Search

Abstract Background Gastrojejunostomy (GJJ) is the most commonly used palliative treatment modality for malignant gastric outlet obstruction. Recently, stent placement has been introduced as an alternative treatment. We reviewed the available literature on stent placement and GJJ for gastric outlet obstruction, with regard to medical effects and costs. Methods A systematic review of the literature was performed by searching PubMed for the period January 1996 and January 2006. A total of 44 publications on GJJ and stents was identified and reported results on medical effects and costs were pooled and evaluated. Results from randomized and comparative studies were used for calculating odds ratios (OR) to compare differences between the two treatment modalities. Results In 2 randomized trials, stent placement was compared with GJJ (with 27 and 18 patients in each trial). In 6 comparative studies, stent placement was compared with GJJ. Thirty-six series evaluated either stent placement or GJJ. A total of 1046 patients received a duodenal stent and 297 patients underwent GJJ. No differences between stent placement and gastrojejunostomy were found in technical success (96% vs. 100%), early and late major complications 7% vs. 6% and 18% vs. 17%, respectively) and persisting symptoms (8% vs. 9%). Initial clinical success was higher after stent placement (89% vs. 72%). Minor complications were less frequently seen after stent placement in the patient series (9% vs. 33%), however the pooled analysis showed no differences (OR: 0.75, p = 0.8). Recurrent obstructive symptoms were more common after stent placement (18% vs. 1%). Hospital stay was prolonged after GJJ compared to stent placement (13 days vs. 7 days). The mean survival was 105 days after stent placement and 164 days after GJJ. Conclusion These results suggest that stent placement may be associated with more favorable results in patients with a relatively short life expectancy, while GJJ is preferable in patients with a more prolonged prognosis. The paucity of evidence from large randomized trials may however have influenced the results and therefore a trial of sufficient size is needed to determine which palliative treatment modality is optimal in (sub)groups of patients with malignant gastric outlet obstruction.

Abstract Background Surgery in patients with obstructive jaundice caused by a periampullary (pancreas, papilla, distal bile duct) tumor is associated with a higher risk of postoperative complications than in non-jaundiced patients. Preoperative biliary drainage was introduced in an attempt to improve the general condition and thus reduce postoperative morbidity and mortality. Early studies showed a reduction in morbidity. However, more recently the focus has shifted towards the negative effects of drainage, such as an increase of infectious complications. Whether biliary drainage should always be performed in jaundiced patients remains controversial. The randomized controlled multicenter DROP-trial (DRainage vs. Operation) was conceived to compare the outcome of a 'preoperative biliary drainage strategy' (standard strategy) with that of an 'early-surgery' strategy, with respect to the incidence of severe complications (primary-outcome measure), hospital stay, number of invasive diagnostic tests, costs, and quality of life. Methods/design Patients with obstructive jaundice due to a periampullary tumor, eligible for exploration after staging with CT scan, and scheduled to undergo a "curative" resection, will be randomized to either "early surgical treatment" (within one week) or "preoperative biliary drainage" (for 4 weeks) and subsequent surgical treatment (standard treatment). Primary outcome measure is the percentage of severe complications up to 90 days after surgery. The sample size calculation is based on the equivalence design for the primary outcome measure. If equivalence is found, the comparison of the secondary outcomes will be essential in selecting the preferred strategy. Based on a 40% complication rate for early surgical treatment and 48% for preoperative drainage, equivalence is taken to be demonstrated if the percentage of severe complications with early surgical treatment is not more than 10% higher compared to standard treatment: preoperative biliary drainage. Accounting for a 10% dropout, 105 patients are needed in each arm resulting in a study population of 210 (alpha = 0.95, beta = 0.8). Discussion The DROP-trial is a randomized controlled multicenter trial that will provide evidence whether or not preoperative biliary drainage is to be performed in patients with obstructive jaundice due to a periampullary tumor.

