Advanced Pancreatic Carcinoma Research Articles

DR30318, a novel tri-specific T cell engager for Claudin 18.2 positive cancers immunotherapy

BackgroundClaudin 18.2 (CLDN18.2) is a highly anticipated target for solid tumor therapy, especially in advanced gastric carcinoma and pancreatic carcinoma. The T cell engager targeting CLDN18.2 represents a compelling strategy for enhancing anti-cancer efficacy.MethodsBased on the in-house screened anti-CLDN18.2 VHH, we have developed a novel tri-specific T cell engager targeting CLDN18.2 for gastric and pancreatic cancer immunotherapy. This tri-specific antibody was designed with binding to CLDN18.2, human serum albumin (HSA) and CD3 on T cells.ResultsThe DR30318 demonstrated binding affinity to CLDN18.2, HSA and CD3, and exhibited T cell-dependent cellular cytotoxicity (TDCC) activity in vitro. Pharmacokinetic analysis revealed a half-life of 22.2–28.6 h in rodents and 41.8 h in cynomolgus monkeys, respectively. The administration of DR30318 resulted in a slight increase in the levels of IL-6 and C-reactive protein (CRP) in cynomolgus monkeys. Furthermore, after incubation with human PBMCs and CLDN18.2 expressing cells, DR30318 induced TDCC activity and the production of interleukin-6 (IL-6) and interferon-gamma (IFN-γ). Notably, DR30318 demonstrated significant tumor suppression effects on gastric cancer xenograft models NUGC4/hCLDN18.2 and pancreatic cancer xenograft model BxPC3/hCLDN18.2 without affecting the body weight of mice.

Abstract 5183: Retrospective analysis of CCNG1 expression in tumors, a novel biomarker in development for partnering with DRG-101, a tumor targeted retrovector encoding a CCNG1 inhibitor gene

Abstract Background: CCNG1, a non-canonical cyclin, is a novel biomarker in development for partnering with DRG-101 (DeltaRex-G), a tumor targeted retrovector encoding a CCNG1 inhibitor gene. Expanded access using DRG-101 is currently open for an intermediate-size population of advanced pancreatic cancer, sarcoma and carcinoma of breast (NCT04091295). Therefore, it is important to identify patients who might respond favorably to DRG-101 gene therapy. Previously, we reported that CCNG1 expression is enhanced in sarcoma tumors (Ann Oncol 34, 1980P, 2023). In this report, we have expanded the analysis to 137 patients with all cancer types and describe patients with known CCNG1 expression levels who have been treated with DRG-101. Methods: Archived formalin-fixed paraffin-embedded (FFPE) tumor specimens (n=137) from patients who were followed at the Sarcoma Oncology Research Center were collected, processed, and subjected to RNA sequencing. Briefly, RNA-seq libraries were sequenced to generate 50 million reads, aligned using Kallisto v0.42.4 to GENCODE v23 transcripts with default parameters. Only protein-coding, IGH/K/L- and TCR-related transcripts were retained for downstream processing, resulting in 20,062 protein-coding genes. Gene expression levels in patients of the reference cohorts are categorized as low/medium/high, defined by Low = < 17%; Medium-high = 50%-83%; Medium-low = 17%-49%; High = >83%. Results: Seventy women and sixty-seven men, ranging in age from 16 to 87 years, were studied. All tumors showed enhanced CCNG1 expression. Thirty (22%) tumors exhibited high CCNG1 expression, 53 (39%) showed medium-high CCNG1 expression, 48 (35%) displayed medium-low CCNG1 expression, and six (4%) had low CCNG1 expression. One hundred (73%) patients had metastatic disease, and 37 (27%) had localized disease. There was no correlation between CCNG1 expression and disease stage. As a result of these findings, the FDA-CBER authorized the use of DRG-101 in an Expanded Access program as platform therapy upon which one or more FDA approved cancer drugs/immunotherapies may be added. Historically, one patient with metastatic pancreatic cancer, one with early stage, HR+ HER2+ invasive breast cancer and one with early stage triple negative breast cancer are alive 15, 3 and 2.5 years in sustained remission with DRG-101 therapy, and had 24%, 23% and 74% CCNG1 tumor expression levels respectively. Five patients with advanced pancreatic cancer, sarcoma and breast cancer and known CCNG1 expression levels are currently being treated with DRG-101. Conclusions:(1) 100% of tumors tested showed enhanced CCNG1 expression at varying levels, and (2) the use of DRG-101 in combination with FDA approved cancer drugs/immunotherapies is on-going for an intermediate size population of advanced pancreatic cancer, sarcoma and carcinoma of breast. Citation Format: Nadezhda Omelchenko, Vaishali Kumar, Samantha Jeffrey, Grace Haroun, Don Brigham, William H. Isacoff, Sant Chawla. Retrospective analysis of CCNG1 expression in tumors, a novel biomarker in development for partnering with DRG-101, a tumor targeted retrovector encoding a CCNG1 inhibitor gene [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5183.

