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Gut May 2024Pancreatic ductal adenocarcinoma (PDAC) has limited therapeutic options, particularly with immune checkpoint inhibitors. Highly chemoresistant 'stem-like' cells, known...
OBJECTIVE
Pancreatic ductal adenocarcinoma (PDAC) has limited therapeutic options, particularly with immune checkpoint inhibitors. Highly chemoresistant 'stem-like' cells, known as cancer stem cells (CSCs), are implicated in PDAC aggressiveness. Thus, comprehending how this subset of cells evades the immune system is crucial for advancing novel therapies.
DESIGN
We used the KPC mouse model () and primary tumour cell lines to investigate putative CSC populations. Transcriptomic analyses were conducted to pinpoint new genes involved in immune evasion. Overexpressing and knockout cell lines were established with lentiviral vectors. Subsequent coculture assays, mouse and zebrafish tumorigenesis studies, and database approaches were performed.
RESULTS
Using the KPC mouse model, we functionally confirmed a population of cells marked by EpCAM, Sca-1 and CD133 as authentic CSCs and investigated their transcriptional profile. Immune evasion signatures/genes, notably the gene peptidoglycan recognition protein 1 (PGLYRP1), were significantly overexpressed in these CSCs. Modulating PGLYRP1 impacted CSC immune evasion, affecting their resistance to macrophage-mediated and T-cell-mediated killing and their tumourigenesis in immunocompetent mice. Mechanistically, tumour necrosis factor alpha (TNFα)-regulated PGLYRP1 expression interferes with the immune tumour microenvironment (TME) landscape, promoting myeloid cell-derived immunosuppression and activated T-cell death. Importantly, these findings were not only replicated in human models, but clinically, secreted PGLYRP1 levels were significantly elevated in patients with PDAC.
CONCLUSIONS
This study establishes PGLYRP1 as a novel CSC-associated marker crucial for immune evasion, particularly against macrophage phagocytosis and T-cell killing, presenting it as a promising target for PDAC immunotherapy.
PubMed: 38754953
DOI: 10.1136/gutjnl-2023-330995 -
JPRAS Open Jun 2024Scarless latissimus dorsi (LD) flap is a breast reconstruction technique, which allow to cover the lower pole of implant with a large portion of the LD muscle without...
INTRODUCTION
Scarless latissimus dorsi (LD) flap is a breast reconstruction technique, which allow to cover the lower pole of implant with a large portion of the LD muscle without skin paddle; it represents a surgical solution that transpose vascularized tissue avoiding the failure of breast reconstruction, following necrosis of mastectomy skin flaps.
MATERIAL AND METHOD
A retrospective review of patients undergoing immediate or delayed breast reconstruction using scarless LD flap reconstructions was performed. Clinical data obtained from follow-up visits were recorded. To evaluate breast shape contentment and patient satisfaction, the patients were requested to answer the Breast-Q, version 2.0 reduction module postoperative scales questionnaire at the 12-month follow-up.
RESULTS
We performed 19 scarless LD flap reconstructions between September 2019 and June 2022. The surgical time in average (considering minutes ± SD) was 130 (±15) minutes. The aesthetic assessment was good/excellent in 83% of patients. This was statistically significant (P=0.0).
CONCLUSIONS
The scarless LD flap reconstruction is a valid and reliable solution, which has the advantage to reduce the risk of exposed prosthesis if native skin necrosis occurs.
PubMed: 38601882
DOI: 10.1016/j.jpra.2024.03.004 -
Foods (Basel, Switzerland) Jan 2024Parboiling influences chemical compositions in rice grains. The objectives of this study were to evaluate the change in chemical content, total phenolic content and...
