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Journal of Cancer Research and... Jun 2024Pancreatic ductal adenocarcinoma is the fourth leading cause of cancer-related deaths globally, with a five-year survival rate of only 5%.
INTRODUCTION
Pancreatic ductal adenocarcinoma is the fourth leading cause of cancer-related deaths globally, with a five-year survival rate of only 5%.
OBJECTIVES
Pancreatic ductal adenocarcinoma is often fatal because of the lack of specific early symptoms and effective early screening tools. Therefore, 80%-85% of patients are usually diagnosed in the advanced stages. This study aimed to investigate the analgesic effect of transcutaneous electrical acupoint stimulation in patients with advanced pancreatic cancer.
METHODS
Eighty patients with advanced pancreatic cancer were recruited from the Integrative Medicine Department of our hospital between June 2017 and October 2018 and randomly divided into the experimental group (n = 40) and the control group (n = 40). The experimental group received transcutaneous electrical acupoint stimulation combined with analgesic medication for 3 consecutive days, while the control group received only analgesic medication. The pain scores of the two groups before and after intervention were compared.
RESULTS
The mean pain severity score was significantly lower in the experimental group than in the control group on day 1 (P < 0.001), day 2 (P < 0.001), day 3 (P = 0.005), and day 4 (P = 0.043).
CONCLUSION
Transcutaneous electrical acupoint stimulation therapy effectively alleviates the pain of patients with advanced pancreatic cancer with a high degree of safety and minimal adverse effects, and is worthy of clinical application.
PubMed: 38935575
DOI: 10.4103/jcrt.jcrt_2172_23 -
Clinical and Translational Medicine Jul 2024Hepatitis B virus (HBV) infection playsa significant role in the etiology and progression of liver-relatedpathologies, encompassing chronic hepatitis, fibrosis,... (Review)
Review
Hepatitis B virus (HBV) infection playsa significant role in the etiology and progression of liver-relatedpathologies, encompassing chronic hepatitis, fibrosis, cirrhosis, and eventual hepatocellularcarcinoma (HCC). Notably, HBV infection stands as the primary etiologicalfactor driving the development of HCC. Given the significant contribution ofHBV infection to liver diseases, a comprehensive understanding of immunedynamics in the liver microenvironment, spanning chronic HBV infection,fibrosis, cirrhosis, and HCC, is essential. In this review, we focused on thefunctional alterations of CD8 T cells within the pathogenic livermicroenvironment from HBV infection to HCC. We thoroughly reviewed the roles ofhypoxia, acidic pH, metabolic reprogramming, amino acid deficiency, inhibitory checkpointmolecules, immunosuppressive cytokines, and the gut-liver communication in shapingthe dysfunction of CD8 T cells in the liver microenvironment. Thesefactors significantly impact the clinical prognosis. Furthermore, we comprehensivelyreviewed CD8 T cell-based therapy strategies for liver diseases,encompassing HBV infection, fibrosis, cirrhosis, and HCC. Strategies includeimmune checkpoint blockades, metabolic T-cell targeting therapy, therapeuticT-cell vaccination, and adoptive transfer of genetically engineered CD8 T cells, along with the combined usage of programmed cell death protein-1/programmeddeath ligand-1 (PD-1/PD-L1) inhibitors with mitochondria-targeted antioxidants.Given that targeting CD8 T cells at various stages of hepatitis Bvirus-induced hepatocellular carcinoma (HBV + HCC) shows promise, we reviewedthe ongoing need for research to elucidate the complex interplay between CD8 T cells and the liver microenvironment in the progression of HBV infection toHCC. We also discussed personalized treatment regimens, combining therapeuticstrategies and harnessing gut microbiota modulation, which holds potential forenhanced clinical benefits. In conclusion, this review delves into the immunedynamics of CD8 T cells, microenvironment changes, and therapeuticstrategies within the liver during chronic HBV infection, HCC progression, andrelated liver diseases.
Topics: Humans; CD8-Positive T-Lymphocytes; Hepatitis B virus; Hepatitis B, Chronic; Carcinoma, Hepatocellular; Liver Neoplasms; Liver Diseases
PubMed: 38935536
DOI: 10.1002/ctm2.1731 -
Langenbeck's Archives of Surgery Jun 2024Perioperative chemotherapy combined with surgical resection represent the gold standard in the treatment of locally advanced gastric cancer. The Mandard tumor regression...
