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Journal of Gastrointestinal Oncology Apr 2024While surufatinib, sunitinib, and everolimus have shown efficacy for advanced neuroendocrine neoplasms (NENs) in randomized controlled trials (RCTs), direct comparisons...
Assessing the effectiveness and safety of surufatinib versus everolimus or sunitinib in advanced neuroendocrine neoplasms: insights from a real-world, retrospective cohort study using propensity score and inverse probability treatment weighting analysis.
BACKGROUND
While surufatinib, sunitinib, and everolimus have shown efficacy for advanced neuroendocrine neoplasms (NENs) in randomized controlled trials (RCTs), direct comparisons in a real-world setting remain unexplored. This gap highlights the clinical need to understand their comparative effectiveness and safety within the diverse Chinese population. Addressing this, our study provides insights into the real-world performance of these therapies, aiming to inform treatment selection and improve patient outcomes.
METHODS
A retrospective, observational study was conducted at Fudan University Shanghai Cancer Center, including patients with advanced NENs treated with surufatinib, sunitinib, or everolimus between July 2020 and April 2023. Eligibility criteria focused on histologically confirmed, locally advanced, unresectable, or metastatic NENs, with patients having received at least one month of targeted therapy. We employed inverse probability weighting (IPW) with the propensity score (PS) matching to adjust for the bias of baseline characteristics. The assessment of covariates included age, sex, performance status, primary tumor site, functional status, genetic mutations, tumor differentiation, Ki67 index, tumor grade, metastasis site, and previous therapies. The primary outcome was progression-free survival (PFS), and secondary outcomes included objective response rate (ORR), disease control rate (DCR), and adverse events (AEs).
RESULTS
The study enrolled 123, 56, and 68 locally advanced or metastatic NEN patients treated with surufatinib, sunitinib, and everolimus, respectively. Before adjusting for confounding factors, surufatinib was used less frequently as a first-line treatment compared to sunitinib and everolimus in pancreatic NENs (pNENs) (11.1% 22.1%, P=0.057). Significant differences were noted in prior treatments and tumor characteristics between surufatinib and everolimus groups in extrapancreatic NENs (epNENs) (P<0.05). Post-IPW, these disparities were resolved (P>0.05). Surufatinib demonstrated superior median PFS (mPFS) in both pancreatic [8.30 6.33 months, hazard ratio (HR) 0.592, P<0.001] and epNENs (8.73 3.70 months, HR 0.608, P<0.001) compared to everolimus or sunitinib. Notably, male gender (HR 1.75, P=0.001), functional status (HR 2.09, P=0.01), Ki67 index >20% (HR 12.7, P=0.004), previous somatostatin analogue (SSA) treatment (HR 1.73, P=0.001), germline mutation (HR 5.62, P<0.001), poor differentiation (HR 7.45, P<0.001), liver metastasis (HR 1.72, P=0.001) and multiple treatment lines (HR 1.62 for 2 line, P=0.04; HR 1.88 for ≥3 line, P=0.01) were identified as negative prognostic factors for PFS. Conversely, dose adjustment (HR 0.63, P=0.009) and treatment with surufatinib (HR 0.58 for pNEN, P<0.001; HR 0.62 for epNEN, P=0.002) were correlated with longer PFS.
CONCLUSIONS
In a real-world Chinese cohort, surufatinib significantly outperformed sunitinib and everolimus in prolonging PFS among advanced NEN patients, with identifiable clinical features impacting survival, and conclusions regarding superiority should be interpreted with caution due to the retrospective design. Our findings underscore the need for prospective studies to further validate these results and explore additional predictive biomarkers for personalized treatment strategies.
PubMed: 38756630
DOI: 10.21037/jgo-24-218 -
JPGN Reports May 2024Herbal and dietary supplements (HDS) are a common etiology of drug induced liver injury and, specifically, Herbalife® supplements have been implicated. Hepatitis...
