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Purpose: Few studies have focused on the management of inoperable ampullary carcinoma (AC), and patients with jaundice suffer from biliary stents replacement frequently. Iodine-125 ( 125 I) brachytherapy has been used in the treatment of malignant tumors owing to its curative effect, minimal surgical trauma, and tolerable complications. The aim of the study was to investigate the role of 125 I seed implantation in patients with unresectable ampullary carcinoma after relief of obstructive jaundice., Material and Methods: A total of 44 patients with obstructive jaundice resulting from unresectable ampullary carcinoma from January 1, 2010 to October 31, 2020 were enrolled in the study. Eleven patients underwent implantation of 125 I seeds under endoscopic ultrasound (EUS) after receiving biliary stent placement via endoscopic retrograde cholangiopancreatography (ERCP) (treatment group), and 33 patients received a stent alone via ERCP (control group). Cox regression model was applied in this single-center retrospective comparison study., Results: The median maximum intervention interval for biliary obstruction was 381 days (interquartile range [IQR]: 204-419 days) in the treatment group and 175 days (IQR: 126-274 days) in the control group ( p < 0.05). Stent occlusion rates at 90 and 180 days in the control group were 12.9% and 51.6%, respectively. No stent occlusion occurred in the treatment group. Patients in the treatment group obtained longer survival time (median, 26 vs. 13 months; p < 0.01) and prolonged duodenal obstruction (median, 20.5 vs. 11 months; p < 0.05). No brachytherapy-related grade 3 or 4 adverse events were observed., Conclusions: Longer intervention interval for biliary obstruction and survival as well as better stent patency and prolonged time to duodenal obstruction could be achieved by implanting 125 I seeds combined with biliary stent in patients with unresectable ampullary cancer., Competing Interests: The study was reviewed and approved by the Ethics Committee of the PLA General Hospital (Approval No. S2021-309-03). The authors report no conflict of interest., (Copyright © 2024 Termedia.)

Purpose: The purpose of this study was to explore which therapeutic strategy is more beneficial for elderly esophageal cancer (EC) patients with distant metastasis, the treatment utilization status and the screening of factors related to prognosis, so as to better guide the treatment of these patients., Methods: Patients in the Surveillance Epidemiology and End Results (SEER) database were divided into chemoradiotherapy (Group A), chemotherapy (Group B), radiotherapy (Group C), and no treatment (Group D) according to different treatment methods. Propensity score matching (PSM) was performed to adjust for baseline differences between the two groups. Overall survival (OS) and esophageal cancer-specific survival (ECSS) was calculated using the Kaplan-Meier method and compared using the log-rank test., Results: A total of 7027 patients were included in this study, 5739 males (81.7%) and 1288 females (18.3%) with the median age was 70 (60-98). In the original cohort, the number of patients in the four groups was 2260 (Group A), 2087 (Group B), 945 (Group C) and 1735 (Group D), respectively. After PSM, there was no significant difference in mean OS (A vs B, 13.5 months VS 13.4 months, P = 0.511) and mean ECSS (A vs B, 15.6 vs 15.5 months, P = 0.374), while both OS (B vs C, 7 vs 3 months, P < 0.001) and ECSS (B vs C, 8 vs 3 months, P < 0.001) of chemotherapy alone were significantly better than those of radiotherapy alone. Subgroup analysis of patients older than 80 years showed that the median OS (A vs B, 7 vs 6 months) and median ECSS (A vs B, 8 vs 7 months) of Group A were significantly better than those of Group B (P < 0.05). In addition, all patients were randomly divided