A case of pancreatic cancer treated with chemotherapy combined with immunotherapy and targeted therapy. / ä¸€ä¾‹åŒ–ç–—è”åˆå ç–«æ²»ç–—æ— æ•ˆèƒ°è ºç™Œæ‚£è€ å†è”åˆé¶å‘æ²»ç–—æœ‰æ•ˆ.

A 68-year-old male was admitted due to fatigue and poor appetite and diagnosed pathologically as pancreatic adenocarcinoma with liver metastasis. The tumor marker carbohydrate antigen 199 (CA199) level was 2003.4 U/mL. The patient received two cycles of modified FOLFIRINOX plus immune checkpoint inhibitor (penpulimab). However, the tumor did not shrink and CA199 level was even higher. Anlotinib was added from the 3rd cycle, and the size of primary tumor and metastatic lesions were significantly reduced. Laparoscopic distal pancreatectomy and splenectomy as well as liver metastasis resection was performed. Three cycles of combined therapy were adopted after surgery followed by maintenance therapy with anlotinib plus penpulimab. There was no evidence of tumor recurrence during the follow-up (nearly 19 months since diagnosis).

LncRNA SNHG20 silencing inhibits hepatocellular carcinoma progression by sponging miR-5095 from MBD1.

OBJECTIVE: Long non-coding RNAs (lncRNAs) may have a significant regulatory effect on the progression of hepatocellular carcinoma (HCC), according to recent data. This study aims to investigate how SNHG20, a small nucleolar RNA host gene, contributes to the development of HCC. METHODS: LncRNA SNHG20, miR-5095, and MBD1 gene levels were determined using reverse transcription qPCR (RT-qPCR). Huh-7 and HepG2 cell bioactivities were evaluated using the CCK-8 kit, EdU, flow cytometry, and wound-healing migration tests. To assess the metastasis of Huh-7 and HepG2 cells, a transwell assay was used. The amounts of invasion- and proliferation-associated proteins were determined using western blot. Using the miRDB (www.mirdb.org) software, the possible target genes of lncRNA and miRNA were predicted, and this prediction was then verified by a twofold luciferase reporter test. To determine the pathologic alteration and Ki67 level in tumor tissues, H&E staining and IHC were employed. TUNEL was conducted to assess the presence of apoptotic bodies in the tumor tissues. RESULTS: lncRNA SNHG20 exhibited a high expression in HCC cells (P<0.01). LncRNA SNHG20 knockdown inhibited HCC cell metastasis (P<0.01) and accelerated apoptosis (P<0.01). LncRNA SNHG20 acted as a sponge of miR-5095 in HCC. In addition, miR-5095 overexpression inhibited HCC cell metastasis (P<0.01) and accelerated apoptosis (P<0.01); and miR-5095 negatively targeted MBD1. Furthermore, LncRNA SNHG20 regulated HCC progression through the miR-5095/MBD1 axis, and LncRNA SNHG20 knockdown inhibited HCC growth. CONCLUSION: LncRNA SNHG20 accelerates HCC progression by the miR-5095/MBD1 axis, indicating lncRNA SNHG20 can be used as a biomarker for patients with HCC.

Sequential therapy for pancreatic cancer patients with synchronous oligo-hepatic metastatic lesions.

BACKGROUND: Treatments for patients suffering from pancreatic cancer with oligo-hepatic metastasis have always been a cause of certain controversy. Herein, we reported 15 pancreatic cancer patients with oligo-hepatic metastasis who accepted sequential therapy of chemotherapy, radiofrequency ablation (RFA), and radical resection of the primary tumor. METHODS: A total of 87 pancreatic cancer patients with synchronous oligo-metastatic hepatic lesions who received treatments in the 2nd Affiliated Hospital of Zhejiang University between January 2017 and July 2020 were enrolled. The chemotherapy regimens included modified folfirinox (54/87) and gemcitabine plus nab-paclitaxel (33/87). Test of blood tumor markers and contrast-enhanced computed tomography (CT) or magnetic resonance (MR) scan was performed at diagnosis and after eight weeks of chemotherapy. RESULTS: Thirty-five patients received just chemotherapy because of poor reaction to the first round of chemotherapy(Overall survival (OS), 6.47±1.80 months); 15 patients reassessed as stable disease (SD)/partial response (PR) continued chemotherapy (OS, 10.35±3.15); nine patients reassessed as progressive disease (PD) after RFA and continued chemotherapy (OS, 10.90±2.60). The primary tumors in 13 patients were unresectable after chemotherapy and RFA (OS, 12.92±2.47), while 15 patients completed the sequential therapy of chemotherapy, radio-frequency ablation, and radical resection (OS, 16.76±6.55). CONCLUSIONS: Sequential chemotherapy and RFA is a good treatment strategy to select the best candidates for surgical treatment among patients with pancreatic cancer with oligo-hepatic metastasis.