Abstract Background The initial treatment of acute necrotizing pancreatitis is conservative. Intervention is indicated in patients with (suspected) infected necrotizing pancreatitis. In the Netherlands, the standard intervention is necrosectomy by laparotomy followed by continuous postoperative lavage (CPL). In recent years several minimally invasive strategies have been introduced. So far, these strategies have never been compared in a randomised controlled trial. The PANTER study (PAncreatitis, Necrosectomy versus sTEp up appRoach) was conceived to yield the evidence needed for a considered policy decision. Methods/design 88 patients with (suspected) infected necrotizing pancreatitis will be randomly allocated to either group A) minimally invasive 'step-up approach' starting with drainage followed, if necessary, by videoscopic assisted retroperitoneal debridement (VARD) or group B) maximal necrosectomy by laparotomy. Both procedures are followed by CPL. Patients will be recruited from 20 hospitals, including all Dutch university medical centres, over a 3-year period. The primary endpoint is the proportion of patients suffering from postoperative major morbidity and mortality. Secondary endpoints are complications, new onset sepsis, length of hospital and intensive care stay, quality of life and total (direct and indirect) costs. To demonstrate that the 'step-up approach' can reduce the major morbidity and mortality rate from 45 to 16%, with 80% power at 5% alpha, a total sample size of 88 patients was calculated. Discussion The PANTER-study is a randomised controlled trial that will provide evidence on the merits of a minimally invasive 'step-up approach' in patients with (suspected) infected necrotizing pancreatitis.

Background: Gastrojejunostomy (GJJ) is the most commonly used palliative treatment modality for malignant gastric outlet obstruction. Recently, stent placement has been introduced as an alternative treatment. We reviewed the available literature on stent placement and GJJ for gastric outlet obstruction, with regard to medical effects and costs. Methods: A systematic review of the literature was performed by searching PubMed for the period January 1996 and January 2006. A total of 44 publications on GJJ and stents was identified and reported results on medical effects and costs were pooled and evaluated. Results from randomized and comparative studies were used for calculating odds ratios (OR) to compare differences between the two treatment modalities. Results: In 2 randomized trials, stent placement was compared with GJJ (with 27 and 18 patients in each trial). In 6 comparative studies, stent placement was compared with GJJ. Thirty-six series evaluated either stent placement or GJJ. A total of 1046 patient received a duodenal stent and 297 patients underwent GJJ. No differences between stent placement and gastrojejunostomy were found in technical success (96% vs. 100%), early and late major complications 7% vs. 6% and 18% vs. 17%, respectively) and persisting symptoms (8% vs. 9%). Initial clinical success was higher after stent placement (89% vs. 72%). Minor complications were less frequently seen after stent placement in the patient series (9% vs. 33%), however the pooled analysis showed no differences (OR: 0.75, p = 0.8). Recurrent obstructive symptoms were more common after stent placement (18% vs. 1%). Hospital stay was prolonged after GJJ compared to stent placement (13 days vs. 7 days). The mean survival was 105 days after stent placement and 164 days after GJJ. Conclusion: These results suggest that stent placement may be associated with more favorable results in patients with a relatively short life expectancy, while GJJ is preferable in patients with a more prolonged prognosis. The paucity of evid ence from large randomized trials may however have influenced the results and therefore a trial of sufficient size is needed to determine which palliative treatment modality is optimal in (sub)groups of patients with malignant gastric outlet obstruction. [ABSTRACT FROM AUTHOR]

