Patient perspective on adapting to bowel dysfunction after rectal cancer surgery.

AIM: Bowel dysfunction continues to be a clinically significant consequence of rectal cancer surgery, affecting quality of life. Rectal cancer patients value self-empowerment and adaptation to change to improve their quality of life in the context of bowel dysfunction. There are limited qualitative data addressing patients' perspectives on adapting to bowel dysfunction. The aim of this study is to evaluate patients' perspectives on adapting to bowel dysfunction after rectal cancer surgery. METHOD: Adult patients who underwent rectal cancer surgery with sphincter preservation at a single colorectal referral centre from July 2017 to July 2020 were included. Patients were excluded if they had surgery <1 year since recruitment, received a permanent stoma or developed recurrence or metastasis. Semistructured interviews were held by phone and transcribed verbatim. Bowel dysfunction was assessed via the low anterior resection syndrome (LARS) score. Thematic analysis was used to identify adaptations which patients found helpful for improving bowel dysfunction after rectal cancer surgery. RESULTS: A total of 54 patient interviews were included. The distribution of patients with no, minor and major LARS was 39%, 22% and 39%, respectively. Four main themes were conceived from the analysis: implementing lifestyle changes, fostering supportive relationships and self-compassion, communication and access to resources, and adapting to social and cultural challenges. Associated subthemes were identified, namely forward planning, self-compassion and addressing social stigma. CONCLUSION: Patients' valuable perspective on adapting to bowel dysfunction involve subtle themes which expand the existing literature. These themes inform a patient-centred approach, which may improve outcomes and quality of care for rectal cancer patients.

A transformable and self-oxygenated smart probe for enhanced tumor sonodynamic therapy.

Sonodynamic therapy (SDT) is emerging as a promising modality for cancer treatment. However, improving the tumor bioavailability and anti-hypoxia capability of sonosensitizers faces a big challenge. In this work, we present a tumor microenvironment (TME)-mediated nanomorphology transformation and oxygen (O2) self-production strategy to enhance the sonodynamic therapeutic efficacy of tumors. A smart probe Ce6-Leu@Mn2+ that consists of a glutathione (GSH) and leucine amino peptidase (LAP) dual-responsive unit, a 2-cyanobenzothiazole (CBT) group, and a Mn2+-chelated Ce6 as sonosensitizer for tumor SDT was synthesized, and its SDT potential for liver tumor HepG2 in living mice was systematically studied. It was found that the probes could self-assemble into large nanoparticles in physiological condition and spontaneously transformed into small particles under the dual stimulation of GSH and LAP in TME resulting in enhanced tumor accumulation and deep penetration. More notably, Ce6-Leu@Mn2+ could convert endogenous hydrogen peroxide to O2, thereby alleviating the hypoxia and achieving effective SDT against hypoxic tumors under the excitation of ultrasound. We thus believe this smart TME-responsive probe may provide a noninvasive and efficient means for malignant tumor treatment. STATEMENT OF SIGNIFICANCE: Sonodynamic therapy (SDT) is emerging as a promising therapeutic modality for cancer treatment. However, how to improve the tumor bioavailability and anti-hypoxia capability of sonosensitizers remains a huge challenge. Herein, we rationally developed a theranostic probe Ce6-Leu@Mn2+ that can transform into small-size nanoparticles from initial large particles under the dual stimulation of LAP and GSH in tumor microenvironment (TME) resulting in enhanced tumor accumulation, deep tissue penetration as well as remarkable O2 self-production for enhanced sonodynamic therapy of human liver HepG2 tumor in living mice. This smart TME-responsive probe may provide a noninvasive and efficient means for hypoxic tumor treatment.

How well do we measure the impact of bowel dysfunction on health-related quality of life after rectal cancer surgery?

BACKGROUND: Rectal cancer surgery risks causing bowel dysfunction, which has an important impact on health-related quality of life. The validity of generic tools used to measure health-related quality of life after bowel dysfunction is unclear. This study aimed to determine the content validity of health-related quality-of-life measurement tools in rectal cancer. METHODS: This was a qualitative single-center study in which adult patients who underwent rectal cancer surgery with sphincter preservation from July 2017 to October 2020 were recruited. Patients were excluded if they developed local metastasis, required a permanent stoma, or had surgery <1 year since recruitment. Telephone-based semi-structured interviews were conducted. Bowel dysfunction was measured using the Low Anterior Resection Syndrome score. Content analysis was achieved using the International Classification of Functioning framework. RESULTS: Recurrent bowel dysfunction-related concepts included "Mental functions," "Defecation functions," "Emotional functions," "Recreation and leisure," "Intimate relationships," and "Remunerative employment." A mean of 7.5 recurrent bowel dysfunction-related concepts were identified within the health-related quality of life instruments analyzed. The European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire-C30 (n = 11) and the 36-Item Short Form Health Survey (n = 9) covered the greatest number of recurrent bowel dysfunction-related concepts. Concepts such as "Mental functions," "Urination functions," "Sexual functions," "Driving," and "Mobility" were not covered by any instrument. CONCLUSION: The content of traditional health-related quality-of-life instruments is missing important areas that represent the impact of bowel dysfunction after rectal cancer surgery on health-related quality of life. These findings could help improve patient-centered care in rectal cancer surgery.