Anti-PD-1-based immunotherapy plus lenvatinib to treat advanced gallbladder cancer in the elderly: a case series and review of current literature.

BACKGROUND: Gallbladder cancer (GBC) is a rare malignant tumour of the bile duct. Due to the lack of typical clinical manifestations in the early stage, it is basically at an advanced stage when discovered. Radical resection remains the only curative therapy for patients with GBC. The resection rate is relatively low due to tumour invasion and metastasis, and the overall prognosis is poor. For most patients with unresectable lesions, chemotherapy has been the only recommended treatment for decades. Immunotherapy combined with TKIs (tyrosine kinase inhibitors) was proven to be effective in patients with hepatocellular carcinoma and cholangiocarcinoma. Some physicians have attempted to apply immunotherapy and TKIs combined with traditional chemotherapy in patients with advanced GBC. However, the outcomes were not clear because limited cases were reported. CASE PRESENTATION: We present a case series of four elderly patients with advanced GBC who received tislelizumab and lenvatinib combined with chemotherapy. All four patients responded to this treatment approach. Tumour responses were better in Patient 1 (TMB-H, MSS), Patient 2 (low TMB, MSS), and Patient 3 (low TMB, MSI-H) than in Patient 4 (low TMB, MSS), in whom metastasis occurred during the later stage of treatment. CONCLUSION: The combination of tislelizumab and lenvatinib may be a promising treatment for patients with advanced GBC. The efficacy and safety need further confirmation.

Combination of Metformin and Sorafenib Induces Ferroptosis of Hepatocellular Carcinoma Through p62-Keap1-Nrf2 Pathway.

Hepatocellular carcinoma (HCC) is one of the most lethal cancers in the world. Sorafenib is the first small-molecule multi-kinase inhibitors approved by FDA for treatment of advanced HCC. Metformin has been demonstrated to have benefit for preventing cancer progression. In human recurrent HCCs, NF-E2-related factor 2 (Nrf2) was overexpressed and associated with poor survival. Nrf2 related signaling pathway plays central role to mediate cellular resistance to sorafenib through protecting HCC cells from ferroptosis. The effect of Combination treatment for HCC cells and the intrinsic mechanism have not been reported. In this study, metformin augmented the anti-tumor effect of sorafenib for HCC through ferroptosis induction by inhibiting Nrf2 related pathway. Based on the results of Nrf2 knockdown and p62 knockdown study, the combination of sorafenib and metformin suppressed proliferation of HCC cells through p62-Keap1-Nrf2/HO1 signaling way. Size of xenografts treated with the combination of sorafenib and metformin was smaller than other groups in vivo. Moreover, the combination treatment greatly induced ferroptosis in HCC cells through inhibiting Nrf2 expression. Based on our findings, the combination treatment suppressed proliferation of HCC cells through ferroptosis induction, by p62-Keap1-Nrf2/HO1 signaling way.

Efficacy and safety of FOLFIRINOX as second-line chemotherapy for advanced pancreatic cancer after gemcitabine-based therapy: A systematic review and meta-analysis.

