Recent advances in the understanding of the mechanisms responsible for tumor progression suggest the possibility to control cancer growth, not only through chemotherapy-induced cancer cell destruction, but also by stimulating anticancer immunity. However, immune tolerance against tumor antigens disturbs diverse forms of immunotherapy. One of the most potent and well-studied tumor-induced immunosuppressive phenotypes found in the tumor microenvironment is the regulatory subpopulation cells (CD4+CD25+FoxP3+ Treg cells). Among the great number of natural agents derived from plants and potentially useful for application in the complementary therapy of cancer, resveratrol is gaining attention for its immunomodulating properties in breast cancer, since the ineffectiveness of numerous immunotherapy strategies may be related, in part, to their negative effects on Treg cells. The present study was undertaken to examine whether HS-1793, a synthetic resveratrol analogue free from the restriction of the metabolic instability and high dose requirement of resveratrol, shows a direct effect on immune responses by enhancing lymphocyte proliferation or an immunomodulatory effect by inducing changes in the Treg cell population in FM3A breast tumor-bearing mice. Although HS-1793 had no direct immunostimulatory effect, it dose-dependently decreased IL-2 secretion and increased IL-4 secretion of concanavalin A-stimulated lymphocytes from tumor-bearing mice, which suggest that HS-1793 may induce changes in the subpopulations of tumor-derived T lymphocytes. The CD4+CD25+ cell population from tumor-bearing mice decreased after HS-1793 treatment in a dose-dependent manner, while the CD4+ T cell population remained unchanged. FoxP3+-expressing cells among the CD4+CD25+ population showed a similar pattern. In contrast, the CD8+ T cell population as well as the interferon (IFN)-γ-expressing CD8+ T cell population and IFN-γ secretion of splenocytes from tumor-bearing mice were significantly upregulated by HS-1793 treatment. These results suggest that HS-1793 induces the modulation of tumor-derived T lymphocytes, particulary having a suppressive effect on the Treg cell population, likely contributing to enhanced tumor-specific cytotoxic T lymphocyte responses and CD4+ T cells involving antitumor immunity. Therefore, HS-1793 may serve as a promising adjuvant therapeutic reagent in breast cancer immunotherapy.
Background: Liver resection has been established as a curative treatment for various hepatic tumors.However, severe post-hepatectomy liver failure (PHLF) is a major cause of mortality and factor in choosing non-surgical palliative treatment.Postoperative excessive portal pressure could cause shear stress to the small remnant liver after extensive liver resection as contributing factor for developing the PHLF.This study aimed to report a prospective clinical trial to evaluate somatostatin's effect as pharmacologic portal modulation for severe PHLF.Methods: This prospective study enrolled 20 patients who received somatostatin for the treatment of PHLF between 2016 and 2021.When the patients fulfilled the 50-50 criteria (serum bilirubin > 2.9 mg/dL and prothrombin time < 50%) on or before postoperative day 5, somatostatin (3.5 ug/kg/h) was administered by continuous infusion.The discontinuation criteria were as follows: serum bilirubin < 2 mg/dL and prothrombin time ≥ 50%.Prospectively collected clinical characteristics, laboratory tests, postoperative morbidity, and mortality were evaluated.Results: Among the study cohort, 17 (85.0%)patients underwent major liver resection with the extent above right hemihepatectomy, and 3 (15.0%)underwent preoperative right portal vein embolization.The median ICG-R15 was 13.0 (range 6.8-56.1),and the MELD score was 10 (6-24).After the operation, somatostatin was started on a postoperative day 1 (1-19) and was administered for 9 (2-29) days.There were no obvious side effects related to the somatostatin.The median hospital stay was 33 (8-249) days.The 30-day and 90day mortality were both 10.0 %, and 17 (85.0%)patients recovered from severe PHLF.Conclusions: Administration of somatostatin in the early postoperative period is considered safe and effective for the treatment of PHLF.Further large-scale comparative clinical trials are needed to validate this finding.