Efficacy of the combination of Chinese herbal medicine and negative pressure wound therapy in the treatment of patients with diabetic foot ulcer: A meta-analysis.

This study aimed to systematically evaluate the clinical efficacy of Chinese herbal medicine combined with negative pressure wound therapy (NPWT) in the treatment of diabetic foot ulcers (DFU). Computerised searches of the China National Knowledge Infrastructure, Wanfang, Chinese BioMedical Literature Database, PubMed, Cochrane Library and Embase databases were conducted for randomised controlled trials on the use of Chinese herbal medicines combined with NPWT for the treatment of DFU. The search period ranged from the time of establishment of each database to July 2023. Literature screening and data extraction were performed independently by two investigators, and the quality of the included studies was assessed. The meta-analysis was performed using Review Manager 5.4 software. A total of 25 studies were analysed, including 1777 DFUs, with 890 and 887 patients in the experimental and control groups, respectively. The results showed that the treatment of DFUs with a Chinese herbal medicine in combination with NPWT increased the overall effectiveness (odds ratio [OR] = 4.32, 95% confidence interval [CI]: 2.96-6.30, p < 0.001), wound healing rate (mean difference [MD] = 18.35, 95% CI: 13.07-23.64, p < 0.001) and ankle brachial index (MD = 0.10, 95% CI: 0.06-0.14, p < 0.001); reduced the wound healing time (MD = -11.01, 95% CI: -13.25 to -8.78, p < 0.001) and post-treatment wound area (MD = -1.73, 95% CI: -2.46 to -1.01, p < 0.001); decreased the C-reactive protein level (MD = -3.57, 95% CI: -5.13 to -2.00, p < 0.001); and increased vascular endothelial growth factor level (MD = 19.20, 95% CI: 8.36-30.05, p < 0.001). Thus, Chinese herbal medicines combined with NPWT can effectively promote wound healing, reduce inflammation and shorten the disease course in patients with DFU, while demonstrating precise clinical efficacy.

Predictive Factors for Successful Same-Day Discharge After Minimally Invasive Colectomy and Stoma Reversal.