Herbal and dietary supplements (HDS) are a common etiology of drug induced liver injury and, specifically, Herbalife® supplements have been implicated. Hepatitis associated aplastic anemia (HAAA) is a rare and potentially fatal complication after acute hepatitis characterized by pancytopenia. While there have been rare cases of HDS leading to HAAA, no cases of Herbalife® induced liver injury leading to HAAA have been reported from this specific HDS. We report a unique case of severe aplastic anemia developing after sub-fulminant liver failure associated with chronic HDS use. This case illustrates the importance of warning the public about HDS as their use continues to increase. It is not only important to recognize HDS as etiology, but also for healthcare providers to carefully monitor these patients after resolution of liver injury for the development of HAAA.
PubMed: 38756121
DOI: 10.1002/jpr3.12041 -
JPGN Reports May 2024Stone formation in a gallbladder remnant is a rare postcholecystectomy complication. This report describes the case of gallstones in a gallbladder remnant of an...
Stone formation in a gallbladder remnant is a rare postcholecystectomy complication. This report describes the case of gallstones in a gallbladder remnant of an adolescent with sickle cell disease (SCD) years after laparoscopic cholecystectomy. A 15-year-old female with SCD presented to our gastroenterology clinic with concerns of recurrent choledocholithiasis despite cholecystectomy 2 years before presentation. About 4 months before presentation to our clinic, she was evaluated at the referring physician's emergency department for recurrent severe abdominal pain of 1 month duration. After admission to the hospital, common bile duct stones were seen on magnetic resonance cholangiopancreatography (MCRP) imaging and subsequently removed via endoscopic retrograde cholangiopancreatography (ERCP). On review of her MRCP and ERCP at our hospital, a remnant of gallbladder containing multiple stones was identified. She subsequently underwent a laparoscopic resection of the gallbladder remnant. Clinicians should consider biliary duct imaging in children with biliary colic following cholecystectomy, especially those with history of chronic hemolysis.
PubMed: 38756117
DOI: 10.1002/jpr3.12039 -
Clinical Endoscopy May 2024Postoperative pancreatic fistulas (POPFs) are common adverse events that occur after pancreatic surgery. Endoscopic ultrasonography (EUS)-guided drainage (EUS-D) is a... (Review)
Review
Postoperative pancreatic fistulas (POPFs) are common adverse events that occur after pancreatic surgery. Endoscopic ultrasonography (EUS)-guided drainage (EUS-D) is a first-line treatment, similar to that for pancreatic fluid collection (PFCs) after acute pancreatitis. However, some POPFs do not develop fluid collections depending on the presence or location of the surgical drain, whereas others develop fluid collections, such as postoperative fluid collections (POPFCs). Although POPFCs are similar to PFCs, the strategy and modality for POPF management need to be modified according to the presence of fluid collections, surgical drains, and surgical type. As discussed for PFCs, the indications, timing, and selection of interventions or stents for EUS-D have not been fully elucidated for POPFs. In this review, we discuss the management of POPFs and POPFCs in comparison with PFCs due to acute pancreatitis and summarize the topics that should be addressed in future studies.
PubMed: 38756067
DOI: 10.5946/ce.2023.254 -
Clinical Endoscopy May 2024Endoscopic biliary drainage using self-expandable metallic stents (SEMSs) for malignant biliary strictures occasionally induces acute cholecystitis (AC). This study...
Prophylactic endoscopic transpapillary gallbladder stenting to prevent acute cholecystitis induced after metallic stent placement for malignant biliary strictures: a retrospective study and Japan.
BACKGROUND/AIMS
Endoscopic biliary drainage using self-expandable metallic stents (SEMSs) for malignant biliary strictures occasionally induces acute cholecystitis (AC). This study evaluated the efficacy of prophylactic gallbladder stents (GBS) during SEMS placement.
METHODS
Among 158 patients who underwent SEMS placement for malignant biliary strictures between January 2018 and March 2023, 30 patients who attempted to undergo prophylactic GBS placement before SEMS placement were included.
RESULTS
Technical success was achieved in 21 cases (70.0%). The mean diameter of the cystic duct was more significant in the successful cases (6.5 mm vs. 3.7 mm, p<0.05). Adverse events occurred for 7 patients (23.3%: acute pancreatitis in 7; non-obstructive cholangitis in 1; perforation of the cystic duct in 1 with an overlap), all of which improved with conservative treatment. No patients developed AC when the GBS placement was successful, whereas 25 of the 128 patients (19.5%) without a prophylactic GBS developed AC during the median follow-up period of 357 days (p=0.043). In the multivariable analysis, GBS placement was a significant factor in preventing AC (hazard ratio, 0.61; 95% confidence interval, 0.37-0.99; p=0.045).