Background: Liver surgery in perihilar cholangiocarcinoma (PHC) is associated with high postoperative morbidity because the tumor typically causes biliary obstruction. Preoperative biliary drainage is used to create a safer environment prior to liver surgery, but biliary drainage may be harmful when severe drainage-related complications deteriorate the patients' condition or increase the risk of postoperative morbidity. Biliary drainage can cause cholangitis/cholecystitis, pancreatitis, hemorrhage, portal vein thrombosis, bowel wall perforation, or dehydration. Two methods of preoperative biliary drainage are mostly applied: endoscopic biliary drainage, which is currently used in most regional centers before referring patients for surgical treatment, and percutaneous transhepatic biliary drainage. Both methods are associated with severe drainage-related complications, but two small retrospective series found a lower incidence in the number of preoperative complications after percutaneous drainage compared to endoscopic drainage (18-25% versus 38-60%, respectively). The present study randomizes patients with potentially resectable PHC and biliary obstruction between preoperative endoscopic or percutaneous transhepatic biliary drainage.Methods/design: The study is a multi-center trial with an "all-comers" design, randomizing patients between endoscopic or percutaneous transhepatic biliary drainage. All patients selected to potentially undergo a major liver resection for presumed PHC are eligible for inclusion in the study provided that the biliary system in the future liver remnant is obstructed (even if they underwent previous inadequate endoscopic drainage). Primary outcome measure is the total number of severe preoperative complications between randomization and exploratory laparotomy. The study is designed to detect superiority of percutaneous drainage: a provisional sample size of 106 patients is required to detect a relative decrease of 50% in the number of severe preoperative complications (alpha = 0.95; beta = 0.8). Interim analysis after inclusion of 53 patients (50%) will provide the definitive sample size. Secondary outcome measures encompass the success of biliary drainage, quality of life, and postoperative morbidity and mortality.Discussion: The DRAINAGE trial is designed to identify a difference in the number of severe drainage-related complications after endoscopic and percutaneous transhepatic biliary drainage in patients selected to undergo a major liver resection for perihilar cholangiocarcinoma.Trial Registration: Netherlands Trial Register [ NTR4243 , 11 October 2013]. [ABSTRACT FROM AUTHOR]

Pancreatic cancer has a dismal prognosis, and treatment options for patients with locally advanced or metastatic disease are limited. Early tumor progression after standard chemo- and or radiotherapy remains a major concern in managing these patients. Treating pancreatic cancer patients with the Toll-like receptor 3 (TLR-3) agonist rintatolimod (Ampligen ® ) was effective in boosting the immune response. Rintatolimod acts via the TLR-3 receptor on several immune cells. However, the TLR-3 expression pattern in pancreatic cancer cells and how rintatolimod affects pancreatic cancer cells have not yet been investigated. The TLR-3 protein and mRNA expression were evaluated in thirteen PDAC tissue samples as well as in the human PDAC (hPDAC) cell lines CFPAC-1, MIAPaCa-2, and PANC-1 using immunohistochemistry and multiplexed gene expression analysis, respectively. The direct anti-tumor effects of rintatolimod were investigated using a proliferation and migration assay after different incubation time points with increasing concentrations of rintatolimod (ranging from 0.05 to 0.4 mg/ml). The TLR-3 protein and mRNA expression were heterogeneous between the PDAC tissue samples and the three hPDAC cell lines. TLR-3 protein and mRNA expression were high in CFPAC-1, moderate in MIAPaCa-2, and undetectable in PANC-1. Rintatolimod three-day treatment resulted in significantly reduced proliferation of CFPAC-1 cells compared to vehicle-treated control cells. In addition, after 24 hours, rintatolimod-treated CFPAC-1 cells showed less cell migration compared to vehicle-treated control cells, although this difference was not statistically significant. Lastly, we identified fifteen genes, altered with a Log 2 FOC > |1.0| in rintatolimod-treated CFPAC-1 cells, which were significantly related to three transcription factors (NFKB1, RELA, and SP1) regulating the TLR-3 signaling pathway. In conclusion, we propose that rintatolimod treatment might have a direct TLR-3-dependent anti-tumoral effect on pancreatic cancer cells expressing TLR-3., Competing Interests: None., (AJCR Copyright © 2023.)

