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International Journal of Molecular... May 2024Metformin, a medication known for its anti-glycemic properties, also demonstrates potent immune system activation. In our study, using a 4T1 breast cancer model in...
Metformin, a medication known for its anti-glycemic properties, also demonstrates potent immune system activation. In our study, using a 4T1 breast cancer model in BALB/C WT mice, we examined metformin's impact on the functional phenotype of multiple immune cells, with a specific emphasis on natural killer T (NKT) cells due to their understudied role in this context. Metformin administration delayed the appearance and growth of carcinoma. Furthermore, metformin increased the percentage of IFN-γ NKT cells, and enhanced CD107a expression, as measured by MFI, while decreasing PD-1, FoxP3, and IL-10 NKT cells in spleens of metformin-treated mice. In primary tumors, metformin increased the percentage of NKp46 NKT cells and increased FasL expression, while lowering the percentages of FoxP3, PD-1, and IL-10-producing NKT cells and KLRG1 expression. Activation markers increased, and immunosuppressive markers declined in T cells from both the spleen and tumors. Furthermore, metformin decreased IL-10 and FoxP3 Tregs, along with Gr-1 myeloid-derived suppressor cells (MDSCs) in spleens, and in tumor tissue, it decreased IL-10 and FoxP3 Tregs, Gr-1, NF-κB, and iNOS MDSCs, and iNOS dendritic cells (DCs), while increasing the DCs quantity. Additionally, increased expression levels of MIP1a, STAT4, and NFAT in splenocytes were found. These comprehensive findings illustrate metformin's broad immunomodulatory impact across a variety of immune cells, including stimulating NKT cells and T cells, while inhibiting Tregs and MDSCs. This dynamic modulation may potentiate its use in cancer immunotherapy, highlighting its potential to modulate the tumor microenvironment across a spectrum of immune cell types.
Topics: Metformin; Animals; Female; Mice; Breast Neoplasms; Mice, Inbred BALB C; Cell Line, Tumor; Myeloid-Derived Suppressor Cells; Natural Killer T-Cells; T-Lymphocytes, Regulatory; Immunomodulating Agents
PubMed: 38892058
DOI: 10.3390/ijms25115869 -
Animals : An Open Access Journal From... Jun 2024Myelolipoma is a benign, typically inert neoplasm of uncertain aetiology that is rarely reported in cats. Although commonly asymptomatic, in some cases, myelolipomas can...
Myelolipoma is a benign, typically inert neoplasm of uncertain aetiology that is rarely reported in cats. Although commonly asymptomatic, in some cases, myelolipomas can cause abdominal discomfort or present with rupture and haemorrhage. Here, we describe a rare case of a splenic myelolipoma in a Domestic Long Hair cat in which, after extensive diagnostic investigations, clinical signs of hyporexia and weight loss were attributable to the presence of an intra-abdominal mass. The patient was treated by splenectomy and unexpectedly died during the post-operative period. Although splenectomy appears to be a sensible intervention in symptomatic patients, the optimal management of splenic myelolipomas in cats remains unknown. The risk-benefit ratio of surgical management needs to be carefully considered, and therapeutic intervention should be tailored individually to each patient.
PubMed: 38891746
DOI: 10.3390/ani14111700 -
BMC Medical Imaging Jun 2024Abdominal CT scans are vital for diagnosing abdominal diseases but have limitations in tissue analysis and soft tissue detection. Dual-energy CT (DECT) can improve these...
BACKGROUND
Abdominal CT scans are vital for diagnosing abdominal diseases but have limitations in tissue analysis and soft tissue detection. Dual-energy CT (DECT) can improve these issues by offering low keV virtual monoenergetic images (VMI), enhancing lesion detection and tissue characterization. However, its cost limits widespread use.
PURPOSE
To develop a model that converts conventional images (CI) into generative virtual monoenergetic images at 40 keV (Gen-VMI) of the upper abdomen CT scan.
METHODS
Totally 444 patients who underwent upper abdominal spectral contrast-enhanced CT were enrolled and assigned to the training and validation datasets (7:3). Then, 40-keV portal-vein virtual monoenergetic (VMI) and CI, generated from spectral CT scans, served as target and source images. These images were employed to build and train a CI-VMI model. Indexes such as Mean Absolute Error (MAE), Peak Signal-to-Noise Ratio (PSNR), and Structural Similarity (SSIM) were utilized to determine the best generator mode. An additional 198 cases were divided into three test groups, including Group 1 (58 cases with visible abnormalities), Group 2 (40 cases with hepatocellular carcinoma [HCC]) and Group 3 (100 cases from a publicly available HCC dataset). Both subjective and objective evaluations were performed. Comparisons, correlation analyses and Bland-Altman plot analyses were performed.