OBJECTIVE: To undertake a meta-analysis of the treatment effects of different second-line chemotherapy regimens compared with FOLFIRINOX (FOL [folinic acid], F [fluorouracil], IRIN [irinotecan], OX [oxaliplatin]) after failure of gemcitabine-based first-line therapy in patients with pancreatic cancer. METHODS: This meta-analysis searched electronic databases, including Embase®, Medline, PubMed® and the Cochrane library, for eligible studies that reported the use of FOLFIRINOX and other drug regimens as second-line chemotherapy after failure of gemcitabine-based chemotherapy. Pooled analyses for progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR) and grade 3/4 treatment-emergent adverse events (TRAEs) were undertaken. RESULTS: The analysis included six studies with a total of 858 patients. Compared with the three other second-line regimens, FOLFIRINOX had a significantly longer PFS (hazard ratio [HR] 0.68, 95% confidence interval [CI] 0.52, 0.89) and OS (HR 0.71, 95% CI 0.59, 0.86); and a significantly better ORR (HR 0.43, 95% CI 0.23, 0.80) and DCR (HR 0.71, 95% CI 0.58, 0.88). However, grade 3/4 adverse events were more frequently reported in patients administered FOLFIRINOX compared with the other three regimens. CONCLUSION: FOLFIRINOX is recommended as a second-line chemotherapy regimen for patients with pancreatic cancer that have failed on gemcitabine-based first-line therapy.Research Registry number: reviewregistry1300.

Radiofrequency ablation versus traditional liver resection and chemotherapy for liver metastases from gastric cancer.

OBJECTIVE: To compare the short- and long-term outcomes of radiofrequency ablation (RFA) versus liver resection and chemotherapy for liver metastases from gastric cancer. METHODS: We retrospectively evaluated 50 patients who underwent curative gastrectomy and local treatments for liver metastases (RFA, n = 20; liver resection, n = 20; and chemotherapy, n = 10) from 2008 to 2018. RESULTS: The short- and long-term outcomes of each local treatment were evaluated. The median overall survival (OS) after RFA was similar to that after liver resection (20 vs. 20 months, respectively) and longer than that after chemotherapy (20 vs. 10 months, respectively). The 3-year OS and progression-free survival (PFS) rates after RFA were 20% and 10%, respectively, while those in the liver resection group were 23.5% and 23.5%, respectively. The 3-year OS rate after chemotherapy was 10%. The size and number of metastases were prognostic factors for patients with gastric cancer with liver metastasis without statistical significance. CONCLUSIONS: Among patients with liver metastasis from gastric cancer, OS and PFS were satisfactory and comparable between RFA and liver resection but better than those of chemotherapy. RFA is an appropriate option for patients with gastric cancer who have a solitary liver metastasis measuring ≤3.0 cm.

Successful treatment of a huge hepatic carcinoma with right portal vein thrombosis: A case report.

INTRODUCTION: Unlike the traditional associating liver partition and portal vein ligation for staged hepatectomy, it is still controversial whether patients with portal vein thrombosis can receive benefits from liver partition. PATIENT CONCERNS: Right upper abdominal distension for 2 months. DIAGNOSIS: Hepatocellular carcinoma with portal vein invasion INTERVENTION:: Radiofrequency-assisted liver partition with portal vein ligation (RALPP) OUTCOMES:: Disease-free survival: 3 months, overall survival: 7 months CONCLUSION:: Our results advocate this variation of RALPP for use in patients with huge HCC with portal vein invasion, without enough future liver remnant. Patients can receive benefits from the operation, including a shorter operation time, better recovery, and lower overall costs of the 2-stage procedure.

Acute lymphoblastic leukemia with pancreas involvement in an adult patient mimicking pancreatic tumor: A case report.

RATIONALE: Acute lymphoblastic leukemia (ALL) is a malignant disease originating from abnormal proliferation of B or T lymphocytes in bone marrow (BM). Invasion of the pancreas is extremely rare in adults. PATIENT CONCERNS: In this article, we report a case presenting that ALL invades the pancreas, as well as liver, kidney, and duodenum detected by magnetic resonance image. The patient was misdiagnosed as pancreatic tumor at initial since hemogram was unremarkable. DIAGNOSES: The diagnosis of ALL was established based on the endoscopic ultrasonography-guided fine-needle aspiration and bone marrow examination, showing BCR/ABL gene positive. INTERVENTIONS: The patient was actively treated with chemotherapy. Hematological remission was obtained and the lesions in the pancreas disappeared. OUTCOMES: The patient finally died of complication from fungal pneumonia and central nervous system involvement 12 months after diagnosis. LESSONS: Under the context of infection, persistent or intermittent fever and complete blood count are not significant prognoses of pancreatic involvement for adult with ALL. We hope that this case will help hepatobiliary and pancreatic surgeon to be aware of this kind of disease as pancreatic carcinoma and pancreas involvement by ALL have totally different treatment strategy.