BACKGROUND: Same-day discharge after minimally invasive colorectal surgery is a safe, effective practice in specific patients that can enhance the efficiency of enhanced recovery pathways. OBJECTIVE: To identify predictive factors associated with success or failure of same-day discharge. DESIGN: Prospective cohort study from January 2020 to March 2023. SETTINGS: Tertiary colorectal center. PATIENTS: Adult patients eligible for same-day discharge with remote postdischarge follow-up included those with minimal comorbidities, residing near the hospital, having sufficient home support, and owning a mobile device. INTERVENTIONS: Patients were discharged on the day of surgery upon meeting specific criteria, including adequate pain control, tolerance of oral intake, independent mobility, urination, and the absence of complications. Successful same-day discharge was defined as discharge on the day of surgery without unplanned visits in the first 72 hours. MAIN OUTCOME MEASURES: Factors associated with successful or failed same-day discharge after minimally invasive colorectal surgery. RESULTS: A total of 175 patients (85.3%) were discharged on the day of surgery, with 14 patients (8%) having an unplanned visit within 72 hours. Overall, 161 patients (78.5%) were categorized as same-day discharge success and 44 patients (21.5%) as same-day discharge failure. The same-day discharge failure group had a higher Charlson Comorbidity Index (3.7 vs 2.8, p = 0.03). Mean length of stay (0.8 vs 3.0, p = 0.00), 30-day complications (10% vs 48%, p = 0.00), and readmissions (8% vs 27%, p = 0.00) were higher in the same-day discharge failure group. Regression analysis showed that failed same-day discharge was associated with higher comorbidities (OR 0.79; 95% CI, 0.66-0.95) and prolonged postanesthesia care unit time (OR 0.99; 95% CI, 0.99-0.99). Individuals who received a regional nerve block (OR 4.1; 95% CI, 1.2-14) and those who did not consume postoperative opioids (OR 4.6; 95% CI, 1-21) were more likely to have successful same-day discharge. LIMITATIONS: Single-center study. CONCLUSIONS: Our findings indicate that comorbidities and prolonged postanesthesia care unit stays were associated with same-day discharge failure, whereas regional nerve blocks and minimal postoperative opioids were related to success. These factors may inform future research aiming to enhance colorectal surgery recovery protocols. See Video Abstract . FACTORES PREDICTIVOS PARA UN ALTA EXITOSA EL MISMO DA DESPUS DE UNA COLECTOMA MNIMAMENTE INVASIVA Y REVERSIN DEL ESTOMA: ANTECEDENTES:El alta el mismo día después de una cirugía colorrectal mínimamente invasiva es una práctica segura y eficaz en pacientes específicos que puede mejorar la eficiencia de las vías de recuperación mejoradas.OBJETIVO:Identificar factores predictivos asociados con el éxito o fracaso del alta el mismo día.DISEÑO:Estudio de cohorte prospectivo del 01/2020 al 03/2023.AJUSTES:Centro colorrectal terciario.PACIENTES:Los pacientes adultos elegibles para el alta el mismo día con seguimiento remoto posterior al alta incluyeron aquellos con comorbilidades mínimas, que residían cerca del hospital, tenían suficiente apoyo en el hogar y poseían un dispositivo móvil.INTERVENCIONES:Los pacientes fueron dados de alta el día de la cirugía al cumplir con criterios específicos, incluido un control adecuado del dolor, tolerancia a la ingesta oral, movilidad independiente, micción y ausencia de complicaciones. El alta exitosa el mismo día se definió como el alta el día de la cirugía sin visitas no planificadas en las primeras 72 horas.PRINCIPALES MEDIDAS DE RESULTADO:Factores asociados con el alta exitosa o fallida el mismo día después de una cirugía colorrectal mínimamente invasiva.RESULTADOS:Un total de 175 (85,3%) pacientes fueron dados de alta el día de la cirugía y 14 (8%) pacientes tuvieron una visita no planificada dentro de las 72 horas. En total, 161 (78,5%) pacientes se clasificaron como éxito del alta el mismo día y 44 (21,5%) pacientes como fracaso del alta el mismo día. El grupo de fracaso del alta el mismo día tuvo un índice de comorbilidad de Charlson más alto (3,7, 2,8, p = 0,03). La duración media de la estancia hospitalaria (0,8, 3,0, p = 0,00), las complicaciones a los 30 días (10%, 48%, p = 0,00) y los reingresos (8%, 27%, p = 0,00) fueron mayores en el mismo día grupo de fallo de descarga. El análisis de regresión mostró que el alta fallida el mismo día se asoció con mayores comorbilidades (OR 0,79; IC del 95 %: 0,66; 0,95) y tiempo prolongado en la unidad de cuidados postanestésicos (OR 0,99; IC del 95 %: 0,99; 0,99). Las personas que recibieron un bloqueo nervioso regional (OR 4,1; IC del 95 %: 1,2, 14) y aquellos que no consumieron opioides posoperatorios (OR 4,6, IC del 95 %: 1-21) tuvieron más probabilidades de tener éxito en el mismo día -descarga.LIMITACIONES:Estudio unicéntrico.CONCLUSIONES:Nuestros hallazgos indican que las comorbilidades y las estancias prolongadas en la unidad de cuidados postanestésicos se asociaron con el fracaso del alta el mismo día, mientras que los bloqueos nerviosos regionales y los opioides postoperatorios mínimos se relacionaron con el éxito. Estos factores pueden informar investigaciones futuras destinadas a mejorar los protocolos de recuperación de la cirugía colorrectal. (Traducción-Yesenia Rojas-Khalil ).

Effect of Feedback Modality on Simulated Surgical Skills Learning Using Automated Educational Systems- A Four-Arm Randomized Control Trial.

OBJECTIVE: To explore optimal feedback methodologies to enhance trainee skill acquisition in simulated surgical bimanual skills learning during brain tumor resections. HYPOTHESES: (1) Providing feedback results in better learning outcomes in teaching surgical technical skill when compared to practice alone with no tailored performance feedback. (2) Providing more visual and visuospatial feedback results in better learning outcomes when compared to providing numerical feedback. DESIGN: A prospective 4-parallel-arm randomized controlled trial. SETTING: Neurosurgical Simulation and Artificial Intelligence Learning Centre, McGill University, Canada. PARTICIPANTS: Medical students (n = 120) from 4 Quebec medical schools. RESULTS: Participants completed a virtually simulated tumor resection task 5 times while receiving 1 of 4 feedback based on their group allocation: (1) practice-alone without feedback, (2) numerical feedback, (3) visual feedback, and (4) visuospatial feedback. Outcome measures were participants' scores on 14-performance metrics and the number of expert benchmarks achieved during each task. There were no significant differences in the first task which determined baseline performance. A statistically significant interaction between feedback allocation and task repetition was found on the number of benchmarks achieved, F (10.558, 408.257)=3.220, p < 0.001. Participants in all feedback groups significantly improved their performance compared to baseline. The visual feedback group achieved significantly higher number of benchmarks than the practice-alone group by the third repetition of the task, p = 0.005, 95%CI [0.42 3.25]. Visual feedback and visuospatial feedback improved performance significantly by the second repetition of the task, p = 0.016, 95%CI [0.19 2.71] and p = 0.003, 95%CI [0.4 2.57], respectively. CONCLUSION: Simulations with autonomous visual computer assistance may be effective pedagogical tools in teaching bimanual operative skills via visual and visuospatial feedback information delivery.

