cáncer de recto localmente recurrente que se sometieron a exenteración pélvica entre julio de 2008 y marzo de 2019.PRINCIPALES MEDIDAS DE RESULTADO:Las principales medidas de resultado incluyeron el formulario corto 36 versión 2 y la puntuación de la evaluación funcional de la terapia del cáncer colorrectal.RESULTADOS:Un total de 271 pacientes fueron incluidos en este estudio. Los pacientes con cáncer de recto localmente avanzado tuvieron tasas más altas de resección R0 ( p = 0,003), quimiorradioterapia neoadyuvante ( p < 0,001) y una mediana de supervivencia general más alta (75,1 frente a 45,8 meses),a pesar de que esta última fue clínica pero no estadísticamente significativa. Hubo una mayor pérdida de sangre ( p < 0,001), una estancia más prolongada ( p = 0,039) y un tiempo operatorio más prolongado ( p = 0,002) en el grupo de cáncer de recto localmente recurrente. También tenían una puntuación de componente físico inicial media más alta y una puntuación de Evaluación funcional de la terapia del cáncer colorrectal; sin embargo, no hubo diferencias significativas en las complicaciones o los resultados de la calidad de vida entre los dos grupos en ningún momento después de la operación hasta los 12 meses.LIMITACIÓN:El estudio fue de un centro especializado con experiencia, lo que podría limitar su generalización.CONCLUSIONES:Los pacientes con cáncer de recto localmente recurrente tienden a requerir una cirugía más extensa con un tiempo operatorio más largo y más pérdida de sangre y una recuperación más prolongada de la cirugía, pero a pesar de esto, su calidad de vida es comparable a aquellos con cáncer de recto localmente avanzado. Consulte Video Resumen en http://links.lww.com/DCR/B1000 . (Traducción-Dr. Yolanda Colorado ).

Management of appendicitis in a De Garengeot hernia: Lockwood approach.

A De Garengeot hernia is a femoral hernia containing the vermiform appendix. This extremely rare hernia is associated with appendicitis and the risk of perforation and abscess formation. Given limited data, it poses both diagnostic and management difficulties. While management is generally surgical, questions remain about the best operative approach, indications for appendicectomy and optimum hernia repair technique. We describe a case of acute appendicitis within a De Garengeot hernia that was managed with an open appendicectomy via a Lockwood incision. This case helps to illustrate the management considerations present for this rare clinical pathology and describes a method to effectively identify the hernia and resect the appendix.

Histopathological Images and Multi-Omics Integration Predict Molecular Characteristics and Survival in Lung Adenocarcinoma.

Histopathological images and omics profiles play important roles in prognosis of cancer patients. Here, we extracted quantitative features from histopathological images to predict molecular characteristics and prognosis, and integrated image features with mutations, transcriptomics, and proteomics data for prognosis prediction in lung adenocarcinoma (LUAD). Patients obtained from The Cancer Genome Atlas (TCGA) were divided into training set (n = 235) and test set (n = 235). We developed machine learning models in training set and estimated their predictive performance in test set. In test set, the machine learning models could predict genetic aberrations: ALK (AUC = 0.879), BRAF (AUC = 0.847), EGFR (AUC = 0.855), ROS1 (AUC = 0.848), and transcriptional subtypes: proximal-inflammatory (AUC = 0.897), proximal-proliferative (AUC = 0.861), and terminal respiratory unit (AUC = 0.894) from histopathological images. Moreover, we obtained tissue microarrays from 316 LUAD patients, including four external validation sets. The prognostic model using image features was predictive of overall survival in test and four validation sets, with 5-year AUCs from 0.717 to 0.825. High-risk and low-risk groups stratified by the model showed different survival in test set (HR = 4.94, p < 0.0001) and three validation sets (HR = 1.64-2.20, p < 0.05). The combination of image features and single omics had greater prognostic power in test set, such as histopathology + transcriptomics model (5-year AUC = 0.840; HR = 7.34, p < 0.0001). Finally, the model integrating image features with multi-omics achieved the best performance (5-year AUC = 0.908; HR = 19.98, p < 0.0001). Our results indicated that the machine learning models based on histopathological image features could predict genetic aberrations, transcriptional subtypes, and survival outcomes of LUAD patients. The integration of histopathological images and multi-omics may provide better survival prediction for LUAD.