RESULTS
The 192nd iteration produced the best generator mode (lower MAE and highest PSNR and SSIM). In the Test groups (1 and 2), both VMI and Gen-VMI significantly improved CT values, as well as SNR and CNR, for all organs compared to CI. Significant positive correlations for objective indexes were found between Gen-VMI and VMI in various organs and lesions. Bland-Altman analysis showed that the differences between both imaging types mostly fell within the 95% confidence interval. Pearson's and Spearman's correlation coefficients for objective scores between Gen-VMI and VMI in Groups 1 and 2 ranged from 0.645 to 0.980. In Group 3, Gen-VMI yielded significantly higher CT values for HCC (220.5HU vs. 109.1HU) and liver (220.0HU vs. 112.8HU) compared to CI (p < 0.01). The CNR for HCC/liver was also significantly higher in Gen-VMI (2.0 vs. 1.2) than in CI (p < 0.01). Additionally, Gen-VMI was subjectively evaluated to have a higher image quality compared to CI.
CONCLUSION
CI-VMI model can generate Gen-VMI from conventional CT scan, closely resembling VMI.
Topics: Humans; Tomography, X-Ray Computed; Female; Male; Middle Aged; Radiography, Abdominal; Aged; Adult; Radiographic Image Interpretation, Computer-Assisted; Liver Neoplasms; Signal-To-Noise Ratio; Radiography, Dual-Energy Scanned Projection; Carcinoma, Hepatocellular; Aged, 80 and over; Contrast Media
PubMed: 38890572
DOI: 10.1186/s12880-024-01331-3 -
Endoscopy Dec 2024
Topics: Humans; Stomach Neoplasms; Sentinel Lymph Node Biopsy; Male; Sentinel Lymph Node; Gastroscopy; Female; Aged
PubMed: 38889895
DOI: 10.1055/a-2342-0221 -
The Journal of International Medical... Jun 2024Pelvic masses frequently originate from the pelvic cavity and are often associated with uterine, ovarian, or intestinal disorders. This report describes the case of a... (Review)
Review
Pelvic masses frequently originate from the pelvic cavity and are often associated with uterine, ovarian, or intestinal disorders. This report describes the case of a patient with a pelvic mass diagnosed as a retroperitoneal dermoid cyst at our hospital. We analyzed this case and conducted a literature review, to mitigate the risk of misdiagnosis and enhance the treatment of retroperitoneal masses.
Topics: Humans; Female; Dermoid Cyst; Retroperitoneal Neoplasms; Uterine Neoplasms; Adenomyoma; Tomography, X-Ray Computed; Adult
PubMed: 38886867
DOI: 10.1177/03000605241255810 -
Trials Jun 2024Complete surgical removal of pancreatic ductal adenocarcinoma (PDAC) is central to all curative treatment approaches for this aggressive disease, yet this is only...
SCANPatient: study protocol for a multi-centre, batched, stepped wedge, comparative effectiveness, randomised clinical trial of synoptic reporting of computerised tomography (CT) scans assessing cancers of the pancreas.
BACKGROUND
Complete surgical removal of pancreatic ductal adenocarcinoma (PDAC) is central to all curative treatment approaches for this aggressive disease, yet this is only possible in patients technically amenable to resection. Hence, an accurate assessment of whether patients are suitable for surgery is of paramount importance. The SCANPatient trial aims to test whether implementing a structured synoptic radiological report results in increased institutional accuracy in defining surgical resectability of non-metastatic PDAC.
METHODS
SCANPatient is a batched, stepped wedge, comparative effectiveness, cluster randomised clinical trial. The trial will be conducted at 33 Australian hospitals all of which hold regular multi-disciplinary team meetings (MDMs) to discuss newly diagnosed patients with PDAC. Each site is required to manage a minimum of 20 patients per year (across all stages). Hospitals will be randomised to begin synoptic reporting within a batched, stepped wedge design. Initially all hospitals will continue to use their current reporting method; within each batch, after each 6-month period, a randomly selected group of hospitals will commence using the synoptic reports, until all hospitals are using synoptic reporting. Each hospital will provide data from patients who (i) are aged 18 or older; (ii) have suspected PDAC and have an abdominal CT scan, and (iii) are presented at a participating MDM. Non-metastatic patients will be documented as one of the following categories: (1) locally advanced and surgically unresectable; (2) borderline resectable; or (3) anatomically clearly resectable (Note: Metastatic disease is treated as a separate category). Data collection will last for 36 months in each batch, and a total of 2400 patients will be included.