Parboiling influences chemical compositions in rice grains. The objectives of this study were to evaluate the change in chemical content, total phenolic content and antioxidant capacity of landrace rice genotypes under parboiling conditions and to identify the genotypes suitable for production of parboiled rice. Landrace rice varieties used in this study consisted of Glam Feang, Glam Tonkeaw, Kawgum, Glam Luem Phua, Medmakham, Deang Sakonnakhon, Sang Yod, Kawniewd-eang, Mali Deang, KDML105 and RD6. Parboiling reduced fiber content, total phenolic content and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging activity in rice grains. Fiber contents were 1.46% in brown rice (unpolished rice) and 1.40% in parboiled rice (24 h of soaking and 48 h of incubation). Total phenolic contents were 205.67 mg/100 g seed in brown rice and 35.34 mg/100 g seed in parboiled rice. Antioxidant capacity (DPPH) reduced from 68.45% in brown rice to 26.23% in parboiled rice. Ash content and protein content were not significantly affected by the parboiling process. Medmakham cv. had the highest total phenolic content and antioxidant capacity in brown rice and parboiled rice. Gum Leamphea cv. and Medmakham cv. were the best genotypes for ash content, protein content, total phenolic content and antioxidant capacity (DPPH) in brown rice and parboiled rice. Glam Feang cv. had the highest protein contents in brown rice and parboiled rice although it had low total phenolic content and antioxidant capacity. Cluster analysis further showed variation among genotypes, revealing distinct groupings in brown rice and parboiled rice based on chemical properties, phenolic content and antioxidant capacity. This research significantly contributes to a better understanding on how parboiling affects rice compositions and nutritional values. It emphasizes the importance of nuanced comprehension of how different rice varieties respond to parboiling, aiding informed decisions in rice processing and selection to meet specific nutritional needs.
PubMed: 38338528
DOI: 10.3390/foods13030393 -
Acta Obstetricia Et Gynecologica... Dec 2023Chronic pelvic pain (CPP) affects over one fifth of women worldwide, and endometriosis is one of the most common causes. In the present study, we examined whether sacral...
INTRODUCTION
Chronic pelvic pain (CPP) affects over one fifth of women worldwide, and endometriosis is one of the most common causes. In the present study, we examined whether sacral neuromodulation (SNM) is effective in the treatment of refractory chronic pelvic pain in women with endometriosis.
MATERIAL AND METHODS
This multicenter prospective pilot study was started in 2017 and includes patients with chronic pelvic pain with no other obvious pathology than endometriosis. Other treatment options have been tried or they are unsuitable. Patients underwent SNM implantation. The main outcome was postoperative pain reduction and secondary outcome was quality of life. The following questionnaires were used to assess the outcomes: Brief pain inventory (BPI), clinical global impression - improvement (CGI-I), 15D-measure of health-related quality of life, and Biberoglu and Behrman (B&B) score.
RESULTS
A total of 35 patients underwent the SNM procedure and, at the time of analysis, 15 patients had returned one-year questionnaires. The patients had a history of endometriosis for a median of 5.5 (interquartile range 2-9) years, with no correlation between the severity of symptoms and the duration of the disease (p = 0.158). A total of 31 patients (89%) were implanted with the internal pulse generator. There were statistically significant changes in BPI pain-related items. Worst experienced daily pain decreased among those who returned 12-month questionnaires from median 9 to 5 (p = 0.006), average daily pain from 6 to 3.5 (p = 0.004), and least daily pain from 3 to 1 (p = 0.004). Based on the CGI questionnaire (n = 14), at 12 months nine patients (60%) experienced great improvement in their symptoms, three patients (20%) much improvement and two patients (13%) minimal improvement. None of the patients experienced worsening of their symptoms. There was a statistically significant change in overall 15D score at 1 month (p < 0.001), 6 months (p = 0.001) and 12 months (p = 0.018), when the results were compared to baseline values. Median B&B score also improved significantly and decreased from a baseline value of 8 (4-12) to 4.5 (0-6), p = 0.002.
CONCLUSIONS
Based on the preliminary findings of our study, SNM might be a promising treatment of CPP in endometriosis patients.