PURPOSE
Perioperative chemotherapy combined with surgical resection represent the gold standard in the treatment of locally advanced gastric cancer. The Mandard tumor regression score (TRG) is widely used to evaluate pathological response to neoadjuvant treatment. The aim of this study was to assess the prognostic value of TRG in terms of overall survival (OS) and disease-free (DFS).
METHODS
Retrospective analysis of all consecutive patients who underwent oncological gastrectomy after neoadjuvant chemotherapy from January 2007 to December 2019 for gastric adenocarcinoma was performed. Based on their TRG status they were categorized into two groups: good responders (TRG 1-2) and poor responders (TRG 3-5). Subsequent multivariable analyses were conducted.
RESULTS
Seventy-four patients were included, whereby 15 (20.3%) were TRG 1-2. Neoadjuvant regimens for TRG 1-2 vs. TRG 3-5 were similar: MAGIC (53% vs. 39%), FLOT (40% vs. 36%), FOLFOX (7% vs. 15%, p = 0.462). Histologic types according to Lauren classification for TRG 1-2 vs. TRG 3-5 were: 13% vs. 29% intestinal, 53% vs. 44% diffuse and 34% vs. 27% indeterminate (p = 0.326). TRG 1-2 group exhibited significantly less advanced ypT (46% vs. 10%, p = 0.001) and ypN stages (66% vs. 37%, p = 0.008), alongside a diminished recurrence rate (20% vs. 42%, p = 0.111). The 3-year DFS was significantly better in this group (81% vs. 47%, p = 0.041) whereas the disparity in three-year OS (92% vs. 55%, p = 0.054) did not attain statistical significance.
CONCLUSIONS
TRG 1-2 was associated with less advanced ypT and ypN stage and better DFS compared to TRG 3-5 patients, without a significant impact on OS.
Topics: Humans; Stomach Neoplasms; Gastrectomy; Male; Female; Retrospective Studies; Middle Aged; Aged; Prognosis; Neoadjuvant Therapy; Adenocarcinoma; Neoplasm Grading; Adult; Neoplasm Staging; Disease-Free Survival; Chemotherapy, Adjuvant; Survival Rate; Treatment Outcome
PubMed: 38935163
DOI: 10.1007/s00423-024-03388-8 -
Hepatology Communications Jul 2024Selective internal radiation therapy (SIRT) is recommended as a downstaging (DS) strategy for solitary unresectable HCC <8 cm. The aim of this study was to report the... (Observational Study)
Observational Study
BACKGROUND
Selective internal radiation therapy (SIRT) is recommended as a downstaging (DS) strategy for solitary unresectable HCC <8 cm. The aim of this study was to report the results of acquired experience in a tertiary center for all unresectable HCCs.
METHODS
We conducted a retrospective, observational study using data collected from consecutive patients undergoing SIRT between October 2013 and June 2020. DS was considered achieved when a curative treatment could be proposed 6 months after SIRT.
RESULTS
One hundred twenty-seven patients were included (male = 90%, 64 ± 11 y), of whom 112 (n = 88%) had cirrhosis. HCC was classified as BCLC stage C in 64 patients (50%), with a median diameter of 61 mm, an infiltrative pattern in 51 patients (40%), and portal vein invasion in 62 (49%) patients. Fifty patients (39%) achieved DS 6 months following SIRT, with 29 of them (23%) undergoing curative treatment in a median time of 4.3 months: 17 (13%) were transplanted, 11 (85%) had liver resection, and 1 patient had a radiofrequency ablation. The median overall survival of patients with or without DS was 51 versus 10 months, respectively (p < 0.001). In patients who achieved DS, progression-free survival was higher in patients who underwent surgery: 47 versus 11 months (p < 0.001). Four variables were independently associated with DS: age (OR: 0.96, 95% CI: [0.92, 0.99]; p = 0.032), baseline α-fetoprotein (OR: 1.00, 95% CI: [1.00, 1.00]; p = 0.034), HCC distribution (OR: 0.3, 95% CI: [0.11, 0.75]; p = 0.012), and ALBI grade (OR: 0.34. 95% CI: [0.14, 0.80]; p = 0.014).