DISCUSSION
Better classifying patients with non-metastatic PDAC as having tumours that are either clearly resectable, borderline or locally advanced and unresectable may improve patient outcomes by optimising care and treatment planning. The borderline resectable group are a small but important cohort in whom surgery with curative intent may be considered; however, inconsistencies with definitions and an understanding of resectability status means these patients are often incorrectly classified and hence overlooked for curative options.
TRIAL REGISTRATION
The SCANPatient trial was registered on 17th May 2023 in the Australian New Zealand Clinical Trials Registry (ANZCTR) (ACTRN12623000508673).
Topics: Humans; Pancreatic Neoplasms; Carcinoma, Pancreatic Ductal; Randomized Controlled Trials as Topic; Multicenter Studies as Topic; Comparative Effectiveness Research; Tomography, X-Ray Computed; Predictive Value of Tests; Australia; Pancreatectomy
PubMed: 38886755
DOI: 10.1186/s13063-024-08196-5 -
BMC Gastroenterology Jun 2024Transanal total mesorectal excision (taTME) has improved the laparoscopic dissection for rectal cancer in the narrow pelvis. Although taTME has more clinical benefits...
Transanal total mesorectal excision (taTME) has improved the laparoscopic dissection for rectal cancer in the narrow pelvis. Although taTME has more clinical benefits than laparoscopic surgery, such as a better view of the distal rectum and direct determination of distal resection margin, an intraoperative urethral injury could occur in excision ta-TME. This study aimed to determine the feasibility and efficacy of the ta-TME with IRIS U kit surgery. This retrospective study enrolled 10 rectal cancer patients who underwent a taTME with an IRIS U kit. The study endpoints were the safety of access (intra- or postoperative morbidity). The detectability of the IRIS U kit catheter was investigated by using a laparoscope-ICG fluorescence camera system. Their mean age was 71.4±6.4 (58-78) years; 80 were men, and 2 were women. The mean operative time was 534.6 ± 94.5 min. The coloanal anastomosis was performed in 80%, and 20% underwent abdominal peritoneal resection. Two patients encountered postoperative complications graded as Clavien-Dindo grade 2. The transanal approach with IRIS U kit assistance is feasible, safe for patients with lower rectal cancer, and may prevent intraoperative urethral injury.
Topics: Humans; Rectal Neoplasms; Male; Female; Aged; Middle Aged; Retrospective Studies; Urethra; Transanal Endoscopic Surgery; Feasibility Studies; Postoperative Complications; Operative Time; Proctectomy; Intraoperative Complications; Rectum; Anastomosis, Surgical; Laparoscopy
PubMed: 38886646
DOI: 10.1186/s12876-024-03279-8 -
The Oncologist Jun 2024Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare neoplasms with an increasing annual incidence and prevalence. Many are metastatic at presentation or...
BACKGROUND
Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare neoplasms with an increasing annual incidence and prevalence. Many are metastatic at presentation or recur following surgical resection and require systemic therapy, for which somatostatin analogs such as octreotide or lanreotide comprise typical first-line therapies. Nonetheless, treatment options remain limited. Epigenetic processes such as histone modifications have been implicated in malignant transformation and progression. In this study, we evaluated the anti-proliferative effects of a histone deacetylase (HDAC) inhibitor, entinostat, which was computationally predicted to show anti-cancer activity, as confirmed in in vitro and in vivo models of GEP-NETs.
METHODS
This was a phase II study to evaluate the efficacy and safety of entinostat in patients with relapsed or refractory abdominal NETs. The primary objective was to estimate the objective response rate to entinostat. Additionally, with each patient as his/her own control we estimated the rates of tumor growth prior to enrollment on study and while receiving entinostat. Patients received 5 mg entinostat weekly until disease progression or intolerable toxicity. The dose could be changed to 10 mg biweekly for patients who did not experience grade ≥ 2 treatment-related adverse events (AEs) in cycle 1, but was primarily administered at the starting 5 mg weekly dose.