The CSF-1R inhibitor pexidartinib affects FLT3-dependent DC differentiation and may antagonize durvalumab effect in patients with advanced cancers.

Tumor-associated macrophages (TAMs) are a critical determinant of resistance to PD-1/PD-L1 blockade. This phase 1 study (MEDIPLEX, NCT02777710) investigated the safety and efficacy of pexidartinib, a CSF-1R-directed tyrosine kinase inhibitor (TKI), and durvalumab (anti-PD-L1) in patients with advanced colorectal and pancreatic carcinoma with the aim to enhance responses to PD-L1 blockade by eliminating CSF-1-dependent suppressive TAM. Forty-seven patients were enrolled. No unexpected toxicities were observed, one (2%) high microsatellite instability CRC patient had a partial response, and seven (15%) patients experienced stable disease as their best response. Increase of CSF-1 concentrations and decrease of CD14lowCD16high monocytes in peripheral blood mononuclear cells (PBMCs) confirmed CSF-1R engagement. Treatment decreased blood dendritic cell (DC) subsets and impaired IFN-λ/IL-29 production by type 1 conventional DCs in ex vivo TLR3-stimulated PBMCs. Pexidartinib also targets c-KIT and FLT3, both key growth factor receptors of DC development and maturation. In patients, FLT3-L concentrations increased with pexidartinib treatment, and AKT phosphorylation induced by FLT3-L ex vivo stimulation was abrogated by pexidartinib in human blood DC subsets. In addition, pexidartinib impaired the FLT3-L- but not GM-CSF-dependent generation of DC subsets from murine bone marrow (BM) progenitors in vitro and decreased DC frequency in BM and tumor-draining lymph node in vivo. Our results demonstrate that pexidartinib, through the inhibition of FLT3 signaling, has a deleterious effect on DC differentiation, which may explain the limited antitumor clinical activity observed in this study. This work suggests that inhibition of FLT3 should be considered when combining TKIs with immune checkpoint inhibitors.

Peak Risk of Recurrence Occurs during the First Two Years after a Pancreatectomy in Patients Receiving Neoadjuvant FOLFIRINOX

No codified/systematic surveillance program exists for borderline/locally advanced pancreatic ductal carcinoma treated with neoadjuvant FOLFIRINOX and a secondary resection. This study aimed to determine the trend of recurrence in patients who were managed using such a treatment strategy. From 2010, 101 patients received FOLFIRINOX and underwent a pancreatectomy, in a minimum follow-up of 5 years. Seventy-one patients (70%, R group) were diagnosed with recurrence after a median follow-up of 11 months postsurgery. In the multivariable analysis, patients in the R-group had a higher rate of weight loss (p = 0.018), higher carbohydrate antigen (CA 19-9) serum levels at diagnosis (p = 0.012), T3/T4 stage (p = 0.017), and positive lymph nodes (p < 0.01) compared to patients who did not experience recurrence. The risk of recurrence in patients with T1/T2 N0 R0 was the lowest (19%), and all recurrences occurred during the first two postoperative years. The peak risk of recurrence for the entire population was observed during the first two postoperative years. The probability of survival decreased until the second year and rebounded to 100% permanently, after the ninth postoperative year. Close monitoring is needed at reduced intervals during the first 2 years following a pancreatectomy and should be extended to later than 5 years for those with unfavorable pathological results.