into a training set and a validation set with a ratio of 7:3. Based on the independent risk factors for OS, a nomogram model was constructed and validated., Conclusion: For elderly EC patients with distant metastasis, aggressive treatment was still necessary after a comprehensive assessment of the patient's physical condition, especially for patients over 80 years old, and chemoradiotherapy maybe still the first choice. In addition, a nomogram model was constructed to intuitively and accurately evaluate the prognosis of this population., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Biliary stents combined with percutaneous or endoscopic ultrasound-guided iodine-125 seed implantation into primary tumor have been confirmed to relieve malignant obstructive jaundice (MOJ), and prolong patient's stent patency. The aim of the study was to evaluate meaningful clinical application indications and better guide the application of this technology., Material and Methods: Patients with MOJ, who have received bile duct stenting combined with iodine-125 ( 125 I) seed implantation from October, 2010 to April, 2022, were retrospectively analyzed. Univariate and multivariate analyses were adopted to indicate factors of stent patency in MOJ and influencing factors of jaundice reduction at one week after surgery., Results: A total of 90 patients were enrolled into the study, including 52 males (57.8%) and 38 females (42.2%), with a mean age of 68.66 ±12.53 years. The median stent patency was 8 months. No serious adverse events occurred during follow-up. Multivariate analysis showed that Child-Pugh score (HR = 2.221, 95% CI: 1.081-4.562), biliary infection (HR = 1.901, 95% CI: 1.084-3.335), and pre-operative jaundice duration (HR = 1.977, 95% CI: 1.106-3.533) were the independent risk factors for stent patency. Child-Pugh B/C (OR = 4.647, 95% CI: 1.080-19.982) and bile duct infection (OR = 3.583, 95% CI: 1.095-11.725) were the independent risk factors for jaundice reduction at one week after surgery., Conclusions: MOJ patients treated with biliary stents combined with 125 I seed implantation, and patients with better pre-operative liver function and no biliary tract infection, present not only longer biliary stent patency, but also better early jaundice reduction., Competing Interests: The authors report no conflict of interest., (Copyright © 2022 Termedia.)

Background: Endoscopic papillectomy (EP) is an effective treatment for ampullary lesions but technically challenging because of anatomical specificities concerning the high rate of adverse events. Bleeding is one of the most feared complications and can be potentially life-threatening., Aim: To study the risk factors for bleeding after EP are presented with the goal of establishing preventive measures., Methods: A total of 173 consecutive patients with ampullary lesions undergone EP from January 2006 to October 2020 were enrolled in this study. They were divided into a bleeding group and a non-bleeding group depending on whether postoperative bleeding occurred. Related factors were analyzed by univariate and multivariate logistics regression., Results: Postoperative bleeding was experienced in 33 patients (19.07%). Multivariate analysis also identified intraoperative bleeding (OR: 4.38, 95% CI: 1.87-11.15, p =  .001) and endoscopic closure (OR: 0.25, 95% CI: 0.10-0.58, p =  .001) as independent factors significantly associated with bleeding after EP. Lesion size (≥3 cm) was shown as an independent factor significantly associated with intraoperative bleeding (OR: 4.25, 95% CI: 1.21-16.44, p =  .028)., Conclusions: This retrospective evaluation found that endoscopic closure was associated with reduced risk and intraoperative bleeding with increased risk of bleeding after EP. Lesion size may indirectly influence the risk of postoperative bleeding by increasing the risk of intraoperative bleeding.