CONCLUSIONS
GBS may contribute to the prevention of AC after SEMS placement for malignant biliary strictures.
PubMed: 38756066
DOI: 10.5946/ce.2023.284 -
Zhong Nan Da Xue Xue Bao. Yi Xue Ban =... Feb 2024Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease that is prevalent in middle-aged and elderly women, characterized by dry mouth, dry eyes, fatigue, and... (Review)
Review
Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease that is prevalent in middle-aged and elderly women, characterized by dry mouth, dry eyes, fatigue, and joint pain. Nearly one-third pSS patients have been suffering with osteoporosis (OP), displaying symptoms of lumbago, back pain, and even fracture, all of which severely affect their life quality. Common risk factors for pSS and OP include gender and age, persistent state of inflammation, immune disorders, intestinal flora imbalance, vitamin D deficiency, dyslipidemia and sarcopenia. Meanwhile, the comorbidities of pSS, such as renal tubular acidosis, primary biliary cholangitis, autoimmune thyroid diseases, and drugs (glucocorticoids, methotrexate, and cyclophosphamide) are unique risk factors for pSS complicated with OP. Education, guidance of healthy lifestyle, and OP screening are recommended for bone management of pSS patients. Early detection and intervention are crucial for keeping bone health and life quality in pSS patients.
Topics: Humans; Sjogren's Syndrome; Osteoporosis; Risk Factors; Female; Comorbidity; Vitamin D Deficiency; Quality of Life
PubMed: 38755728
DOI: 10.11817/j.issn.1672-7347.2024.230295 -
BMC Cancer May 2024With the increasing of novel therapeutics for the treatment of Biliary Tract Cancers (BTC), and the need to assess their socio-economic impacts for national licence...
BACKGROUND
With the increasing of novel therapeutics for the treatment of Biliary Tract Cancers (BTC), and the need to assess their socio-economic impacts for national licence approvals, it is as important as ever to have real-life data in national populations.
METHODS AND RESULTS
We performed an audit of the first 2 year-activity (Sep 2019-Sep 2021) of the centralized West-of-Scotland-BTC clinic. 122 patients accessed the service, including 68% with cholangiocarcinoma (CCA), 27% with gallbladder cancer (GBC), and 5% with ampulla of Vater carcinoma with biliary phenotype (AVC). Median age at diagnosis was 66 (28-84), with 30% of newly diagnosed patients being younger than 60 years-old. Thirty-five cases (29%) underwent surgery, followed by adjuvant-chemotherapy in 66%. 60% had recurrent disease (80% with distant relapse). Sixty-four patients (58%) started first-line Systemic-AntiCancer-Treatment (SACT). Of these, 37% received second line SACT, the majority of which had iCCA and GBC. Thirty-% of those who progressed received third line SACT.
CONCLUSIONS
About 30% of BTC were eligible for curative surgery. Fifty-eight and twenty% of the overall cohort of advanced BTC patients received first and second line SACT. Our data suggest that reflex genomic profiling may not be cost-effective until molecularly driven strategies are limited to second line setting.
Topics: Humans; Middle Aged; Female; Male; Aged; Adult; Scotland; Aged, 80 and over; Biliary Tract Neoplasms; Cholangiocarcinoma; Gallbladder Neoplasms; Chemotherapy, Adjuvant
PubMed: 38755562
DOI: 10.1186/s12885-024-12279-6 -
NAR Cancer Jun 2024DNA methylation is a pivotal epigenetic modification that defines cellular identity. While cell deconvolution utilizing this information is considered useful for...
DNA methylation is a pivotal epigenetic modification that defines cellular identity. While cell deconvolution utilizing this information is considered useful for clinical practice, current methods for deconvolution are limited in their accuracy and resolution. In this study, we collected DNA methylation data from 945 human samples derived from various tissues and tumor-infiltrating immune cells and trained a neural network model with them. The model, termed MEnet, predicted abundance of cell population together with the detailed immune cell status from bulk DNA methylation data, and showed consistency to those of flow cytometry and histochemistry. MEnet was superior to the existing methods in the accuracy, speed, and detectable cell diversity, and could be applicable for peripheral blood, tumors, cell-free DNA, and formalin-fixed paraffin-embedded sections. Furthermore, by applying MEnet to 72 intrahepatic cholangiocarcinoma samples, we identified immune cell profiles associated with cancer prognosis. We believe that cell deconvolution by MEnet has the potential for use in clinical settings.