1617P PRODIGE 29-UCGI 26 (NEOPAN): Quality of life results of a phase III randomised trial comparing chemotherapy with folfirinox (FFX) or gemcitabine (gem) in locally advanced pancreatic carcinoma (LAPC)

1617P PRODIGE 29-UCGI 26 (NEOPAN): Quality of life results of a phase III randomised trial comparing chemotherapy with folfirinox (FFX) or gemcitabine (gem) in locally advanced pancreatic carcinoma (LAPC)

Surgical pancreatic biopsies for cases with locally advanced pancreatic cancer with inconclusive histology after interventional biopsy

BackgroundHistopathological confirmation of malignancy is mandatory in patients with unresectable pancreatic cancer before initiation of palliative chemotherapy. When interventional biopsy proves unsuccessful, laparoscopic or open surgical biopsies become necessary. Methods66 consecutive surgical biopsies of the pancreas performed at a single institution between 01/2010 and 04/2020 were analyzed retrospectively. We analyzed sensitivity of histopathological confirmation of malignancy as well as complication rates of laparoscopic and open surgical biopsies in patients with suspected advanced pancreatic cancer after unsuccessful interventional biopsies. Results8 complications were observed in 46 patients requiring only a pancreatic biopsy (17.4 %) while in 13 of 20 patients complications were observed when additional procedures were necessary (65 %). Major complications CD ≥ III were observed in the “biopsy +/- port” group in 4 of 46 patients and in the “biopsy + additional procedure” cohort in 9 of 20 patients (8.7 vs. 45 %, p < 0.001). Despite the trend to reduced perioperative complications in laparoscopic biopsies, the reduction did not reach statistical significance when compared to open resections (11.1 vs. 26.3 %, p = 0.18). Surgical pancreatic biopsies reached a sensitivity regarding the correct definite histopathological result of 90.32 %, specificity was 100 %. ConclusionBoth laparoscopic and open biopsies can be performed at acceptable complication rates CD ≥ III of 8.7 % and present a valuable option after failure of image-guided techniques for biopsy. Additional operative measures in locally advanced pancreatic carcinoma ought to be critically reflected due to a substantially higher complication rate CD ≥ III of 45 %. Key messageLaparoscopic and open surgical biopsies in patients with unresectable pancreatic cancer demonstrate a high diagnostic sensitivity at acceptable complication rates. This finding is important because it provides further support for surgical biopsies to avoid delay before initiation of palliative therapy.

Histologic changes of porcine portal vein anastomosis after electrochemotherapy with bleomycin

Electrochemotherapy (ECT11Electrochemotherapy.) is used for treatment of unresectable abdominal malignancies. This study aims to show that ECT of porcine portal vein anastomosis is safe and feasible in order to extend the indications for margin attenuation after resection of locally advanced pancreatic carcinoma. No marked differences were found between the control group and ECT treated groups. Electroporation thus caused irreversible damage to the vascular smooth muscle cells in tunica media that could bedue to the narrow irreversible electroporation zone that may occur near the electrodes, or due to vasa vasorum thrombosis in the tunica externa. Based on the absence of vascular complications, and similar histological changes in lienal veinanastomosis, we can conclude that ECT of portal vein anastomosis is safe and feasible.

A phase II study of olaparib (AZD2281) in patients (Pts) with metastatic/advanced urothelial carcinoma and other genitourinary (GU) tumors with DNA-repair defects.