Integrative radiogenomics analysis for predicting molecular features and survival in clear cell renal cell carcinoma.

OBJECTIVES: To assess the feasibility of predicting molecular characteristics by computed tomography (CT) radiomics features, and predicting overall survival (OS) using combination of omics data in clear cell renal cell carcinoma (ccRCC). METHODS: Genetic data of 207 ccRCC patients was retrieved from The Cancer Genome Atlas (TCGA) and matched contrast-enhanced CT images were obtained from The Cancer Imaging Archive (TCIA). Another cohort of 175 ccRCC patients from West China Hospital was used as external validation. We first applied radiomics features and machine learning algorithms to predict genetic mutations and mRNA-based molecular subtypes. Next, we established predictive models for OS based on single omics, combined omics (radiomics+genomics, radiomics+transcriptomics, radiomics+proteomics) and all features (multi-omics). RESULTS: Using radiomics features, random forest algorithm showed good capacity to identify the mutations VHL (AUC=0.971), BAP1 (AUC=0.955), PBRM1 (AUC=0.972), SETD2 (AUC=0.949), and molecular subtypes m1 (AUC=0.973), m2 (AUC=0.968), m3 (AUC=0.961), m4 (AUC=0.953). The TCGA cohort was divided into training (n=104) and validation (n=103) sets. The radiomics model had promising prognostic value for OS in validation set (5-year AUC=0.775) and external validation set (5-year AUC=0.755). In the validation set, the radiomics+omics models enhanced predictive accuracy than single-omics models, and the multi-omics model made further improvement (5-year AUC=0.846). High-risk group of validation set predicted by multi-omics model showed significantly poorer OS (HR=6.20, 95%CI: 3.19-8.44, p<0.0001). CONCLUSIONS: CT radiomics might be a feasible approach to predict genetic mutations, molecular subtypes and OS in ccRCC patients. Integrative analysis of radiogenomics may improve the survival prediction of ccRCC patients.

Exploration of an Integrative Prognostic Model of Radiogenomics Features With Underlying Gene Expression Patterns in Clear Cell Renal Cell Carcinoma.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is one of the most common malignancies in urinary system, and radiomics has been adopted in tumor staging and prognostic evaluation in renal carcinomas. This study aimed to integrate image features of contrast-enhanced CT and underlying genomics features to predict the overall survival (OS) of ccRCC patients. METHOD: We extracted 107 radiomics features out of 205 patients with available CT images obtained from TCIA database and corresponding clinical and genetic information from TCGA database. LASSO-COX and SVM-RFE were employed independently as machine-learning algorithms to select prognosis-related imaging features (PRIF). Afterwards, we identified prognosis-related gene signature through WGCNA. The random forest (RF) algorithm was then applied to integrate PRIF and the genes into a combined imaging-genomics prognostic factors (IGPF) model. Furthermore, we constructed a nomogram incorporating IGPF and clinical predictors as the integrative prognostic model for ccRCC patients. RESULTS: A total of four PRIF and four genes were identified as IGPF and were represented by corresponding risk score in RF model. The integrative IGPF model presented a better prediction performance than the PRIF model alone (average AUCs for 1-, 3-, and 5-year were 0.814 vs. 0.837, 0.74 vs. 0.806, and 0.689 vs. 0.751 in test set). Clinical characteristics including gender, TNM stage and IGPF were independent risk factors. The nomogram integrating clinical predictors and IGPF provided the best net benefit among the three models. CONCLUSION: In this study we established an integrative prognosis-related nomogram model incorporating imaging-genomic features and clinical indicators. The results indicated that IGPF may contribute to a comprehensive prognosis assessment for ccRCC patients.

Safety and Efficacy of Pancreaticoduodenectomy in Octogenarians.