With the advance of invasive interventions, the treatment model for infected necrotizing pancreatitis (INP) has shifted from open surgery to the step-up minimally invasive treatment. Late intervention, originating from the open surgery era, has been questioned in the minimally invasive period. With the emergence of new high-quality evidence about the timing for intervention, it seems to be increasingly apparent that, even in the age of minimal invasiveness, "late intervention" waiting for the necrotic collections to be encapsulated is still necessary. This opinion review mainly discusses the intervention timing for INP., Competing Interests: Conflict-of-interest statement: All authors report no relevant conflict of interest for this article., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Pancreatic and peripancreatic collections are the main local complications of acute pancreatitis with a high incidence. In the early phase, most acute pancreatic and peripancreatic collections can resolve spontaneously with supportive treatment. However, in some cases, they will develop into pancreatic pseudocyst (PPC) or walled-off necrosis (WON). When causing symptoms or coinfection, both PPC and WON may require invasive intervention. Compared to PPC, which can be effectively treated by endoscopic ultrasound-guided transmural drainage with plastic stents, the treatment of WON is more complicated and challenging, particularly in the presence of infected necrosis. In the past few decades, with the development of minimally invasive interventional technology especially the progression of endoscopic techniques, the standard treatments of those severe complications have undergone tremendous changes. Currently, based on the robust evidence from randomized controlled trials, the step-up minimally invasive approaches have become the standard treatments for WON. However, the pancreatic fistulae during the surgical step-up treatment and the stent-related complications during the endoscopic step-up treatment should not be neglected. In this review article, we will mainly discuss the indications of PPC and WON, the timing for intervention, and minimally invasive treatment, especially endoscopic treatment. We also introduced our preliminary experience in endoscopic gastric fenestration, which may be a promising innovative method for the treatment of WON., Competing Interests: Conflict-of-interest statement: There is no conflict of interest associated with any of the senior authors or other co-authors who contributed their efforts to this manuscript., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Health authorities require that suitable stability of the drug substance be shown in relevant materials of construction. ICH Q1A(R2) explicitly states that "stability studies should be conducted on drug substance packaged in a container closure system that is the same as or simulates the packaging proposed for storage and distribution". Stainless steel containers are commonly used for the long-term storage of frozen bulk drug substances (DSs). Hastelloy®-based metal containers are sometimes used due to their higher corrosion resistance and significantly lower iron content to mitigate the potential corrosion-related risks associated with high salt formulations. Despite their benefits, we have found that elevated temperature stability studies in small scale Hastelloy® containers can lead to degradation that is not representative of degradation under typical storage conditions relevant to the manufacturing process. We provide evidence for an oxidation-induced aggregation mechanism that is based on Fenton chemistry with peroxide being supplied by the autoxidation of polysorbate at stress temperatures. Further, variation in the rates of iron leaching between individual small scale containers is shown to be the cause of the variable rates of degradation through strong correlations between leached iron levels and the extents of oxidation and aggregation. The addition of a metal chelator or the removal of polysorbate from the formulation mitigates the oxidation and the non-representative behavior. Extended characterization by LC-MS and 18 O labeled peptide mapping shows that a significant portion of the aggregate formed under these conditions is covalently crosslinked and that the predominant covalent species is either a dityrosine or tyrosine-tryptophan crosslink between an Fc peptide and a Fab peptide. This report is the first time either of these two crosslinks have been reported for antibodies with detailed analytical characterization. Because the behavior observed in these studies is not representative of degradation under typical storage conditions relevant to the manufacturing process, this study demonstrates that small scale stress studies in metal containers should be performed with caution and that extended incubation times can lead to non-representative degradation mechanisms., (Copyright © 2020. Published by Elsevier Inc.)