A systematic review and meta-analysis of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) versus traditional staged hepatectomy.

It is still controversial whether associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) or traditional staged hepatectomy such as portal vein embolization (PVE) and 2-staged hepatectomy (TSH) is better. The aim of this study was to compare these 3 available strategies in extended hepatectomy.Trials were identified by searching MEDLINE, PubMed, the Cochrane Library, and Embase and additional articles were identified by hand searching. Comparative clinical studies reporting volumetric changes, mortality, morbidity, and feasibility of the second stage about ALPPS versus PVE or ALPPS versus TSH were included.Nine studies involving 557 patients met the inclusion criteria. Five studies reported on comparison of ALPPS and PVE, and the other 4 reported about ALPPS and TSH. In the comparison of ALPPS versus traditional staged hepatectomy (PVE and TSH), ALPPS was associated with a greater increase in the future liver remnant (FLR) (RR: 4.87; 95%CI, 3.41-6.33) and more frequent completion of stage 2 resection (RR: 1.32; 95%CI, 1.21-1.44). Compared with the traditional staged hepatectomy, ALPPS had a trend toward higher morbidity (RR: 1.19, 95%CI, 0.96-1.47) and mortality (RR: 2.11, 95%CI, 1.02-4.33) after stage 2 resection.ALPPS is associated with greater future liver remnant hypertrophy and a higher rate of completion of stage 2, but this may be at the price of greater morbidity and mortality.

Influence of thermal ablation of hepatic metastases from gastric adenocarcinoma on long-term survival: Systematic review and pooled analysis.

The objectives of this systematic review and pooled analysis were to examine long-term survival, morbidity, and mortality following thermal ablation of gastric cancer hepatic metastases and to identify prognostic factors that improve survival.Patients with hepatic metastases from gastric cancer are traditionally treated with palliative chemotherapy. Surgical resection is an alternative treatment of hepatic metastases. Whether patients can obtain benefit from thermal ablation of hepatic metastases is still controversial.A systematic literature search was undertaken (1990-2018). Publications were included if they studied more than 7 patients undergoing thermal ablation for hepatic metastasis from gastric cancer in the absence of peritoneal disease or other distant organ involvement. The primary outcome was the hazard ratio (HR) for overall survival. Comparison between thermal ablation and systematic chemotherapy or hepatic resection had been carried out. The influence of liver metastasis-related factors, such as <3 cm versus >3 cm, single versus multiple and metachronous versus synchronous upon survival was also assessed.The median survival of thermal ablation for the 12 studies included was 22.93[20.45-25.41] months. Procedures were associated with a median 30-day morbidity of 6% (0%-23%) and with no mortality. The median 1-year, 2-year, 3-year, and 5-year survival were 79.14%, 39.79%, 28.45%, and 19.46%, respectively. Thermal ablation of hepatic metastasis was associated with improved overall survival compared with systematic chemotherapy (HR = 2.12; 95% CI 0.77-3.47; P=.000). Meta-analysis confirmed the additional survival benefit of size <3 cm (HR = 1.46; 95% CI 1.03-1.88; P = .002) and receiving chemotherapy after thermal ablation (HR = 2.14; 95% CI 1.05-3.23; P = .000).A use of RFA/ microwave ablation (MWA) as a liver-directed treatment may provide greater survival benefit than chemotherapy and is an alternative option for the treatment of liver-only metastases from gastric cancer. With the appropriate selection of patients, such as tumors <3 cm in diameter, thermal ablation may provide better prognosis than hepatic resection of hepatic metastasis with lower morbidity and mortality. Postoperation chemotherapy should be provided to patients with GLM who received thermal ablation.

Laparoscopic combined with percutaneous ablation for hepatocellular carcinoma under liver capsule: A single Chinese center experience of thirty patients.