Background: With the introduction of effective systemic chemotherapy regimens for pancreatic cancer, many recent studies have been reported improved survival outcomes after surgery.Therefore, it is crucial to evaluate the response after chemotherapy using appropriate diagnostic tests to determine the subsequent treatment method, conversion to surgery or further chemotherapy.In this study, the positron emission tomography (PET) parameters before and after neoadjuvant chemotherapy were compared and factors affecting the survival outcome of the patients were investigated.Methods: Among the patients histologically diagnosed with pancreatic ductal adenocarcinoma (PDAC) who underwent therapeutic pancreatectomy from September 2012 to February 2020, received at least 4 cycles of neoadjuvant chemotherapy and took PET images before and after treatment were included.The medical records of 94 patients included in the study were reviewed and the PET parameters, such as max, peak, mean standardized uptake value (SUV), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were calculated and statistically analyzed.Results: At the time of diagnosis, 46 patients (48.9%) were borderline resectable, and 25 patients (26.6%) were locally advanced.74 patients (78.2%) received FOLFIRINOX regimen preoperatively.The survival outcomes were compared based on TLG value measured after chemotherapy as 55, TLG less than 55 group showed superior survival results (overall survival: 56 vs. 21 months, p = 0.006).This factor was confirmed as hazard ratio 2.450 [95% confidence interval 0.986-6.088] in multivariate analysis (p = 0.054).Conclusions: After neoadjuvant chemotherapy in pancreatic cancer patients, PET parameters can be used to predict the prognosis.Further validation through large-scale studies is required.
Background: Insulinomas are rare pancreatic islet cell tumors.The clinical manifestation of an insulinoma is fasting hypoglycemia, with neuroglycopenic symptoms that may or may not be preceded by sympathoadrenal (autonomic) symptom.Malignant insulinomas only constitute 5 to 10% of all the insulinomas.We report a rare case of malignant insulinoma with multiple large liver metastasis.Methods: (case presentation) A 25-year-old female was referred to our hospital for persistent symptoms of hypoglycemia, such as dizziness and events of syncope.She had had no specific medical history before.On initial examination, computed tomography showed an about 10cm sized hypervascular mass and other small multiple masses in the right lobe of liver.The primovist liver MRI also presented two small metastases in S3 and S5 segments of liver.The laboratory tests showed serum glucose, immunoreactive insulin, and C peptide concentrations of 33 mg/dL, 23.22 uIU/mL, 3.64 ng/mL, respectively.However, we could not find the pancreatic mass until positron emission tomography (PET), focal hypermetabolic lesion in pancreatic tail portion, multiple liver masses with irregular hypermetabolism and no other definite abnormal hypermetabolic lesions.The endoscopic ultrasonography was performed to find the pancreatic mass on tail, but it was too small to localize the pancreatic tumor.The sono-guided needle biopsy on the huge liver mass was performed and confirmed with neuroendocrine tumor.Results: The initial possible diagnosis was primary hepatic insulinoma or pancreatic insulinoma with multiple liver metastasis.Since there was no distant metastasis, we decided surgical resection of all tumors.Right hepatectomy, S1 segmentectomy, radiofrequency ablation tumor on segment 3 and segment 4 (6 mm sized mass) and distal pancreatectomy were performed.The final diagnosis is stage IV pancreatic tail insulinoma confined liver metastasis (AJCC and UICC 8th edition).She has been free of symptoms of hypoglycemia and radiologic findings of recurrence of insulinoma 3-month after surgery.Conclusions: Malignant insulinoma is extremely rare and surgical resection is the treatment of choice despite of metastasis.In this case, localizing primary tumor in pancreas was challenging.With successful removal of all possible tumors, the patient was relieved from the hypoglycemic symptoms.Thus, aggressive surgical resection should be considered for malignant insulinoma.
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