Hafnium (Hf)-Chelating Porphyrin-Decorated Gold Nanosensitizers for Enhanced Radio-Radiodynamic Therapy of Colon Carcinoma.

X-ray-induced radiodynamic therapy (RDT) that can significantly reduce radiation dose with an improved anticancer effect has emerged as an attractive and promising therapeutic modality for tumors. However, it is highly significant to develop safe and efficient radiosensitizing agents for tumor radiation therapy. Herein, we present a smart nanotheranostic system FA-Au-CH that consists of gold nanoradiosensitizers, photosensitizer chlorin e6 (Ce6), and folic acid (FA) as a folate-receptor-targeting ligand for improved tumor specificity. FA-Au-CH nanoparticles have been demonstrated to be able to simultaneously serve as radiosensitizers and RDT agents for enhanced computed tomography (CT) imaging-guided radiotherapy (RT) of colon carcinoma, owing to the strong X-ray attenuation capability of high-Z elements Au and Hf, as well as the characteristics of Hf that can transfer radiation energy to Ce6 to generate ROS from Ce6 under X-ray irradiation. The integration of RT and RDT in this study demonstrates great efficacy and offers a promising therapeutic modality for the treatment of malignant tumors.

Outcome of Facial Burn Injuries Treated by a Nanofibrous Temporary Epidermal Layer.

BACKGROUND: The face is commonly affected in thermal injuries, with a demand for proper recognition and the correct choice of treatment to guarantee optimal aesthetic and functional outcomes. It is highly vascularized and often heals conservatively, highlighting the particular relevance of conservative treatment modalities, many of which require daily re-applications or dressing changes, which can be painful and tedious for both the patient and the healthcare providers. Motivated by encouraging results of a novel temporary nanofibrous epidermal layer, we herein present a case series of this technology in a case series of patients suffering from facial burns and treated in our Burn Center. PATIENTS AND METHODS: Patients with superficial partial-thickness facial burns and mixed pattern burns, which were treated with SpinCare™, an electrospun nanofibrous temporary epidermal layer, between 2019 and 2021, at our institution were analyzed retrospectively. The Manchester scar scale (MSS) and numeric rating scale (NRS) were used for scar, pain, and outcome evaluation at different time points by five independent board-certified plastic surgeons with profound experience in burn surgery. RESULTS: Ten patients (m = 9; f = 1) were treated and evaluated retrospectively. The mean age was 38.8 ± years (SD ± 17.85). The mean healing time was 6.4 days (SD ± 1.56). The mean follow-up was 16.4 months (SD ± 11.33). The mean MSS score was 5.06 (SD ± 1.31), and the mean NRS Score for pain was significantly reduced from initially 7 to 0.875 upon application (mean (pre-application) 7 ± 0.7 and (application) 0.875 ± 1.26; p ≤ 0.0001). Patients reported a NRS score of 10 in terms of functional and cosmetic outcomes at their final follow-up appointment. No adverse effects were observed. CONCLUSIONS: The application of a nanofibrous temporary epidermal layer such as SpinCare™ represents a relatively easy-to-use, well-tolerated, and effective alternative for the treatment of partial-thickness facial burns.

B-cell prolymphocytic leukemia with P53 abnormalities successfully treated with bendamustine and rituximab: a report of three cases.

Background: B-cell prolymphocytic leukemia (B-PLL) is a rare mature B-cell tumor with an aggressive clinical course and poor prognosis. It is characterized by prominent splenomegaly and prolymphocytes exceeding 55% of the lymphoid cells in the blood. Purine analog-based chemo-immunotherapy is the first-line therapy for B-PLL. Owing to its rarity, there are few reports on the efficacy of bendamustine and rituximab (BR) regimen. Our study presents three cases of BR being effective in the treatment of B-PLL and provides experience for clinical treatment. Case Description: This report describes the cases of three male patients (median age: 66 years old) who initially presented with abdominal discomfort. Physical examinations and imaging revealed splenomegaly, while a peripheral blood (PB) smear revealed a prolymphocyte count exceeding 70% of the lymphoid cells. Therefore, the three patients were diagnosed with B-PLL. Further molecular detection showed that they harbored P53 abnormalities (17p deletion/TP53 mutation) associated with resistance to conventional chemotherapies. In addition, one of the patients had a highly complex karyotype and multiple gene mutations. All patients underwent four cycles of BR, and two of them received two further cycles of rituximab monotherapy. Ultimately, the patients achieved a complete response (CR) that lasted for 25, 33, and 34 months, respectively, with a median follow-up time of 34 months. The adverse events of the BR mainly included a grade 3 haematological toxicities. Also, the treatment was well-tolerated. Conclusions: This case series suggests that BR regimen is promising for bringing deep remission to patients with B-PLL. Prospective trials are still required for further elucidation.

Light-initiated aggregation of gold nanoparticles for synergistic chemo-photothermal tumor therapy.