TPS4607 Background: Olaparib is a poly-ADP-ribose polymerase (PARP) inhibitor that induces synthetic lethality in tumor cells with dysfunctional DNA damage repair (DDR) from loss of function of BRCA or other DDR genes. It improves survival in advanced ovarian, pancreatic, prostate and breast carcinoma with DDR gene alterations and is FDA approved for these indications. PARP inhibitors still have an undefined role in non-prostate GU tumors. We hypothesize that PARP inhibitors will have activity in DDR deficient tumors, regardless of histology. We are conducting a phase 2 trial of olaparib in non-prostate GU cancers with DDR gene defects. Methods: Eligible pts must have metastatic/advanced urothelial carcinoma or other non-prostate GU cancers and have measurable disease by RECIST 1.1. Pts in Cohorts 1 and 2 must harbor tumor or liquid pathologic DDR alterations identified by FoundationOne CDx (F1CDx) panel and reviewed by a molecular genetics review panel: Cohort 1 includes BRCA1, BRCA2, ATM, BAP1, MSH2, PALB2, and BRIP1 alterations, and pts with high tumor mutational burden (TMB) (&gt;15 mutations/megabase); Cohort 2 (exploratory cohort) includes ABL1, ATR, ATRX, BARD1, BRD4, CCND1, CHEK1, CHEK2, DOTIL, FANCC, FANCE, FANCG, FANCL, IKBKE, MEN1, MLH1, MSH2, MSH6, MUTYH, NPM1, PMS2, POLD1, POLE, RAD51, SMARCB1, STEK11, and TP53 alterations. Cohort 3 (natural history) will include pts without pathologic alterations in any Cohort 1 or 2 genes. Pts with eligible gene alterations (Cohorts 1 and 2) will be given olaparib 300mg twice daily until progressive disease, unacceptable adverse events, withdrawal of consent or death. They will have circulating tumor cells (CTCs) collected at baseline and every 4 weeks, and CT restaging every 8 weeks. Pts in Cohort 3 will receive standard of care treatment and have baseline CTC collection and be followed for survival. The primary objective is to evaluate the objective response rates (ORR) in Cohorts 1 and 2. Secondary objectives include progression-free survival (PFS), overall survival (OS) and safety. In these cohorts, the trial will have a Simon optimal two-stage design. In Cohort 1, 25 evaluable pts will be required to provide 90% power with alpha = 0.1 to differentiate between a promising ORR of 30% versus an unacceptably low ORR of 10%. In Cohort 2, 35 evaluable pts will be required to provide 90% power with alpha = 0.05 to differentiate between a promising ORR of 30% versus an unacceptably low ORR of 10%. Exploratory objectives include estimating the distribution of DDR alterations in non-prostate GU malignancies, assessing the effectiveness of NGS in detecting DDR alterations in circulating tumor DNA (ctDNA), assessing levels of baseline CTCs and changes in CTC level with olaparib, and correlating with clinical outcomes. This is an ECTCN network clinical trial and is open to enrollment. Clinical trial information: NCT03375307 .

Textbook outcomes among patients undergoing curative resection of pancreatic ductal adenocarcinoma in the era of neoadjuvant therapy

BackgroundNeoadjuvant therapy has been the standard care for borderline resectable or locally advanced pancreatic ductal carcinoma (BR/LA PDAC). The textbook outcome (TO) for curative resection after neoadjuvant therapy (NAT) remains understudied. MethodPatients underwent curative resection for PDAC between 2019 and 2020 were confirmed from the multidisciplinary team (MDT) database prospectively maintained by the Department of Pancreatic Hepatobiliary Surgery of Changhai hospital. TO of patients received NAT was compared to those received upfront surgery (UFS), and multivariate analysis of clinicopathological parameters was performed to explore predictors for TO. ResultsOf 435 patients, 329(76%) patients received UFS whereas 106(24%) patients received NAT. The TO was 82.1% for the NAT cohort, 77.8% for pancreaticoduodenectomy (PD) and 86.8% for distal pancreatectomy (DP). In the UFS cohort, the TO was 73.3% overall, 70.6% for PD and 77.3% for DP. Patients in the NAT cohort had longer time of operation, more intra-operative blood loss and more vascular resection. However, TO of the NAT cohort were not statistically different compared to that in the UFS cohort (p ​= ​0.27 for PD and p ​= ​0.20 for DP). On multivariable analysis, only diabetes-free was predictive for a better TO rate after PD in the UFS cohort(p ​= ​0.003). There were no factors associated with TO after DP in the UFS cohort, nor after PD or DP in the NAT cohort. ConclusionAs a composite indicator of desired surgical outcome, TO for curative resection after neoadjuvant therapy is similar to that in upfront surgery. All patients with stable or regressed tumors after NAT should be candidates for curative resection in an MDT setting.