CONCLUSIONS
These results suggest that SIRT in patients with unresectable HCC could be an effective treatment: DS was achieved for around 39% of the patients and more than half of these then underwent curative treatment.
Topics: Humans; Liver Neoplasms; Male; Carcinoma, Hepatocellular; Female; Middle Aged; Retrospective Studies; Aged; Neoplasm Staging; Brachytherapy; Yttrium Radioisotopes; Treatment Outcome
PubMed: 38934702
DOI: 10.1097/HC9.0000000000000475 -
Archivio Italiano Di Urologia,... Jun 2024Breast cancer (BrC) is the most frequently diagnosed malignancy in woman and most BrC related deaths are due to metastasis. BrC frequently metastasizes to the lymph...
Breast cancer (BrC) is the most frequently diagnosed malignancy in woman and most BrC related deaths are due to metastasis. BrC frequently metastasizes to the lymph nodes, liver, lung, bone and brain while the urinary bladder is considered as an unusual site for breast metastasis. We report a case of bladder metastasis identified in a patient with past BrC history, presenting with hematuria, low urinary tract symptoms, and hydronephrosis.
Topics: Humans; Female; Urinary Bladder Neoplasms; Breast Neoplasms; Linitis Plastica; Middle Aged; Hematuria
PubMed: 38934524
DOI: 10.4081/aiua.2024.12483 -
Frontiers in Genetics 2024Cervical cancer, a prevalent gynecological malignant tumor, poses a significant threat to women's health and lives. Immune checkpoint inhibitor (ICI) therapy has emerged...
BACKGROUND AND AIMS
Cervical cancer, a prevalent gynecological malignant tumor, poses a significant threat to women's health and lives. Immune checkpoint inhibitor (ICI) therapy has emerged as a promising avenue for treating cervical cancer. For patients with persistent or recurrent metastatic cervical cancer, If the sequence of dead receptor ligand-1 (PD-L1) is positive, ICI show significant clinical efficacy. PD-L1 expression serves as a valuable biomarker for assessing ICI therapeutic efficacy. However, the complex tumor immune microenvironment (TIME), encompassing immune cell composition and tumor-infiltrating lymphocyte (TIL) status, also exerts a profound influence on tumor immunity and prognosis. Given the remarkable strides made by ICI treatments in improving the survival rates of cervical cancer patients, it becomes essential to identify a comprehensive biomarker that integrates various TIME aspects to enhance the effectiveness of ICI treatment. Therefore, the quest for biomarkers linked to multiple facets of TIME in cervical cancer is a vital pursuit.
METHODS
In this study, we have developed an Immune-Associated Gene Prognostic Index (IRGPI) with remarkable prognostic value specifically for cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC). The Cancer Genome Atlas CESC dataset ( = 305) was meticulously analyzed to pinpoint key immune-related genes via weighted gene co-expression network analysis and differential gene expression assays. Subsequently, we employed Cox regression analysis to construct the IRGPI. Furthermore, the composition of immune cells and TIL status were examined using CIBERSORT and TIDE. Tumor expression of Epigen, LCN10, and P73 were determined with immunohistochemistry.
RESULTS
The resulting IRGPI, composed of EPGN, LCN10, and TP73 genes, displayed a strong negative correlation with patient survival. The discovery was validated with a patient cohort from our hospital. The IRGPI not only predicts the composition of immune cell subtypes such as Macrophages M1, NK cells, Mast cells, Plasma cells, Neutrophils, Dendritic cells, T cells CD8, and T cells CD4 within CESC, but also indicates TIL exclusion, dysfunction, and PD-1 and PD-L1 expression. Therefore, the IRGPI emerges as a promising biomarker not only for prognostic assessment but also for characterizing multiple immune features in CESC. Additionally, our results underscored the significant associations between the IRGPI and immune cell composition, TIL exclusion, and dysfunction, along with PD-1 and PD-L1 expression in the TIME.