The combination of chemotherapy with photothermal therapy (PTT) has attracted extensive attention due to its excellent synergetic effect attributing to the fact that hyperthermia can effectively promote the tumor uptake of chemotherapeutic drugs. Herein, we propose a light-initiated gold nanoparticle (AuNP) aggregation boosting the uptake of chemotherapeutic drugs for enhanced chemo-photothermal tumor therapy. Novel light-responsive AuNPs (tm-AuNPs) were rationally designed and fabricated by conjugating both 2,5-diphenyltetrazole (Tz) and methacrylic acid (Ma) onto the surface of AuNPs with small size (∼20 nm). Upon the irradiation of 405 nm laser, AuNPs could be initiated to form aggregates specifically within tumors through the covalent cycloaddition reaction between Tz and Ma. Taking advantage of the controllable photothermal effect of Au aggregates under NIR excitation, improved enrichment of doxorubicin (DOX) in tumor tissues was realized, combined with PTT, resulting in outstanding synergetic anti-tumor efficacy in living mice. We thus believe that this light-initiated AuNP aggregation approach would offer a valuable and powerful tool for precisely synergistic chemo-photothermal tumor therapy.

Evaluating glioblastoma tumour sphere growth and migration in interaction with astrocytes using 3D collagen-hyaluronic acid hydrogels.

Glioblastoma (GB) is an astrocytic brain tumour with a low survival rate, partly because of its highly invasive nature. The GB tumour microenvironment (TME) includes its extracellular matrix (ECM), a variety of brain cell types, unique anatomical structures, and local mechanical cues. As such, researchers have attempted to create biomaterials and culture models that mimic features of TME complexity. Hydrogel materials have been particularly popular because they enable 3D cell culture and mimic TME mechanical properites and chemical composition. Here, we used a 3D collagen I-hyaluronic acid hydrogel material to explore interactions between GB cells and astrocytes, the normal cell type from which GB likely derives. We demonstrate three different spheroid culture configurations, including GB multi-spheres (i.e., GB and astrocyte cells in spheroid co-culture), GB-only mono-spheres cultured with astrocyte-conditioned media, and GB-only mono-spheres cultured with dispersed live or fixed astrocytes. Using U87 and LN229 GB cell lines and primary human astrocytes, we investigated material and experiment variability. We then used time-lapse fluorescence microscopy to measure invasive potential by characterizing the sphere size, migration capacity, and weight-averaged migration distance in these hydrogels. Finally, we developed methods to extract RNA for gene expression analysis from cells cultured in hydrogels. U87 and LN229 cells displayed different migration behaviors. U87 migration occurred primarily as single cells and was reduced with higher numbers of astrocytes in both multi-sphere and mono-sphere plus dispersed astrocyte cultures. In contrast, LN229 migration exhibited features of collective migration and was increased in monosphere plus dispersed astrocyte cultures. Gene expression studies indicated that the most differentially expressed genes in these co-cultures were CA9, HLA-DQA1, TMPRSS2, FPR1, OAS2, and KLRD1. Most differentially expressed genes were related to immune response, inflammation, and cytokine signalling, with greater influence on U87 than LN229. These data show that 3D in vitro hydrogel co-culture models can be used to reveal cell line specific differences in migration and to study differential GB-astrocyte crosstalk.

NIR Light-Mediated Mitochondrial RNA Modification for Cancer RNA Interference Therapeutics.

Mitochondrial RNA (mtRNA) plays a critical role in synthesis of mitochondrial proteins. Interfering mtRNA is a highly effective way to induce cell apoptosis. Herein, we report a near-infrared (NIR) light-mediated mitochondrial RNA modification approach for long-term imaging and effective suppression of tumors. A tumor-targetable NIR fluorescent probe f-CRI consisting of a cyclic RGD peptide, a NIR fluorophore IR780, and a singlet oxygen (1 O2 )-labile furan group for RNA modification was rationally designed and synthesized. This probe was demonstrated to dominantly accumulate in cellular mitochondria and could be covalently conjugated onto mtRNA upon 808 nm irradiation resulting in prolonged retention in tumors. More notably, this covalent modification of mtRNA by f-CRI could perturb the function of mitochondria leading to remarkable tumor suppression. We thus envision that our current approach would offer a potential approach for cancer RNA interference therapeutics.

A tumor-targetable NIR probe with photoaffinity crosslinking characteristics for enhanced imaging-guided cancer phototherapy.