Assessment of biological effect of nab-paclitaxel combined with gemcitabine, using contrast enhanced ultrasonography and elastography, in advanced pancreatic ductal carcinoma: A single-center pilot study.

EUS associated with contrast-enhanced harmonic EUS (CH-EUS) and EUS elastography (EUS-E) are used in clinical practice to assess pancreatic tumor at the diagnosis. In case of pancreatic ductal adenocarcinoma (PDAC) with liver metastasis, nab-paclitaxel combined with gemcitabine is a first-line treatment option. We aimed to assess the modification of PDAC microenvironment induced by the combination of nab-paclitaxel with gemcitabine, by endoscopic ultrasonography techinics. This single center phase III study conducted between February 2015 and June 2016 included patients with pancreatic adenocarcinoma with mesurable liver metastasis and no prior cancer treatment fit for two cycles of nab-paclitaxel combined with gemcitabine. We aimed to perform EUS with CH-EUS and EUS-E of the pancreatic tumor, CT scan and contrast enhanced ultrasonogram (CE-US) of a reference liver metastasis, before and after the two cylces of chemotherapy. Primary end point was modification of vascularizaion of primary tumor and a reference liver metastasis. Secondary end points were modification of stromal content, safety profile of drug combination and tumor response rate. Sixteen patients were analyzed, but only 13 received two cycled of chemotherapy (CT) (toxicity [n = 1] or death [n = 2]). There was no statistical modification induced by CT concering vascularity of primary tumor (time to maximum intensity P = 0.24, value of maximum intensity P = 0.71, hypoechogenic aspect generated by injection of contrast enhancing agent), vascularity of a reference liver metastasis (time to maximum intensity P = 0.99, value of maximum intensity P = 0.71) and tumor elasticity (P = 0.22). Eleven patients had tumor response assessement, 6/11 (54%) had measurable disease response 4/11 (36%) with partial responses and 2/11 (18%) with stable disease. All other patients showed disease progression. No serious side effects occurred, 6/11 patients had a dose adjustment. We did not show significant modification of vascularity and elasticity but these results should be taken with caution because of important limitations.

Chemotherapy versus chemoradiotherapy in borderline resectable and locally advanced pancreatic adenocarcinoma.

The role of radiotherapy in borderline resectable (BRPC) and locally advanced pancreatic carcinoma (LAPC) remains controversial. In our study, we retrospectively evaluated 48 patients with BRPC (14; 29.2%) and LAPC (34; 70. 8%) who underwent 6-8 cycles of induction mFOLFIRINOX chemotherapy alone (23; 47.9%) or 4-6 cycles of mFOLFIRINOX followed by hypofractionated radiotherapy (up to the total dose of 39.9 Gy in 15 fractions) (25; 52.1%). Survival parameters were evaluated using the Gehan-Breslow-Wilcoxon Test and compared by using the long-rank test. The addition of radiotherapy was not associated with better survival (16.9 months for chemotherapy only versus 15.9 months for the combined therapy; p=0.486), as well as for both subgroups (13.5 months vs. 18.3 months; p=0.679) and (20.7 months vs. 13.8 months; p=0.425) for BRPC and LAPC, respectively. A higher resection rate was seen in the BRPC group compared to the LAPC group (43% vs. 17.6%, respectively). Our study revealed a significantly higher rate of lung metastases in patients after the combination therapy compared to those treated by chemotherapy only (19% vs. 0%, respectively; p=0.045). Such a borderline result, however, prevents us from drawing clear conclusions about whether this is an artifact caused by the low number of patients or whether radiotherapy leads to a selection of stem cells with a predilection to the generalization to the lungs.