CONCLUSION
Consequently, the IRGPI stands out as a biomarker intimately connected to both the survival and TIME status of CESC patients, offering potential insights into immunotherapy strategies for CESC.
PubMed: 38933923
DOI: 10.3389/fgene.2024.1340569 -
JGH Open : An Open Access Journal of... Jun 2024Atrophic gastritis (AG) and gastric intestinal metaplasia (GIM) are early changes in the stepwise progression to gastric adenocarcinoma. There is heterogeneity in...
BACKGROUND AND AIM
Atrophic gastritis (AG) and gastric intestinal metaplasia (GIM) are early changes in the stepwise progression to gastric adenocarcinoma. There is heterogeneity in international guidelines regarding the endoscopic diagnosis and surveillance of AG and GIM. This study aims to determine the prevalence of GIM in an Australian center and assess the approach of Australian endoscopists for these two conditions.
METHODS
We conducted a single-center retrospective study of adult patients between January 2015 and December 2020 diagnosed with GIM on gastric biopsy following upper gastric endoscopy. A web-based, 25-question, investigator-designed, multiple-choice survey was distributed among all registered endoscopists in Australia.
RESULTS
The overall prevalence of GIM within a single Australian center was 11.7% over 5 years. Of the 1026 patients identified, only 58.7% underwent mapping biopsies using the modified Sydney protocol. Among the cohort, 1.6% had low-grade dysplasia, 0.9% had high-grade dysplasia, and 1.8% had malignancy on initial gastroscopy. Two hundred and sixty-seven (7.2%) endoscopists completed the survey, 44.2% indicated they would perform mapping for all patients, and 36% only for high-risk patients. Only 1.5% ( = 4) of respondents were able to correctly identify all six endoscopic photos of GIM/AG.
CONCLUSION
This study demonstrates that in a large tertiary center, GIM is a prevalent endoscopic finding, but the associated rates of dysplasia and cancer were low. Additionally, among a small proportion of surveyed Australian endoscopists, there is notable variability in the endoscopic approach for AG and GIM and significant knowledge gaps. More training is required to increase the recognition of GIM and compliance with histological mapping.
PubMed: 38933895
DOI: 10.1002/jgh3.13115 -
Oncology Letters Aug 2024Pancreatic ductal adenocarcinoma (PDAC) is associated with a poor prognosis, and it has a recurrence rate of >70%, even in resectable cases. The treatment strategy for...
Pancreatic ductal adenocarcinoma (PDAC) is associated with a poor prognosis, and it has a recurrence rate of >70%, even in resectable cases. The treatment strategy for recurrent PDAC involves systemic chemotherapy, with gemcitabine (GEM) monotherapy historically serving as the standard of care. The present study describes the case of a patient with PDAC and postoperative liver metastases that maintained clinical complete remission (cCR) for >7 years following GEM monotherapy. A 63-year-old woman with upper abdominal pain was diagnosed with resectable PDAC and underwent pancreaticoduodenectomy. The patient was treated with GEM + S-1 as adjuvant chemotherapy for 6 months. Multiple liver metastases were detected 15 months post-operation and the patient was administered GEM alone. After 12 cycles, computed tomography showed cCR and GEM monotherapy was discontinued after 15 cycles. The patient has had no signs or symptoms of recurrence >7 years after the first recurrence. In addition, the present study analyzed PDAC resection specimens from four patients, including this case, to determine the expression levels of hENT1 protein in the tumor tissues. hENT1 is a transmembrane protein that acts as a nucleoside transporter and is a major mediator of GEM uptake into human cells. In the present case, hENT1 staining exhibited low frequency and weak positivity in the central region, whereas a strong positive reaction was observed in nearly all cell membranes at the invasive front of the cancer. The location, intensity, and frequency of hENT1 staining varied among cases. In conclusion, the efficacy of GEM may be predicted prior to treatment by evaluating hENT1 expression.
PubMed: 38933809
DOI: 10.3892/ol.2024.14503 -
Frontiers in Surgery 2024Advancements in surgical techniques have improved outcomes in patients undergoing pancreatic surgery. To date there have been no meta-analyses comparing robotic and...