PubMed: 38751935
DOI: 10.1093/narcan/zcae022 -
Transplant International : Official... 2024Due to its intrinsic complexity and the principle of collective solidarity that governs it, solid organ transplantation (SOT) seems to have been spared from the increase...
Due to its intrinsic complexity and the principle of collective solidarity that governs it, solid organ transplantation (SOT) seems to have been spared from the increase in litigation related to medical activity. Litigation relating to solid organ transplantation that took place in the 29 units of the Assistance Publique-Hôpitaux de Paris and was the subject of a judicial decision between 2015 and 2022 was studied. A total of 52 cases of SOT were recorded, all in adults, representing 1.1% of all cases and increasing from 0.71% to 1.5% over 7 years. The organs transplanted were 25 kidneys (48%), 19 livers (37%), 5 hearts (9%) and 3 lungs (6%). For kidney transplants, 11 complaints (44%) were related to living donor procedures and 6 to donors. The main causes of complaints were early post-operative complications in 31 cases (60%) and late complications in 13 cases (25%). The verdicts were in favour of the institution in 41 cases (79%). Solid organ transplants are increasingly the subject of litigation. Although the medical institution was not held liable in almost 80% of cases, this study makes a strong case for patients, living donors and their relatives to be better informed about SOT.
Topics: Humans; Organ Transplantation; Hospitals, University; Adult; Male; Female; Postoperative Complications; Living Donors; Middle Aged; Liver Transplantation; Kidney Transplantation; Europe; Lung Transplantation
PubMed: 38751770
DOI: 10.3389/ti.2024.12439 -
Liver Cancer Apr 2024Lenvatinib is indicated for the forefront treatment of advanced hepatocellular carcinoma (aHCC), but its use may be limited by the risk of esophagogastric varices (EGV)...
INTRODUCTION
Lenvatinib is indicated for the forefront treatment of advanced hepatocellular carcinoma (aHCC), but its use may be limited by the risk of esophagogastric varices (EGV) bleeding. This study assessed the prevalence, predictors, and complications of EGV in aHCC patients treated with lenvatinib.
METHODS
In this multicenter international retrospective study, cirrhotic patients treated with lenvatinib for aHCC, were enrolled if upper-gastrointestinal endoscopy was available within 6 months before treatment. Primary endpoint was the incidence of EGV bleeding during lenvatinib therapy; secondary endpoints were predictors for EGV bleeding, prevalence, and risk factors for the presence of EGV and high-risk EGV at baseline, as well as impact of EGV bleeding on patients' survival.
RESULTS
535 patients were enrolled in the study (median age: 72 years, 78% male, 63% viral etiology, 89% Child-Pugh A, 16% neoplastic portal vein thrombosis [nPVT], 56% Barcelona Clinic Liver Cancer-C): 234 had EGV (44%), 70 (30%) were at high risk and 59 were on primary prophylaxis. During lenvatinib treatment, 17 patients bled from EGV (3 grade 5), the 12-month cumulative incidence being 3%. The only baseline independent predictor of EGV bleeding was the presence of baseline high-risk EGV (hazard ratio: 6.94, 95% confidence interval [CI]: 2.23-21.57, = 0.001). In these patients the 12-month risk was 17%. High-risk varices were independently associated with Child-Pugh B score (odds ratio [OR]: 2.12; 95% CI: 1.08-4.17, = 0.03), nPVT (OR: 2.54; 95% CI: 1.40-4.61, = 0.002), and platelets <150,000/μL (OR: 2.47; 95% CI: 1.35-4.50, = 0.003).
CONCLUSION
In hepatocellular carcinoma patients treated with lenvatinib, the risk of EGV bleeding was mostly low but significant only in patients with high-risk EGV at baseline.
PubMed: 38751557
DOI: 10.1159/000534127