Backgrounds: Pancreaticoduodenectomy (PD) remains the only hope of a cure in selected patients with pancreatic adenocarcinoma (PAC). With an aging population, there will be an increasing number of very elderly patients being diagnosed with PAC of whom a selected proportion would be suitable for PD. However, the literature on outcomes of elderly patients after PD remains ambiguous. Therefore, the aim of this study was to examine the safety and efficacy of PD in octogenarians with PAC. Methods: A retrospective analysis of 304 patients with PAC undergoing PD. Patients were divided into two age groups using age of 80 years old as the cut-off. Results: Overall mortality and major morbidity rates were 0.5 and 18.5%, respectively. The octogenarian group had a higher rate of mortality (6.3%, n = 1, p < 0.001), a higher rate of major morbidity (37.5%, n = 6, p = 0.042) and a longer hospital stay (p = 0.035). However, median survival of octogenarians was 15.6 months. Multivariate analysis showed age was not identified as a prognostic factor for major morbidity and overall survival. Conclusion: Age alone should not be an exclusion criterion for consideration of PD. With careful selection, PD can be safely performed in octogenarians. Elderly patients should be referred to a specialized unit for an objective assessment to determine the suitability for this aggressive but potential curative approach.

Variations in intrinsic breast cancer characteristics in screen-detected breast cancer patients aged between 45 and 69 and above the age of 70.

BACKGROUND: Increasing age is a well-recognized risk factor for breast cancer. With an increase in life expectancy of women, more older patients are diagnosed with breast cancer. This study aimed to identify the variations in breast cancer attributes and mortality in different age groups in New Zealand. METHODS: This was a retrospective study of data from the Auckland Breast Cancer Register between 1 June 2000 and 28 February 2017. Patients who were diagnosed through Breast Screen were included. Group A included those aged between 45 and 69 years. Group B included individuals with an age of 70 years or above. RESULTS: From June 2000 to February 2017, a total of 6304 new cases of new breast cancer were diagnosed through Auckland Breast Screen, with 5788 patients in group A and 516 patients in group B. Group B was more likely to have the lower grade invasive cancers, with fewer grade 3 cancers. Oestrogen receptor positivity was more pronounced in group B, along with progesterone receptor positivity. Conversely, HER-2 receptor was less likely to be positive in group B. There was a significantly higher breast cancer-related mortality in group B (6.0% versus 2.7%). Mortality related to other causes was also much higher in group B as compared to that in group A (12.8% versus 2.5%). CONCLUSION: Women aged 70 years or above generally tend to have a more favourable type of breast cancer, with a lower tumour grade, oestrogen and progesterone receptor positivity, and lower rate of HER-2 overexpression.

Stemness Related Genes Revealed by Network Analysis Associated With Tumor Immune Microenvironment and the Clinical Outcome in Lung Adenocarcinoma.

Lung adenocarcinoma (LUAD) is one of the leading fatal malignancy with high morbidity and mortality worldwide. However, due to its complicated mechanism and lack of effective clinical therapeutics, early diagnosis and prognosis are still unsatisfactory. Most of the previous studies focused on cancer stem cells (CSCs), the relationship between cancer stemness (stem-like characteristics) and anti-tumor immunity has not been clearly revealed. Therefore, this study aimed to comprehensively analyze the role of cancer stemness and tumor microenvironment (TME) in LUAD using weighted gene co-expression network analysis (WGCNA). We constructed a gene co-expression network, identified key modules, and hub genes, and further explored the relationship between hub gene expression and cancer immunological characteristics through a variety of algorithms, including Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) and Gene Set Enrichment Analysis (GSEA). The hub genes were renamed stemness related genes (SRGs), whose functions were examined at the transcription and protein levels through survival analysis with additional samples, Oncomine database, immunohistochemistry, single cell RNA sequencing (scRNA-seq) and single-sample Gene Set Enrichment Analysis (ssGSEA). Subsequently, Tumor Immune Dysfunction and Exclusion (TIDE) and Connectivity Map (CMap) were implemented for treatment and prognosis analyses. As a result, 15 co-expressed SRGs (CCNA2, CCNB1, CDC20, CDCA5, CDCA8, FEN1, KIF2C, KPNA2, MCM6, NUSAP1, RACGAP1, RRM2, SPAG5, TOP2A, and TPX2) were identified. The overexpression of which was discovered to be associated with reduced immune infiltration in LUAD. It was discovered that there was a general negative correlation between cancer stemness and immunity. The expression of SRGs could probably affect our tumor occurrence, progression, the efficacy of chemotherapy and immunotherapy, and clinical outcomes. In conclusion, the 15 SRGs reported in our study may be used as potential candidate biomarkers for prognostic indicators and therapeutic targets after further validation.