Topics: Humans; Female; Endometriosis; Prospective Studies; Quality of Life; Pilot Projects; Pelvic Pain; Treatment Outcome; Electric Stimulation Therapy; Chronic Pain
PubMed: 37814355
DOI: 10.1111/aogs.14690 -
Technical Innovations & Patient Support... Sep 2023Liver stereotactic body radiotherapy (SBRT) is increasingly being used to treat tumours. The purpose of this study was to compare the differences in patient positioning...
INTRODUCTION
Liver stereotactic body radiotherapy (SBRT) is increasingly being used to treat tumours. The purpose of this study was to compare the differences in patient positioning when using implanted fiducials as surrogates compared to alternative methods based on liver contour or bone registration.
MATERIAL AND METHODS
Eighteen patients treated with SBRT who underwent a fiducial placement procedure were included. Fiducial guidance was our gold standard to guide treatment in this study. After recording the displacements, when fusing the planning CT and CBCT performed in the treatment unit using fiducials, liver contour and bone reference, the differences between fiducials and liver contour and bone reference were calculated. Data from 88 CBCT were analyzed. The correlation between the displacements found with fiducials and those performed based on the liver contour and the nearest bone structure as references was determined. The mean, median, variance, range and standard deviation of the displacements with each of the fusion methods were obtained. μ, Ʃ, and σ values and margins were obtained.
RESULTS
Lateral displacements of less than 3 mm with respect to the gold standard in 92% vs. 62.5% of cases using liver contour and bone references, respectively, with 93.2% vs. 65.9% in the AP axis and SI movement in 69.3% vs. 51.1%. The errors μ, σ and Ʃ of the fusions with hepatic contour and bone reference in SI were 0.26 mm, 4 mm and 3 mm, and 0.8 mm, 5 mm and 3 mm respectively.
CONCLUSION
Our study showed that displacements were smaller with the use of hepatic contour compared to bone reference and comparable to those obtained with the use of fiducials in the lateral, AP and SI motion axes. This would justify that hepatic contouring can be a guide in the treatment of patients in the absence of fiducials.
PubMed: 37744524
DOI: 10.1016/j.tipsro.2023.100215 -
Hernia : the Journal of Hernias and... Feb 2024In this long-term follow-up of a prospective, randomized, and multicenter study, we compare the results of a group receiving laparoscopic incisional ventral hernia...
PURPOSE
In this long-term follow-up of a prospective, randomized, and multicenter study, we compare the results of a group receiving laparoscopic incisional ventral hernia repair using intraperitoneal onlay mesh (LG) to a group receiving a hybrid hernia repair where open closure of fascial defect was added to intraperitoneal mesh placement (HG).
METHODS
Originally, 193 patients with 2-7 cm incisional hernias were randomly assigned to either the LG or HG during the 30-month recruitment period in 2012 to 2015. Long-term follow-up was conducted 5-10 years after surgery to evaluate hernia recurrence rate and quality of life (QoL).
RESULTS
In all, 65 patients in the LG and 60 in the HG completed the long-term follow-up with a median follow-up period of 87 months. Recurrent hernia was detected in 11 of 65 patients (16.9%) in the LG and 10 of 60 patients (16.7%) in the HG (p > 0.9). Kaplan-Meier analysis demonstrated a recurrence rate approaching 20% in both groups, with similar curves. Three patients in the LG (4.6% and five patients in the HG (8.1%) had undergone re-operation due to recurrence (p = 0.48). There was no difference in patient-reported QoL measured using the SF-36 questionnaire. Mean pain scores were similar between groups, mean numeric rating scale (NRS) 0 to 10 being 1.1 in the LG and 0.7 in the HG (p = 0.43).
CONCLUSION
Fascial closure did not reduce hernia recurrence rate in this study population, even though it has been shown to be beneficial and recommended in surgery guidelines. In the long term, recurrence rate for both groups is similar.