AIM OF STUDY: For the tumor lesions close to capsule of the liver, traditional percutaneous radiofrequency ablation (PRFA) is limited due to high incidence of postoperative complications. The aim of the present study is to whether laparoscopic combined with PRFA (LCPR) could effectively ablate the tumor lesions close to capsule of the liver. METHODS: A total of 119 patients with subcapsular hepatocellular carcinoma (HCC) were divided into two groups: PRFA group (89 patients) and LCPR group (30 patients). RFA was accomplished through cool-tip RFA system. For LCPR, PRFA was first carried out to destroy tumors deep inside the liver tissue. Then, laparoscopic RFA was performed under the guide of laparoscopic view and destroyed the superficial part of the tumor. Postoperative morbidity and technique effectiveness between two groups were evaluated. RESULTS: In PRFA group, the rate of fever was 70.8% (63/89), and two patients had gallbladder damage. Five patients had ascites. Pain was found in 26 patients (29.2%). In LCPR group, the rate of fever was 22/30 (73.3%). Two patients had ascites and only two patients complained of pain. In PRFA group, 77.5% (69/89) of the tumors were totally ablated, and in LCPR, 93.3% (28/30) of the tumors were destroyed without any residuals. CONCLUSION: LCPR could significantly reduce the incidence of postoperative pain and the rate of regional tumor residuals compared to the PRFA, suggesting this method could potentially be useful for subcapsular HCC ablation treatment.

Neoadjuvant therapy for patients with borderline resectable pancreatic cancer: A systematic review and meta-analysis of response and resection percentages.

BACKGROUND: We systematically reviewed and performed a meta-analysis of the available data regarding neoadjuvant chemo- and/or radiotherapy with special emphasis on tumor response/progression rates, toxicities, and clinical benefit, i.e. resection probabilities and survival estimates. METHODS AND FINDINGS: Trials were identified by searching PUBMED, MEDLINE, and the Cochrane Central Register of Controlled Trials from 1966 to Feb 2015. A total of 18 studies (n = 959) were analyzed. the estimated fraction of patients with complete response was 2.8% (CI 0.8-4.7%) and with partial response 28.7% (CI 18.9%-38.5%). Stable disease was averaged to 45.9% (CI 32.9%-58.9%) in all patients and tumor progression under therapy occurred by estimation in 16.9% (CI 10.2%-23.6%) of the patients. The weighted frequency of those who underwent resection was 65.3% (CI 54.2%-76.5%), and the proportion of R0 resection amounted to 57.4% (CI 48.2%-66.5%). The weighted mean of median survival amounted to 17.9 months (range: 14.7-21.2 months) for the overall cohort of patients, 25.9 months (range: 21.1-30.7 months) for those who were resected, and 11.9 months (range: 10.4-13.5 months) for unresected patients. CONCLUSIONS: The resection and R0 resection rates in the group of borderline resectable tumor patients after neoadjuvant therapy are similar to the resectable tumor patients, much higher than those in unresectable tumor patients. The survival estimates of borderline resectable tumor patients after neoadjuvant therapy were similar to resectable tumor patients. Patients with borderline resectable pancreatic cancer should be included in neoadjuvant protocols and subsequently be reevaluated for resection. How to find chemo-responsiveness before neoadjuvant chemotherapy so as to give individualized treatment is still an important issue.

Preliminary Study on Hepatocyte-Targeted Phosphorus-31 MRS Using ATP-Loaded Galactosylated Chitosan Oligosaccharide Nanoparticles.

Background. The clinical applications of hepatic phosphorus-31 magnetic resonance spectroscopy (31P MRS) remain to be difficult because the changes of phosphates between normal hepatic tissues and pathological tissues are not so obvious, and furthermore, up to now there is few literature on hepatocyte-targeted 31P MRS. Materials and Methods. The ATP-loaded Gal-CSO (Gal-CSO/ATP) nanoparticles were prepared and the special cellular uptake of them as evaluated by using HepG-2 tumor cells and A549 tumor cells, respectively. Two kinds of cells were incubated with the nanoparticles suspension, respectively. Then were prepared the cell samples and the enhancement efficiency of ATP peaks detected by 31P MRS was evaluated. Results. The cellular uptake rate of Gal-CSO/ATP nanoparticles in HepG-2 cells was higher than that in A549 cells. Furthermore, the enlarged ATP peaks of Gal-CSO/ATP nanoparticles in HepG-2 cells were higher than those in A549 cells in vitro detected by 31P MRS. Conclusions. Gal-CSO/ATP nanoparticles have significant targeting efficiency in hepatic cells in vitro and enhancement efficiency of ATP peaks in HepG-2 cells. Furthermore, 31P MRS could be applied in the research of hepatic molecular imaging.