Integrative Models of Histopathological Image Features and Omics Data Predict Survival in Head and Neck Squamous Cell Carcinoma.

BACKGROUND: Both histopathological image features and genomics data were associated with survival outcome of cancer patients. However, integrating features of histopathological images, genomics and other omics for improving prognosis prediction has not been reported in head and neck squamous cell carcinoma (HNSCC). METHODS: A dataset of 216 HNSCC patients was derived from the Cancer Genome Atlas (TCGA) with information of clinical characteristics, genetic mutation, RNA sequencing, protein expression and histopathological images. Patients were randomly assigned into training (n = 108) or validation (n = 108) sets. We extracted 593 quantitative image features, and used random forest algorithm with 10-fold cross-validation to build prognostic models for overall survival (OS) in training set, then compared the area under the time-dependent receiver operating characteristic curve (AUC) in validation set. RESULTS: In validation set, histopathological image features had significant predictive value for OS (5-year AUC = 0.784). The histopathology + omics models showed better predictive performance than genomics, transcriptomics or proteomics alone. Moreover, the multi-omics model incorporating image features, genomics, transcriptomics and proteomics reached the maximal 1-, 3-, and 5-year AUC of 0.871, 0.908, and 0.929, with most significant survival difference (HR = 10.66, 95%CI: 5.06-26.8, p < 0.001). Decision curve analysis also revealed a better net benefit of multi-omics model. CONCLUSION: The histopathological images could provide complementary features to improve prognostic performance for HNSCC patients. The integrative model of histopathological image features and omics data might serve as an effective tool for survival prediction and risk stratification in clinical practice.

Exploration and validation of the effects of robust co-expressed immune-related genes on immune infiltration patterns and prognosis in laryngeal cancer.

OBJECTIVES: Laryngeal cancer is a common malignant tumor that originates from the larynx, yet its molecular mechanisms have not been thoroughly explored. The purpose of this study was to identify and evaluate immune-related genes in laryngeal cancer through gene co-expression networks, which may serve as biomarkers for its immunotherapy. METHODS: We applied ESTIMATE to evaluate the immune-infiltration landscape of tumor microenvironment. The co-expression networks were constructed by weighted gene co expression network analysis (WGCNA) and compared with the existing human immune related genes (IRGs) to determine the co-expressed IRGs. GSVA combined with CIBERSORT and ssGSEA illustrated the correlation of hub genes and immune infiltration patterns. TIDE algorithm and Subclass mapping evaluated the function of hub genes in predicting immune function and immunotherapeutic sensitivity. The pRRophetic was employed in the sensitivity prediction of chemotherapeutic drugs. RESULTS: A total of 23 co-expressed IRGs were identified and showed robust expression characteristics. These genes were significantly related to immune infiltration patterns, immune function and sensitivity prediction of immunotherapy and chemotherapeutic drugs for laryngeal cancer patients. Genetic alteration in somatic mutation level and related pathways were also revealed. CONCLUSION: The 23 co-expressed IRGs may act as immunotherapeutic biomarkers and potential therapeutic targets for laryngeal cancer with certain expression robustness. The molecular mechanisms deserve further investigation, which will guide clinical treatment in the future.

Predictors for complete pathological response for stage II and III rectal cancer following neoadjuvant therapy - A systematic review and meta-analysis.

BACKGROUND: There has been an increasing interest in the complete pathological response (pCR) in rectal cancers following neoadjuvant therapy. The aim of this study was to identify predictive factors of pCR in locally advanced rectal cancer following neoadjuvant therapy. METHODS: The studies identified were appraised with standard selection criteria. The selection criteria included studies on patients with stage II or III rectal cancer who underwent neoadjuvant therapy. RESULTS: Patients with pCR are more likely to be older (p = 0.0002), have cancers closer distance to the anal verge (p < 0.00001), smaller tumors (P < 0.0001), no clinical lymph nodes involvement (p=<0.00001) and waited more than eight weeks until definitive surgery (p = 0.002). There was no difference in gender (p = 0.15) and tumor differentiation (p = 0.21). CONCLUSIONS: The 'Watch and Wait' approach may be appropriate for selected patients. Patients with lower rectal cancers, smaller tumors, and negative clinical lymph node involvement may be more likely to achieve pCR following neoadjuvant therapy.