BACKGROUND
Advancements in surgical techniques have improved outcomes in patients undergoing pancreatic surgery. To date there have been no meta-analyses comparing robotic and laparoscopic approaches for distal pancreatectomies (DP) in patients with pancreatic adenocarcinoma (PDAC). This systematic review and network meta-analysis aims to explore the oncological outcomes of laparoscopic distal pancreatectomy (LDP), robotic distal pancreatectomy (RDP) and open distal pancreatectomy (ODP).
METHODS
A systematic search was conducted for studies reporting laparoscopic, robotic or open surgery for DP. Frequentist network meta-analysis of oncological outcomes (overall survival, resection margins, tumor recurrence, examined lymph nodes, administration of adjuvant therapy) were performed.
RESULTS
Fifteen studies totalling 9,301 patients were included in the network meta-analysis. 1,946, 605 and 6,750 patients underwent LDP, RDP and ODP respectively. LDP (HR: 0.761, 95% CI: 0.642-0.901, = 0.002) and RDP (HR: 0.757, 95% CI: 0.617-0.928, = 0.008) were associated with overall survival (OS) benefit when compared to ODP. LDP (HR: 1.00, 95% CI: 0.793-1.27, = 0.968) was not associated with OS benefit when compared to RDP. There were no significant differences between LDP, RDP and ODP for resection margins, tumor recurrence, examined lymph nodes and administration of adjuvant therapy.
CONCLUSION
This study highlights the longer OS in both LDP and RDP when compared to ODP for patients with PDAC.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/, PROSPERO (CRD42022336417).
PubMed: 38933652
DOI: 10.3389/fsurg.2024.1369169 -
F1000Research 2023The risk of recurrence after nephrectomy for primary clear cell renal cell carcinoma (ccRCC) is estimated in daily practice solely based on clinical criteria. The aim of...
BACKGROUND
The risk of recurrence after nephrectomy for primary clear cell renal cell carcinoma (ccRCC) is estimated in daily practice solely based on clinical criteria. The aim of this study was to assess the prognostic relevance of common somatic mutations with respect to tumor aggressiveness and outcomes of ccRCC patients after definitive treatment.
METHODS
Primary tumors from 37 patients with ccRCC who underwent radical nephrectomy were analyzed for presence of somatic mutations using a 15-gene targeted next-generation sequencing (NGS) panel. Associations to histopathologic characteristics and outcomes were investigated in the study cohort (n=37) and validated in The Cancer Genome Atlas (TCGA) ccRCC cohort (n=451).
RESULTS
was the most frequently mutated gene (51%), followed by (27%), (13%), (13%), (5%), (5%), (5%), and (3%). One-third of patients did not have any somatic mutations within the 15-gene panel. The vast majority of tumors harboring no mutations at all or VHL-only mutations (51%) were more frequently of smaller size (pT1-2) and earlier stage (I/II), whereas presence of any other gene mutations in various combinations with or without was enriched in larger (pT3) and higher stage tumors (III) (p=0.02). No recurrences were noted in patients with unmutated tumors or -only mutations as opposed to three relapses in patients with non- somatic mutations (p=0.06). Presence of somatic mutations in , or genes in 451 TCGA ccRCC patients was associated with a significantly shorter disease-free survival (DFS) compared to those with unaltered tumors (q=0.01).
CONCLUSIONS
Preliminary findings from this ongoing study support the prognostic value of non- mutations including , and in primary ccRCC tumors as surrogates of earlier recurrence and potential selection for adjuvant immune checkpoint inhibition.
Topics: Humans; Carcinoma, Renal Cell; Male; Female; Kidney Neoplasms; Middle Aged; Mutation; Aged; Immune Checkpoint Inhibitors; Ubiquitin Thiolesterase; Neoplasm Recurrence, Local; Tumor Suppressor Proteins; Ataxia Telangiectasia Mutated Proteins; Von Hippel-Lindau Tumor Suppressor Protein; Prognosis; Histone-Lysine N-Methyltransferase; Adult; Transcription Factors; Aged, 80 and over; Nuclear Proteins; High-Throughput Nucleotide Sequencing; DNA-Binding Proteins; Histone Demethylases
PubMed: 38933491
DOI: 10.12688/f1000research.136087.2