Topics: Humans; Follow-Up Studies; Hernia, Ventral; Herniorrhaphy; Incisional Hernia; Laparoscopy; Prospective Studies; Quality of Life; Recurrence; Surgical Mesh; Randomized Controlled Trials as Topic; Multicenter Studies as Topic
PubMed: 37594636
DOI: 10.1007/s10029-023-02849-1 -
Plants (Basel, Switzerland) Jul 2023The environment is the main factor affecting variations in phytochemicals and antioxidant activity in rice. The objective of this study was to evaluate the stability of...
The environment is the main factor affecting variations in phytochemicals and antioxidant activity in rice. The objective of this study was to evaluate the stability of grain yield, phytochemicals and antioxidant capacity of six rice genotypes. Six rice genotypes were evaluated in a randomized complete block design with three replicates at three locations in Trat, Bangkok and Sakon Nakhon provinces in July-October 2019. Data on grain yield, yield components, total phenolic content, ferulic acid and antioxidant capacity were recorded. Grain yield was highest for crops grown in Bangkok, whereas antioxidant activity was highest for crops grown in Bangkok and Sakon Nakhon. Hom Nang Nual 1 and Mali Nil Boran had the highest grain yield. Riceberry had the highest grain yield in Trat; it also had high levels of total phenolic compounds, ferulic acid and antioxidant activity. Mali Nil Boran, Mali Nil Surin and Riceberry had the most stable total phenolic content, ferulic acid and antioxidant activity, respectively. Information on the levels and variability of phytochemicals in rice enables the selection of genotypes with high and stabile phytochemicals for production and rice breeding.
PubMed: 37570941
DOI: 10.3390/plants12152787 -
Cancer Diagnosis & Prognosis 2023The optimal imaging test for delineation of the gross tumor volume (GTV) in hepatocellular carcinoma has not been defined. The hypothesis is that magnetic resonance...
BACKGROUND/AIM
The optimal imaging test for delineation of the gross tumor volume (GTV) in hepatocellular carcinoma has not been defined. The hypothesis is that magnetic resonance imaging (MRI) allows for better visualization of the extent of tumor and will optimize the accuracy of tumor delineation for liver stereotactic radiotherapy compared with computed tomography (CT) only. We evaluated the interobserver agreement in GTV of hepatocellular carcinoma in a multicenter panel and compared MRI and CT in GTV delineation.
MATERIALS AND METHODS
After the institutional review boards approved the study, we analyzed anonymous CT and MRI obtained from five patients with hepatocellular carcinoma. Eight radiation oncologists at our center used CT and MRI to delineate five GTVs of liver tumors. In both CT and MRI, the GTV volumes were compared.
RESULTS
The median GTV volume on MRI was 2.4 cm (range=0.59-15.6 cm) compared to 3.5 cm (range=0.52-24.9 cm) on CT (p=0.36). The GTV volume as defined on MRI was larger or at least as large as the GTV volume on CT in two cases. Variance and standard deviation between observers in CT and MRI were minor (6 vs. 7.87 cm, and 2.5 vs. 2.8 cm respectively).
CONCLUSION
In cases with well-defined tumors, CT is easier and reproducible. In cases with no defined tumor in CT, other tools are needed and MRI can be complementary. The interobserver variability in target delineation of hepatocellular carcinoma in this study is noteworthy.
PubMed: 37405211
DOI: 10.21873/cdp.10236 -
International Journal of Molecular... Apr 2023Colorectal cancer (CRC) is one of the most common cancers in Western countries and remains the second most common cause of cancer death worldwide. Many studies show the... (Review)
Review
Colorectal cancer (CRC) is one of the most common cancers in Western countries and remains the second most common cause of cancer death worldwide. Many studies show the importance of diet and lifestyle in the incidence of CRC, as well as in CRC prevention. However, this review summarizes those studies that analyze the impact of nutrition on tumor microenvironment modulation and cancer progression. We review the available information about the effects of specific nutrients on cancer cell progression and on the different cells within the tumor microenvironment. Diet and nutritional status in the clinical management of colorectal cancer patients are also analyzed. Finally, future perspectives and challenges are discussed, with a view to improving CRC treatments by employing nutritional approaches. These promise great benefits and will eventually improve CRC patients' survival.