Intraoperative macroscopic tumour consistency is associated with overall survival after cytoreductive surgery and intraperitoneal chemotherapy for appendiceal adenocarcinoma with peritoneal metastases: A retrospective observational study.

BACKGROUND: This study examines the impact of intraoperative macroscopic tumour consistency on short-term and long-term outcomes after cytoreductive surgery (CRS) with intraperitoneal chemotherapy (IPC) for appendiceal adenocarcinoma with peritoneal metastases. METHODS: Macroscopic intraoperative tumour consistency was classified in three groups as soft (jelly-like geltatinous tumours), hard (hard tumour nodules without gelatinous features) and intermediate (both soft and hard features). In-hospital mortality, major morbidity, intensive care unit (ICU), high dependency unit (HDU) and total hospital stay, disease-free survival (DFS) and overall survival (OS) were compared. RESULTS: The three groups had similar perioperative short-term outcomes. Patients with soft, intermediate and hard tumours revealed differences in OS (p < 0.001) and DFS (p = 0.03). Multivariable analysis revealed a shorter OS for patients with hard versus soft tumours (HR for hard tumours = 4.43, 95%CI 2.19-9.00). CONCLUSIONS: Intraoperative macroscopic tumour consistency may be used as a prognostic marker for survival in patients with appendiceal adenocarcinoma with peritoneal metastases.

Survival difference between mucinous vs. non-mucinous colorectal cancer following cytoreductive surgery and intraperitoneal chemotherapy.

BACKGROUND: It is believed that the oncologic behavior of mucinous colorectal adenocarcinoma (MC) is different from non-mucinous adenocarcinoma (NMC). The aim of the study is to compare long-term survivals between patients with MC and those with NMC following cytoreductive surgery (CRS) and intraperitoneal chemotherapy (IPC). METHODS: This was a retrospective study of prospectively collected data of patients with peritoneal metastases of colorectal origin following CRS and IPC. Group I included patients with MC which was defined as being composed of >50% extracellular mucin. Group II included those with NMC. Subgroup analysis was performed according to the location of primary tumor. RESULTS: A total of 213 patients were included in this study. The two groups had similar hospital mortality, high dependency unit stay. MC group had a significantly longer mean intensive care unit (ICU) stay (p = .037) and total hospital stay (p = .037). There was no significant difference in overall survival (OS) and disease-free survival (DFS) between two groups (p = .657 and p = .938, respectively). Multivariate analysis showed that the presence of mucin was not an independent negative prognostic factor for OS (p = .190). CONCLUSION: In summary, patients with MC had a similar long-term survival outcome with those with NMC following CRS and IPC.

Discrimination, Bullying and Harassment in Surgery: A Systematic Review and Meta-analysis.

BACKGROUND: In 2015, the public media in Australia reported a series of life stories of victims who had been subjected to inappropriate behaviors in their surgical careers, bringing the profession into disrepute. Currently, limited data are available in the medical literature on discrimination, bullying and harassment (DBH) in surgery. This significant information gap prompted a systematic review to compile relevant information about DBH in surgical practice and training, in particular, its prevalence and impact. METHODS: A literature search was conducted using the MEDLINE, EMBASE and PubMed databases (May 1929-October 2017). Studies identified were appraised with standard selection criteria. Data points were extracted, and meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. RESULTS: Eight studies, comprising 5934 participants, were examined. Discrimination occurred in a pooled estimate of 22.4% [95% Confidence Interval (CI) = 14.0-33.9%]. One of the papers reported the prevalence of bullying using two methods including Revised Negative Acts Questionnaire and a definition by Einarsen. Pooled estimate of incidence rate was thus 37.7% (95% CI = 34.0-41.5%) and 40.3% (95% CI = 34.7-46.2%), respectively. In terms of harassment, pooled prevalence was 31.2% (95% CI = 10.0-65.0%). CONCLUSIONS: DBH is a significant issue in surgery. The true incidence of these issues may remain underestimated. Actions are being taken by professional bodies to create a positive culture in surgery. The effectiveness of these strategies is yet to be determined. More studies are warranted to investigate the magnitude of these issues given their psychological impact, and more importantly to monitor the effectiveness of current measures.