Spatiotemporally manipulating the in situ immobilization of theranostic agents within cancer cells to improve their bioavailability is highly significant yet challenging in tumor diagnosis and treatment. Herein, as a proof-of concept, we for the first time report a tumor-targetable near-infrared (NIR) probe DACF with photoaffinity crosslinking characteristics for enhanced tumor imaging and therapeutic applications. This probe possesses great tumor-targeting capability, intensive NIR/photoacoustic (PA) signals, and a predominant photothermal effect, allowing for sensitive imaging and effective photothermal therapy (PTT) of tumors. Most notably, upon 405 nm laser illumination, DACF could be covalently immobilized within tumor cells through a photocrosslinking reaction between photolabile diazirine groups and surrounding biomolecules resulting in enhanced tumor accumulation and prolonged retention simultaneously, which significantly facilitates the imaging and PTT efficacy of tumor in vivo. We therefore believe that our current approach would provide a new insight for achieving precise cancer theranostics.

S1PR1/S1PR3-YAP signaling and S1P-ALOX15 signaling contribute to an aggressive behavior in obesity-lymphoma.

BACKGROUND: Excess body weight has been found to associate with an increased risk of lymphomas and some metabolic pathways are currently recognized in lymphomagenesis. Bioactive lipid metabolites such as sphingosine-1-phosphate (S1P) have been proposed to play an important role linking obesity and lymphomas. However, the underlying mechanism(s) of S1P signaling in obesity-lymphomagenesis have not been well addressed. METHODS: The gene expression of sphingosine kinase (SPHK), lymphoma prognosis, and S1P production were analyzed using Gene Expression Omnibus (GEO) and human lymphoma tissue array. Obesity-lymphoma mouse models and lymphoma cell lines were used to investigate the S1P/SPHK-YAP axis contributing to obesity-lymphomagenesis. By using the mouse models and a monocyte cell line, S1P-mediated polarization of macrophages in the tumor microenvironment were investigated. RESULTS: In human study, up-regulated S1P/SPHK1 was found in human lymphomas, while obesity negatively impacted progression-free survival and overall survival in lymphoma patients. In animal study, obesity-lymphoma mice showed an aggressive tumor growth pattern. Both in vivo and in vitro data suggested the existence of S1P-YAP axis in lymphoma cells, while the S1P-ALOX15 signaling mediated macrophage polarization towards TAMs exacerbated the lymphomagenesis. In addition, treatment with resveratrol in obesity-lymphoma mice showed profound effects of anti-lymphomagenesis, via down-regulating S1P-YAP axis and modulating polarization of macrophages. CONCLUSION: S1P/S1PR initiated the feedback loops, whereby S1P-S1PR1/S1PR3-YAP signaling mediated lymphomagenesis contributing to tumor aggressive growth, while S1P-ALOX15 signaling mediated TAMs contributing to immunosuppressive microenvironment in obesity-lymphoma. S1P-targeted therapy could be potentially effective and immune-enhancive against obesity-lymphomagenesis.

Does the Low Anterior Resection Syndrome Score Accurately Represent the Impact of Bowel Dysfunction on Health-Related Quality of Life?

BACKGROUND: Bowel dysfunction after rectal cancer surgery is common, but its effect on health-related quality of life (HRQOL) is complex. Objective measures of bowel function may not be a good representation on the actual impact on HRQOL. Therefore, the objective of this study is to determine whether there are differences between patient-reported bowel-related impairment versus a standardized measure of bowel dysfunction on HRQOL. METHODS: A prospective database starting in September 2018 of adult patients who had undergone sphincter preserving rectal cancer surgery up to October 2021 was queried. Patients were excluded if they had local recurrence, metastasis, persistent stoma, or had less than 1-year follow-up. Patients were administered the study instruments at their standard surveillance visit: patient-reported bowel-related quality of life(BQOL) impairment, HRQOL using the Short Form-36 (SF-36), and bowel dysfunction using the low anterior resection syndrome(LARS) score. RESULTS: Overall, 136 patients were included. There were 43% with no LARS, 22% with minor LARS, and 35% with major LARS. For the BQOL, 26% of subjects reported no impairment, 57% minor impairment, and 17% major impairment. There was a high proportion of discordance between BQOL and LARS, with 23% minor or major LARS in patients with no BQOL impairment, and 32% with no or minor LARS with major BQOL impairment. The BQOL was associated with more changes in SF-36 scores compared to the LARS score. CONCLUSIONS: The patient-reported BQOL is likely to be a more relevant outcome of interest to patients than the objective LARS score. This has important implications for shared decision-making for rectal cancer treatments.

Predictors of pre- and post-treatment bowel dysfunction severity in patients with rectal cancer.