Topics: Humans; Tumor Microenvironment; Colorectal Neoplasms; Diet; Life Style
PubMed: 37108477
DOI: 10.3390/ijms24087317 -
JAMA Surgery Jun 2023Both elective sigmoid resection and conservative treatment are options for patients with recurrent, complicated, or persistent painful diverticulitis; understanding...
Quality-of-Life and Recurrence Outcomes Following Laparoscopic Elective Sigmoid Resection vs Conservative Treatment Following Diverticulitis: Prespecified 2-Year Analysis of the LASER Randomized Clinical Trial.
IMPORTANCE
Both elective sigmoid resection and conservative treatment are options for patients with recurrent, complicated, or persistent painful diverticulitis; understanding outcomes following each can help inform decision-making.
OBJECTIVE
To compare outcomes of elective sigmoid resection and conservative treatment for patients with recurrent, complicated, or persistent painful diverticulitis at 2-year follow-up.
DESIGN, SETTING, AND PARTICIPANTS
This multicenter parallel open-label individually randomized clinical trial comparing elective sigmoid resection to conservative treatment in patients with recurrent, complicated, or persistent painful diverticulitis was carried out in 5 Finnish hospitals between September 2014 and October 2018. Follow-up up to 2 years is reported. Of 85 patients randomized and included, 75 and 70 were available for QOL outcomes at 1 year and 2 years, respectively, and 79 and 78 were available for the recurrence outcome at 1 year and 2 years, respectively. The present analysis was conducted from September 2015 to June 2022.
INTERVENTIONS
Laparoscopic elective sigmoid resection vs conservative treatment (patient education and fiber supplementation).
MAIN OUTCOMES AND MEASURES
Prespecified secondary outcomes included Gastrointestinal Quality of Life Index (GIQLI) score, complications, and recurrences within 2 years.
RESULTS
Ninety patients (28 male [31%]; mean [SD] age, 54.11 [11.9] years and 62 female [69%]; mean [SD] age, 57.13 [7.6] years) were randomized either to elective sigmoid resection or conservative treatment. After exclusions, 41 patients in the surgery group and 44 in the conservative group were included in the intention-to-treat analyses. Eight patients (18%) in the conservative treatment group underwent sigmoid resection within 2 years. The mean GIQLI score at 1 year was 9.51 points higher in the surgery group compared to the conservative group (mean [SD], 118.54 [17.95] vs 109.03 [19.32]; 95% CI, 0.83-18.18; P = .03), while the mean GIQLI score at 2 years was similar between the groups. Within 2 years, 25 of 41 patients in the conservative group (61%) had recurrent diverticulitis compared to 4 of 37 patients in the surgery group (11%). Four of 41 patients in the surgery group (10%) and 2 of 44 in the conservative group (5%) had major postoperative complications within 2 years. In per-protocol analyses, the mean (SD) GIQLI score was higher in the surgery group compared to the conservative treatment group by 11.27 points at 12 months (119.42 [17.98] vs 108.15 [19.28]; 95% CI, 2.24-20.29; P = .02) and 10.43 points at 24 months (117.24 [15.51] vs 106.82 [18.94]; 95% CI, 1.52-19.33; P = .02).
CONCLUSIONS AND RELEVANCE
In this randomized clinical trial, elective sigmoid resection was effective in preventing recurrent diverticulitis and improved quality of life over conservative treatment within 2 years.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02174926.
Topics: Humans; Male; Female; Middle Aged; Quality of Life; Conservative Treatment; Treatment Outcome; Neoplasm Recurrence, Local; Diverticulitis; Laparoscopy
PubMed: 37074706
DOI: 10.1001/jamasurg.2023.0466