Objective: Lumen-apposing metal stents (LAMS) are believed to clinically improve endoscopic transluminal drainage of infected necrosis when compared with double-pigtail plastic stents. However, comparative data from prospective studies are very limited., Design: Patients with infected necrotising pancreatitis, who underwent an endoscopic step-up approach with LAMS within a multicentre prospective cohort study were compared with the data of 51 patients in the randomised TENSION trial who had been assigned to the endoscopic step-up approach with double-pigtail plastic stents. The clinical study protocol was otherwise identical for both groups. Primary end point was the need for endoscopic transluminal necrosectomy. Secondary end points included mortality, major complications, hospital stay and healthcare costs., Results: A total of 53 patients were treated with LAMS in 16 hospitals during 27 months. The need for endoscopic transluminal necrosectomy was 64% (n=34) and was not different from the previous trial using plastic stents (53%, n=27)), also after correction for baseline characteristics (OR 1.21 (95% CI 0.45 to 3.23)). Secondary end points did not differ between groups either, which also included bleeding requiring intervention-5 patients (9%) after LAMS placement vs 11 patients (22%) after placement of plastic stents (relative risk 0.44; 95% CI 0.16 to 1.17). Total healthcare costs were also comparable (mean difference -€6348, bias-corrected and accelerated 95% CI -€26 386 to €10 121)., Conclusion: Our comparison of two patient groups from two multicentre prospective studies with a similar design suggests that LAMS do not reduce the need for endoscopic transluminal necrosectomy when compared with double-pigtail plastic stents in patients with infected necrotising pancreatitis. Also, the rate of bleeding complications was comparable., Competing Interests: Competing interests: MGB reports grants from Intuitive, grants from Ethicon Endo-Surgery, grants from Medtronic, outside the submitted work; MBo reports grants and personal fees from Johnson & Johnson, grants and personal fees from Acelity/KCI, grants and personal fees from Bard, grants from Ipsen, grants from New Compliance, grants from Mylan, personal fees from Gore, personal fees from Smith & Newphew, outside the submitted work; MBr reports grants and personal fees from Boston Scientific, grants and personal fees from Cook Medical, grants from Pentax Medical, grants from Mylan, grants from 3M, grants from InterScope, outside the submitted work; PF reports personal fees from Cook Medical, personal fees from Olympus, personal fees from Ethicon Endo-Surgery, outside the submitted work; J-WP reports personal fees and other from Cook Endoscopy, personal fees and other from Boston Scientific, personal fees and other from Pentax Medical, outside the submitted work; E-JvG reports grants from Mylan, grants from Olympus, personal fees from MTW-Endoskopie, outside the submitted work; JEvH reports personal fees from Olympus Endoscopy, grants from Cook Medical, personal fees from Boston Scientific, personal fees from Medtronic, outside the submitted work; FV reports grants from Boston Scientific, outside the submitted work; RPV reports grants and personal fees from Boston Scientific, grants from Zambon, outside the submitted work., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Little is known about the microcirculatory alterations in patients with chronic mesenteric ischemia (CMI). We hypothesized that patients with CMI have an impaired microcirculatory function and show an oral microcirculatory response after caloric challenge compared to healthy controls., Methods: All patients and controls received the standard workup for CMI. Sublingual micro-circulation was evaluated before (T0) and 20 minutes after (T1) feeding. The total vessel density (TVD; mm/mm 2 ), perfused vessel density (PVD; mm/mm 2 ), proportion of perfused vessels (PPV; %) and microvascular flow index (MFI; AU) were assessed., Results: We included 12 patients (63.2 years [IQR 48.8-70.4 years], 67% males) and 12 controls (32.7 years [IQR 27.7-38.1 years], 42% males). At baseline, patients with CMI had a decreased PPV of the sublingual small vessels (median 84.8% vs 95.7%, P =0.006), PPV of all vessels (PPV median 85.4% vs 95.3%, P =0.007) and microvascular flow index of all vessels (MFIa; median 3.00 vs 2.80, P =0.039) compared to healthy controls. After caloric challenge, PVD increased significantly in both small vessels (perfused vessel density of the small vessels [PVDs]) and all vessels (perfused vessel density of all vessels [PVDa]; PVDs [T0]) median 16.3 [IQR 13.3-22.1] vs [T1] median 19.9 [IQR 14.2-26.2], P =0.008; PVDa [T0] median 19.1 [IQR 16.2-23.6] vs [T1] median 22.2 [IQR 16.5-28.9], P =0.02; proportion of perfused vessels of the small vessels (PPVs; [T0] median 84.8% [IQR 75.3-90.4] vs [T1] median 91.0% [IQR 80.1-93.8], P =0.010). In contrast, no significant changes in microcirculatory parameters were observed after caloric challenge in healthy controls., Conclusion: Patients with CMI have an impaired sublingual microcirculation at baseline and show a significant response in the sublingual microcirculation after caloric challenge, whereas healthy controls have a normal microcirculation at baseline and show no reactive response upon a caloric challenge as seen in CMI patients. Sublingual microcirculation visualization may offer a rapid noninvasive method to identify patients at risk for having CMI., Competing Interests: Disclosure Professor Ince has developed stream dark field imaging, the predecessor of the device used in this study, and is listed as an inventor on related patents commercialized by MicroVision Medical (MVM) under a license from the Academic Medical Center in Amsterdam, the Netherlands. He has been a consultant for MVM in the past but has not been involved with this company for >5 years now and holds no shares. Braedius Medical, a company owned by a relative of Professor Ince, has developed and designed a handheld microscope called CytoCam-IDF imaging used in this study. Professor Ince has no financial relation with Braedius Medical of any sort, ie, never owned shares, or received consultancy or speaker fees from Braedius Medical. The authors report no other conflicts of interest in this work.