BACKGROUND: Treatment of rectal cancer is frequently associated with low anterior resection syndrome. However, data concerning the contribution rectal tumors have on pretreatment bowel-dysfunction is scarce. We sought to evaluate the impact of the untreated rectal cancer on bowel-dysfunction and the relationship of pretreatment and post-treatment function. METHODS: A prospective database of adults with rectal cancer at a single university-affiliated colorectal referral center from August 2018 to March 2022 was queried. Bowel-dysfunction was measured using the low anterior resection syndrome score questionnaire (categorized as no, minor, or major low anterior resection syndrome) which was provided to patients at their primary visit, and after treatment. Patients were included if they underwent rectal cancer treatment and had pre- and post-treatment low anterior resection syndrome measurements. Observed low anterior resection syndrome scores were compared to normative low anterior resection syndrome data for age and sex-specific distributions from published data. Multiple multinomial regression compared pre- and post-treatment low anterior resection syndrome scores. RESULTS: Overall, 121 patients were included with mean age 62.0 years (standard deviation 12.3), 74% male, and mean tumor height 8.7 cm (standard deviation 5.72). The proportion of pretreatment observed low anterior resection syndrome were 48% no low anterior resection syndrome, 28% minor, and 24% major. Male and older patients were more likely to have worse than predicted low anterior resection syndrome categories (P < .05). On average, low anterior resection syndrome category did not change after treatment (P = .618) and pretreatment low anterior resection syndrome category was a significant independent predictor of post-treatment category (P = .037). CONCLUSION: Pretreatment bowel-dysfunction in rectal cancer patients is common and significantly worse than predicted for older and male patients. Importantly, pretreatment bowel-dysfunction predicted postoperative function. These results may better inform the shared decision-making process.

A retrospective analysis of early discharge following minimally invasive colectomy in an enhanced recovery pathway.

BACKGROUND: There is increasing evidence to support discharge prior to gastrointestinal recovery following colorectal surgery. Furthermore, many patients are discharged early despite being excluded from an ambulatory colectomy pathway. The objective of this study was to determine the outcomes of patients discharged early following laparoscopic colectomy in an enhanced recovery pathway (ERP). METHODS: A retrospective review of all adult patients undergoing elective laparoscopic colectomy at a single university-affiliated colorectal referral center (08/2017-06/2021) was performed. Patients were included if they had undergone elective laparoscopic colectomy or ileostomy closure and excluded if they had been enrolled in an ambulatory colectomy pathway. Patients were then divided into three groups: LOS =1 day, LOS 2-3 days, and LOS 4+ days. The main outcomes were 30-day emergency room (ER) visits and readmissions. Reasons for inpatient stay per post-operative day (POD) were also recorded. RESULTS: A total of 497 patients were included [LOS1 n = 63 (13%), LOS2-3 n = 284 (57%), and LOS4+ n = 150 (30%)]. There were no differences in patient characteristics, diagnosis, or procedure between the groups. Patients were discharged with gastrointestinal recovery (GI-3) in 54% LOS1 vs. 98% LOS2-3 vs. 100% LOS4+ (p<0.001). Shorter procedure duration, transversus abdominus plane block, and lower opioid requirements were associated with shorter LOS (p<0.001). The absence of flatus was the most common reason to keep patients hospitalized: 61% on POD1, 21% on POD2, and 8% on POD3 (p<0.001). There were no differences in 30-day emergency visits, or readmission between the groups. In the LOS1 group, there were no differences in outcomes between patients with full return of bowel function at discharge compared to those without. CONCLUSION: Discharge on POD1 was not associated with increased emergency department use, complications, or readmissions. Importantly, full return of bowel function at discharge did not affect outcomes. There may be potential to expand eligibility criteria for ambulatory colectomy protocol.

Alkaline Phosphatase-Controllable and Red Light-Activated RNA Modification Approach for Precise Tumor Suppression.

RNA interference (RNAi) has proved to be a promising modality for disease treatment. However, the promise of conventional RNA therapeutics for clinical application is severely impeded by low delivery efficiency and susceptibility of RNAs to serum RNases. Therefore, developing advanced RNAi technology is an increasing demand for achieving precise medicine. Herein, for the first time, we propose an alkaline phosphatase (ALP)-controllable and red light-activated RNA modification (ALARM) approach for anti-tumor therapeutic application. An ALP-responsive NIR fluorogenic probe f-RCP consisting of a tumor-targeting cyclic RGD peptide, an ALP-activated photosensitizer CyOP, and an 1O2-susceptible furan module for RNA modification was rationally designed and synthesized. Studies have demonstrated that f-RCP can specifically target to liver carcinoma HepG2 cells and spontaneously emit activated NIR/photoacoustic signals upon cleavage by the ALP enzyme, allowing for sensitive detection of ALP-positive tumors. More notably, we surprisingly found that the capability of f-RCP producing singlet oxygen (1O2) under red light irradiation could be simultaneously unlocked, which can ignite the covalent cyclization reaction between furan and nucleobases of intracellular RNA molecules, leading to significant mitochondrial damage and severe apoptosis of tumor cells, in consequence realizing efficient tumor suppression. Most importantly, the potential therapeutic mechanism was first explored on the transcriptomic level. This delicate ALARM strategy may open up new insights into cancer gene therapy.

Variations in oral microbiome and its predictive functions between tumorous and healthy individuals.