Germline BRCA2 variants in advanced pancreatic acinar cell carcinoma: A case report and review of literature

Germline BRCA2 variants in advanced pancreatic acinar cell carcinoma: A case report and review of literature

A composite indicator of derived neutrophil-lymphocyte ratio and lactate dehydrogenase correlates with outcomes in pancreatic carcinoma patients treated with PD-1 inhibitors.

There are currently no established biomarkers that can predict whether advanced pancreatic carcinoma (PC) patients would benefit from immune checkpoint inhibitors (ICIs). Our study investigated whether the pretreatment composite biomarker of derived neutrophil-lymphocyte ratio (dNLR) and lactate dehydrogenase (LDH) can be used as a reliable prognostic factor for the survival of PC patients receiving PD-1 inhibitor therapy. Patients with advanced PC treated with PD-1 inhibitors at a single center from September 2015 to September 2020 were included. The high levels of dNLR (≥3) and LDH (≥250 U/L) were considered to be risk factors. Based on these two risk factors, patients in this study were categorized into two risk groups: the good dNLR-LDH group, without risk factors, and the intermediate/poor dNLR-LDH group, with one to two risk factors. Overall survival (OS) and progression-free survival (PFS) served as this study's primary and secondary endpoints. Cox regression models were used to identify independent prognostic factors for survival benefit. There were 98 patients in our study. The good group included 61 (62.2%) patients and the intermediate/poor group included 37 (37.8%). The overall patients with PC who received immunotherapy had a median OS of 12.1 months, and the good dNLR-LDH group had a significantly longer OS compared with the intermediate/poor dNLR-LDH group (44.2 vs. 6.4 months; p < 0.010); median PFS was 3.7 and 2.5 months (p = 0.010). The number of metastatic sites >2 and immunotherapy as third-line or later was associated with worse PFS, and the line of immunotherapy and the dNLR-LDH indicator were independent prognostic factors for OS, according to multivariate analysis. The pretreatment composite biomarker of dNLR and LDH can be used as a prognostic biomarker in patients with advanced PC treated with PD-1 inhibitors.

Outcome of metal vs plastic stents for biliary obstruction in patients with pancreatic carcinoma undergoing neoadjuvant chemoradiotherapy: A systematic review and meta-analysis.

Preoperative biliary drainage (PBT) may be warranted in patients with borderline resectable or locally advanced pancreatic carcinoma before neoadjuvant therapy (NAT) to relieve obstructive jaundice. However, it is unclear if the use of self-expanding metal stents (SEMS) has any benefit over plastic stents in this setting. We searched electronic databases from inception to February 11, 2022 to identify studies comparing SEMS and plastic stents for PBT in patients with pancreatic carcinoma undergoing NAT. Random effect models were used to determine pooled rates of recurrent biliary obstruction (RBO) and/or need for reintervention, stent-related complications and surgical outcome. A total of 10 studies (474 patients; metal group-37.1%) were included. Pooled risk ratio of RBO and/or need for reintervention was lower in the metal group (RR, 0.23 [95% CI: 0.11-0.45, I2 = 60%]). Pooled risks of stent occlusion (RR, 0.43 [95% CI: 0.24-0.80, I2 = 45%]) and stent-related cholangitis (RR, 0.37 [95% CI: 0.17-0.78, I2 = 1%]) were lower in the metal group. However, risks of stent-related cholecystitis (RR, 1.51 [95% CI: 0.36-6.41, I2 = 0%]) and pancreatitis (RR, 1.52 [95% CI: 0.07-31.84, I2 = 66%]) were higher in the metal group. The metal group was also associated with a reduced risk of delay in NAT (RR, 0.38 [95% CI: 0.18-0.80, I2 = 14%]). Pooled risk ratio of R0 resection and postoperative complications was equal amongst both groups. Metal stents are associated with reduced risk of RBO and/or need for reintervention, reduced risk of stent occlusion and cholangitis as compared to plastic stents in patients with pancreatic carcinoma undergoing NAT.