RESULTS
The study enrolled only 5 patients due to early termination by the drug sponsor. The first patient that enrolled had advanced disease and died within days of enrollment before follow-up imaging due to a grade 5 AE unrelated to study treatment and was considered non-evaluable. Best RECIST response for the remaining 4 patients was stable disease (SD) with time on study of 154+, 243, 574, and 741 days. With each patient as his/her own control, rates of tumor growth on entinostat were markedly reduced with rates 20%, 33%, 54%, and 68% of the rates prior to enrollment on study. Toxicities possibly or definitely related to entinostat included grade 2/3 neutrophil count decrease [2/4 (50%)/ 2/4 (50%)], grade 3 hypophosphatemia [1/4, (25%)], grade 1/2 fatigue [1/4 (25%)/ 2/4 (50%)], and other self-limiting grade 1/2 AEs.
CONCLUSION
In the treatment of relapsed or refractory abdominal NETs, entinostat 5 mg weekly led to prolonged SD and reduced the rate of tumor growth by 32% to 80% with an acceptable safety profile (ClinicalTrials.gov Identifier: NCT03211988).
PubMed: 38886159
DOI: 10.1093/oncolo/oyae118 -
Journal of Investigative Medicine High... 2024Rectal signet ring cell carcinoma represents a rare subtype of colorectal adenocarcinoma known for its aggressive biological nature and poor prognosis. Although the...
Rectal signet ring cell carcinoma represents a rare subtype of colorectal adenocarcinoma known for its aggressive biological nature and poor prognosis. Although the co-occurrence of colorectal carcinoma with other tumors has been reported, the uncommon phenomenon of tumor-to-tumor metastasis, first described in 1930, remains rare. The most frequent donor neoplasms are lung or breast carcinomas, whereas cerebral meningiomas have been reported to be the most frequent recipient neoplasms. Here we report a case of a typical lipomatous tumor harboring metastatic signet ring cell rectal carcinoma. It is about a 42-year-old man diagnosed with rectal signet ring cell carcinoma and treated with concurrent radiotherapy and chemotherapy followed by an anterior resection and manual coloanal anastomosis with a temporary ileostomy. During the surgery, an abdominal wall lipoma was discovered and excised. A histopathological examination revealed infiltration of the fibro adipose tissue by a mucinous adenocarcinoma with a contingent of signet ring cells. The patient died 12 months after adjuvant chemotherapy due to peritoneal progression. To the best of our understanding, this represents the initial documented instance of tumor-to-tumor metastasis from rectal signet cell carcinoma to a conventional nonvascular lipoma. Consequently, even if one of these tumors appears clinically and radiologically benign, it is prudent to entertain the prospect of tumor-to-tumor metastasis. Thus, a comprehensive pathologic study of both tumors is highly recommended.
Topics: Humans; Carcinoma, Signet Ring Cell; Male; Rectal Neoplasms; Adult; Fatal Outcome; Lipoma; Adenocarcinoma, Mucinous
PubMed: 38884543
DOI: 10.1177/23247096241261309 -
Journal of Investigative Medicine High... 2024Metastasis to the pancreas from malignant tumors is a rare event, representing only 1% to 2% of all pancreatic neoplasms. They occur in 2 different clinicopathological...
Metastasis to the pancreas from malignant tumors is a rare event, representing only 1% to 2% of all pancreatic neoplasms. They occur in 2 different clinicopathological settings: as a manifestation in widespread metastatic disease or as an isolated mass in the pancreas. We report the case of a 41-year-old woman who had a history of invasive lobular breast cancer treated with radical surgery, chemotherapy, and radiotherapy. After 21 years of total remission, she presented for severe lower back pain with jaundice, nausea, and loss of 9 kg in 3 months. Abdominal computed tomography demonstrated a hyper vascularized, irregular solid lesion of 2.6 cm × 2.1 cm in the head of the pancreas with discreet biliary duct dilatation and coelio-mesenteric enlarged lymph nodes measuring 2 cm. The diagnosis of pancreatic metastasis from a lobular breast carcinoma was made by percutaneous biopsy of pancreatic lesion. The multidisciplinary committee decided a palliative treatment. The patient received chemotherapy. The take home message from his case is that we should keep in mind the hypothesis of a solitary metastasis to the pancreas, when the pancreatic lesion develops in a patient who had a clinical history of previous neoplasm especially in those which is known to potentially metastasize to pancreas.
Topics: Humans; Female; Pancreatic Neoplasms; Adult; Breast Neoplasms; Tomography, X-Ray Computed; Neoplasm Recurrence, Local; Diagnosis, Differential; Carcinoma, Lobular; Pancreas
PubMed: 38884538
DOI: 10.1177/23247096241261511