Introduction. The oral cavity is one of the largest reservoirs of microorganisms and many pathogenic bacteria have been shown to be associated with the aetiology of oral cancers.Gap Statement. Owing to the complexity of oral microbial communities and their unclear relationship with oral cancer, identification of specific bacteria which contribute to oral cancer is a key imperative.Aim. To compare and investigate the variations in the composition of the bacterial microbiome and its functions between patients with oral tumorous lesions and healthy subjects.Methodology. Twenty-seven samples from individuals with oral tumours (five oral benign tumours and 22 oral squamous cell carcinomas) and 15 samples from healthy subjects were collected. Genomic DNA was extracted and the V3-V5 region of the 16S rRNA gene was sequenced. Subsequently, bioinformatic assessment was conducted using QIIME2, PICRUSt and linear discriminant analysis effect size analyses (LEfSe).Results. The oral microbiota was composed mainly of the phyla Proteobacteria (31.76 %, 35.00 %), Bacteroidetes (30.13 %, 25.13 %) and Firmicutes (23.92 %, 17.07 %) in tumorous and healthy individuals, respectively. Neisseria, Prevotella, Fusobacterium, Streptococcus, Capnocytophaga, Veillonella, Haemophilus, Prevotella, Porphyromonas and Leptotrichia were the most abundant genera. Alpha diversity in the tumour group was significantly greater than that in the healthy group (P<0.05). Differential analysis of microbes between groups demonstrated a significantly higher number of Neisseria, Veillonella, Streptococcus, Leptotrichia, Lautropia, Sphingopyxis, Sphingobium, Tannerella, Actinomyces and Rothia in healthy controls compared with the tumour group. However, the genera Treponema, Micrococcus, Pseudomonas, Janthinobacterium, Parvimos, Loktanella, Staphylococcus, Acinetobacter, Catonella, Aggregatibacter and Propionibacterium were significantly higher in the tumour group. Pathways related to cancers, cell motility, environmental adaptation, metabolism and signal transduction were enhanced in the tumour group, while functions associated with immune system diseases, replication, repair and translation were significantly enhanced in the healthy group.Conclusion. Variations in the oral microbiota and its functions showed a correlation with oral tumours. The tumour group showed an increased abundance of some multi-drug-resistant and periodontitis-related pathogens. The significantly altered microbiotas may serve as potential biomarkers or inform combination therapy for oral tumours.

A Comparison between Accurate Unilateral Puncture Paths Planned by Preoperative and Conventional Unilateral Puncture Techniques in Percutaneous Vertebroplasty.

Objective: Comparison of the clinical and radiological effects of precise unilateral puncture pathway prepared by preoperative CT data and traditional unilateral puncture pathway in PVP administration for the treatment of osteoporotic vertebral compression fractures. Summary of background data. PVP is a commonly used vertebral augmentation operation for the treatment of painful spinal compression fractures. A percutaneous unilateral approach is routinely used to get access to the vertebral body. PVP has had positive clinical results in a number of prior investigations. Numerous difficulties and issues, including puncture difficulty, radiation exposure, cement leakage, spinal cord or nerve damage, and intraspinal hematoma, have been described in contrast. Methods: This prospective study included 300 patients with single-level lumbar osteoporotic vertebral compression fractures, 180 females and 120 males, with an average age of 71.5 years. PVP was performed on randomized subjects using two distinct puncture procedures. The patients were separated into two groups: Preoperative planning, in which a precise unilateral puncture path was established using preoperative CT data, and Conventional planning, in which multiple puncture procedures were used. The participants were followed up on after surgery and mostly assessed on clinical and radiological results. The visual analogue scale for pain and the 36-item Short Form Health Survey (SF-36) questionnaire for health status were used to assess clinical outcomes. Radiation dosage, bone cement distribution, vertebral body height, and kyphotic angle were used to evaluate radiological results. Results: Participants remained monitored for 12 to 28 months on average. 151 individuals were treated with accurate unilateral puncture paths planned by preoperative CT data percutaneous vertebroplasty and 149 patients were treated with conventional unilateral paths percutaneous vertebroplasty. The Preoperative planning group's operation time and radiation dose were significantly lower than the Conventional group's; nevertheless, the volume of injected cement was significantly higher in the Preoperative steering committee than in the Conventional group. All patients in both groups had much less pain after the operations when compared to their preoperative suffering. There were no statistically significant variations between groups when the visual analogue scale and the 36-Item Short Form Health Survey were compared. Neither group showed a substantial decrease in the kyphotic angle during the follow-ups. In the Preoperative planning group, the kyphotic angle improved much more than in the Conventional group. At 1 month postoperatively, 16 patients in the Conventional group experienced apparent discomfort in the puncture sites because to facet joint violation. At the latest follow-up, all of the patients' discomfort had vanished after receiving local block therapy. Conclusion: Both preoperatively designed precise unilateral puncture pathways and traditional unilateral puncture procedures PVP are reasonably safe and effective for individuals with painful osteoporotic spinal compression fractures. Unilateral puncture courses planned via preoperative PVP, on the other hand, absorbed less radiation and operation time, as well as a good level of deformity correction and amount of injected cement, and caused less complications than traditional unilateral PVP.