1296MO PRODIGE 29-UCGI 26(NEOPAN): A phase III randomised trial comparing chemotherapy with folfirinox or gemcitabine in locally advanced pancreatic carcinoma (LAPC)

Pancreatic carcinoma (PC) is an aggressive malignancy and the 4th cause of all cancer deaths worldwide. More than 30% of patients with PC are unresectable because of the local extension with a median overall survival (OS) of less than one year. Folfirinox (FFX) is superior to gemcitabine in the treatment of metastatic PC, in terms of OS and progression-free survival (PFS) but standard of care remains gemcitabine (gem) for LAPC.

Biohumoral Predictors of Advanced Pancreatic Carcinoma Not Shown at Pre-operative Imaging

Biohumoral Predictors of Advanced Pancreatic Carcinoma Not Shown at Pre-operative Imaging

Brachytherapy Drainage Catheter and Chemotherapy for Unresectable Pancreatic Carcinoma Combined with Obstructive Jaundice.

BackgroundMost patients with advanced pancreatic cancer do not have the chance to undergo surgery or chemotherapy because of their poor conditions. Biliary drainage is a palliative treatment to restore liver function and alleviate jaundice, but most patients still face the risk of biliary obstruction in the short term after operation. The purpose of this study is to evaluate the efficacy and safety of brachytherapy drainage catheter (BDC)-combined chemotherapy in the treatment of pancreatic cancer complicated with obstructive jaundice.Patients and MethodsFrom November 2017 and May 2019, 48 patients underwent the BDC or conventional drainage catheter (CDC) intervention with chemotherapy. The outcomes/endpoints analyzed were technical and clinical success, early complications, stent patency period, and survival.ResultsThe technical and clinical success rates in both groups were 100%, and the early complication rates were not significantly different (P = 0.43). The median stent patency in the BDC group was significantly longer than that in the CDC group (7.8 ± 1.5 vs. 5.7 ± 0.7 months, P = 0.001), and the median overall survival period in the BDC group was prone to significant difference than that in the CDC group (9.4 ± 4.0 vs. 8.2 ± 0.3 months, P = 0.089).ConclusionThe findings of this study show that BDC with chemotherapy was associated with better stent patency and survival. However, since the sample size was very small, large randomized controlled multicenter studies are needed to further evaluate the long-term survival effects of BDC in patients with advanced pancreatic carcinoma combined with obstructive jaundice.

Is irreversible electroporation (IRE) an effective and safe ablation method for local advanced pancreatic cancer: A meta-analysis

To evaluate the safety and efficacy of irreversible electroporation (IRE) for treating local advanced pancreatic carcinoma. Relevant literature published from January 1, 2010, to July 1, 2021, was retrieved from PubMed and EMBASE databases. The following keywords were applied: " IRE, "Irreversible electrophoresis, "pancreatic cancer, "ablation, "and " ablation therapy. "The primary outcomes was IRE related significant complications rate. 19 studies were included, a total of 984 patients had undergone IRE. The probability of IRE-related major (Grade 3–5) complications rate was 17% (95% CI: 10–28%). 2 deaths related to IRE procedure were reported. The median overall survival time since IRE ranged from 6.1 to 27 months. Patients treated with IRE combined with surgical resection or standard chemotherapy showed a longer overall survival. IRE can benefit the survival of patients with locally advanced pancreatic cancer, but related adverse events should be treated with caution.