Collecting repeat samples of blood ("liquid biopsies") is a broadly used clinical approach for serial monitoring of disease or response to treatments. In patients with cancer the most distinct molecular feature are somatic mutations acquired by cancer cells present in the diseased tissue. Indeed, mutant DNA derived from dying or lysed cancer cells can be isolated from patient serum samples, subjected to DNA sequencing and to analysis of abundance as a measure of tumor burden. Also, changes in the DNA mutation patterns in serum samples collected over time can indicate altered pathways or clonal evolution of the disease and altered abundance of mutant DNA suggests an altered disease burden. In addition, during the course of treatment, changes in circulating DNA mutation patterns can indicate the emergence of resistant clones and prompt changes in treatment. In contrast to mutant DNA, microRNAs (miR) are transcribed, processed, packaged and released from cells in normal and in diseased tissues as part of the extracellular crosstalk between cells. Interestingly, released miR can function in cell-to-cell communication and as hormone-like signals that operate at a distance through their release into the circulation and subsequent uptake into cells in distant tissues. Circulating miR expression patterns can be established from serial serum samples and monitored for alterations over time. Circulating miR provide a readout of the organism's steady state and serial analyses will indicate changes in the response to therapy or an altered physiologic or disease state. Furthermore, changes in circulating miR patterns can indicate treatment efficacy or resistance as well as adverse effects associated with the respective intervention. Thus, the combined serial analysis of mutant DNA and miR in the circulation has the potential to provide a molecular footprint of pancreatic cancer and can be used to monitor treatment responses or resistance to treatment in real time with a minimally invasive procedure.

Introduction: Pancreatic cancer is a highly aggressive malignancy with few treatment options. The overexpression of several growth factors, including insulin and insulin-like growth factors (IGFs), can underlie the aggressive nature of this disease. Previous research has demonstrated potent effects of interferon (IFN)-β on pancreatic cancer cell growth, however up till now it is unknown whether IFN-β is able to counteract IGF1, IGF2 and insulin-induced pancreatic cancer cell proliferation and migration., Methods: Expression of IGF- and insulin receptors was determined and the stimulatory effects of IGF1, IGF2 and insulin on cell proliferation and migration, as well as the inhibitory effects of IFN-β were evaluated in 3 human pancreatic adenocarcinoma cell lines., Results: Both the insulin- and the IGF1 receptor were variably expressed in the cell lines. IGF1, IGF2 and insulin were capable of stimulating cell proliferation in all three cell lines, however cell migration was significantly enhanced only in the BxPC-3 cell line. IFN-β significantly inhibited IGF1-, IGF2- and insulin-stimulated proliferation in all three cell lines in a dose and time dependent manner. Furthermore, in the BxPC-3 cell line IFN-β significantly inhibited both basal and IGF1-, IGF2- and insulin-stimulated cell migration., Conclusion: Both IGF1, -2 and insulin were capable of stimulating proliferation and migration in human pancreatic cancer cells irrespective of the type of receptor expressed. This study demonstrates that insulin, in addition to IGF1 and IGF2, may play an important role in the progression of pancreatic cancer. Moreover, IFN-β strongly inhibits growth factor stimulated cell proliferation and migration. Our study supports previous findings which have suggested that IFN-β can be a potential promising anti-cancer agent in pancreatic cancer.