High-intensity focused ultrasound (HIFU) therapy for pain palliation in advanced stage pancreatic carcinoma: A Meta-Analysis with recent studies

Background: Day by day, High-intensity focused ultrasound (HIFU) therapy is becoming more familiar in medical field because it is non-invasive technique with fewer side effects and provides promising therapeutic results. Several HIFU therapy applications have approved by many approval authorities of deferent countries since last decade. It is a novel, emerging, therapeutic modality that uses ultrasound waves, propagated through tissue media, as carriers of energy. HIFU has great potential for tumor ablation and the main mechanisms of HIFU ablation involve mechanical and thermal effects. Pancreatic adenocarcinoma is currently the fourth-leading cause of cancer-related death. Up to 60–90% of patients with advanced disease suffer cancer-related pain, severely impacting their quality of life. Current management involves primarily pharmacotherapy with opioid narcotics and celiac plexus neurolysis; unfortunately, both approaches offer transient relief and cause undesired side-effects. High intensity focused ultrasound (HIFU) is a non-invasive thermal ablation technique that has been used to treat pancreatic cancer. This meta-analysis aims to evaluate the role of HIFU in pain palliation of advanced unresectable pancreatic adenocarcinoma. Methods: Paper selection was performed electronically in PubMed up to the end of March 2021, for pain palliation treatment of advanced staged pancreatic cancer with HIFU. Relevant papers were identified through the PubMed search engine using these keywords: HIFU, pancreas, pancreatic cancer, pain and palliation. Additional studies were also done included after manual search of the selected bibliographies. Palliation results reported in studies were analyzed using a logit-transformed random-effects model using the inverse variance method, with the DerSimonian-Laird estimator for t2, and Cochran’s Q test for heterogeneity among studies. The I2 was also calculated to assess the percentage of the total variability in the different effect size estimates that can be attributed to heterogeneity among the true effects and rank correlation test of funnel plot asymmetry was done to assess possible publication bias. Results: In this meta-analysis, we includes only recent 10 year studies i.e. total number of 16 studies with 687total patients with pancreatic cancer. The total patients enrolled ranges from 7 patients in the smallest series, up to 120 in the largest study. The calculated τ2was 0.187, and I2was 41%, the Q test p-value was 0. 026, is indicating significant heterogeneity among studies. The random effects estimate of the proportion of patients with pain reduction was 0.89.08. Conclusions: We concluded that HIFU performs to be an effective tool for pain palliation in advanced staged pancreatic cancer. Prospective randomized and standardized studies are necessary to confirm the effectiveness of HIFU in relieving pain, and to evaluate for any potential impact on tumor control and patient survival.

Hyperbaric oxygen regulates tumor mechanics and augments Abraxane and gemcitabine antitumor effects against pancreatic ductal adenocarcinoma by inhibiting cancer-associated fibroblasts

While the combination of Abraxane and gemcitabine (GEM) has been approved as a first-line therapy for the treatment of advanced pancreatic ductal carcinoma (PDAC), the clinical antitumor efficacy is dismal thus far. Here, we explore hyperbaric oxygen (HBO) therapy to boost antitumor efficacy of Abraxane and GEM against murine PDAC Panc02 tumors. Mechanistically, we reveal that HBO significantly constrains cancer-associated fibroblasts (CAFs) by disrupting hypoxia. As CAFs are the main producers of extracellular matrix (ECM) components, HBO effectively reduces collagen Ⅰ and fibronectin, leading to normalization of not only tumor mechanics but also blood vessels. Therefore, HBO augments drug delivery in terms of tumor accumulation, penetration, and cellular internalization. Furthermore, we demonstrate that HBO helps Abraxane and GEM eliminate cancer stem cells (CSCs) by regulating CAFs mediated CSCs niche. Consequently, HBO potentiates antitumor efficacy of Abraxane and GEM by inhibiting not only primary tumors but more importantly metastases of Panc02 tumors, with negligible side effects. Given HBO, Abraxane, and GEM are routinely applied in clinical practice, their combination is readily translatable to bedside applications.