Background: Hemolymphangiomas are rare malformations composed of both lymphatic and vascular vessels and are located in the pancreas, spleen, mediastinum, etc . Small intestinal hemolymphangioma is extremely rare and often presents as obscure gastrointestinal bleeding. It is rarely diagnosed correctly before the operation. Endoscopic injection sclerotherapy is usually used as a management of bleeding in esophageal varices and was occasionally reported as a treatment of vascular malformation. The treatment of small intestinal hemolymphangioma with enteroscopic injection sclerotherapy has not been reported., Case Summary: A 42-year-old male complained of recurrent episodes of melena and dizziness, fatigue and reduced exercise capacity for more than 2 mo. Gastroduodenoscopy and blood test revealed a gastric ulcer and anemia. Treatment with oral proton-pump inhibitors and iron did not improve symptoms. We then performed a capsule endoscopy and anterograde balloon-assisted enteroscopy and revealed a hemolymphangioma. Considering it is a benign tumor without malignant potential, we performed enteroscopic injection sclerotherapy. He was discharged 4 days later. At follow-up 3 mo later, the melena disappeared. Balloon-assisted enteroscopy revealed an atrophied tumor atrophied and no bleeding. Argon plasma coagulation was applied to the surface of the hemolymphangioma to accelerated healing. When he returned for follow-up 1 year later, anemia was resolved and the tumor had been cured., Conclusion: Balloon-assisted enteroscopy and capsule endoscopy are effective methods for diagnosis of hemolymphangioma. Enteroscopic injection sclerotherapy is an effective treatment., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) are a response to EGFR-tyrosine kinase inhibitor. However, a lack of sufficient tumor tissue has been a limitation for determining EGFR mutation status in clinical practice. The objective of this study was to predict EGFR mutation status in NSCLC patients based on a model including maximum standardized uptake value (SUVmax) and clinical features.We retrospectively reviewed NSCLC patients undergoing EGFR mutation testing and pretreatment positron emission tomography/computed tomography between March 2009 and December 2013. The relationships of EGFR mutations with both SUVmax and patient characteristics were evaluated, and a multivariate logistic regression analysis was performed. The model was assessed by area under the receiver-operating characteristic curve (AUC) and was prospectively validated during January to June 2014.Three hundred and sixteen patients meeting the criteria were enrolled for model construction. The SUVmax values were significantly lower for EGFR mutations (mean, 9.5 ± 5.74) than for EGFR wild-type (mean, 12.7 ± 6.43; P < 0.001). ROC curve analysis showed that the SUVmax cutoff point was 8.1, for which the AUC was 0.65 (95% confidence interval [CI], 0.60-0.72). In addition, multivariate analysis also showed that low SUVmax (≤8.1) was a predictor of EGFR mutations, for which the AUC was 0.77, combining nonsmoking history and primary tumor size (≤5 cm). Eighty-five patients were enrolled to validate the predictive model, and the overall accuracy, sensitivity, and specificity were 77.6%, 64.6% (95% CI 40.7-82.8), and 82.5% (95% CI 70.9-91.0), respectively.The specific FDG uptake value could be considered to effectively predict EGFR mutation status of NSCLC patients by considering smoking history and primary tumor size when genetic tests are not available., Competing Interests: The authors declare that they have no conflict of interest.

Leachables from single-use bioprocess containers (BPCs) are a source of process-related impurities that have the potential to alter product quality of biotherapeutics and affect patient health. Leachables often exist at very low concentrations, making it difficult to detect their presence and challenging to assess their impact on protein quality. A small-scale stress model based on assessing protein stability was developed to evaluate the potential risks associated with storing biotherapeutics in disposable bags caused by the presence of leachables. Small-scale BPCs were filled with protein solution at high surface area-to-volume ratios (≥3× the surface area-to-volume ratio of manufacturing-scale BPCs) and incubated at stress temperatures (e.g., 25 °C or 30 °C for up to 12 weeks) along with an appropriate storage vessel (e.g., glass vial or stainless steel) as a control for side-by-side comparison. Changes in protein size variants measured by size exclusion chromatography, capillary electrophoresis, and particle formation for two monoclonal antibodies using both the small-scale stress model and a control revealed a detrimental effect of gamma-irradiated BPCs on protein aggregation and significant BPC difference between earlier and later batches. It was found that preincubation of the empty BPCs prior to protein storage improved protein stability, suggesting the presence of volatile or heat-sensitive leachables (heat-labile or thermally degraded). In addition, increasing the polysorbate 20 concentration lowered, but did not completely mitigate, the leachable-protein interactions, indicating the presence of a hydrophobic leachable. Overall, this model can inform the risk of BPC leachables on biotherapeutics during routine manufacturing and assist in making decisions on the selection of a suitable BPC for the manufacturing process by assessing changes in product quality., Lay Abstract: Leachables from single-use systems often exist in small quantities and are difficult to detect with existing analytical methods. The presence of relevant detrimental leachables from single-use bioprocess containers (BPCs) can be indirectly detected by studying the stability of monoclonal antibodies via changes by size exclusion chromatography, capillary electrophoresis sodium dodecyl sulfate, and visible/sub-visible particles using a small-scale stress model containing high surface area-to-volume ratio at elevated temperature alongside with an appropriate control (e.g., glass vials or stainless steel containers). These changes in protein quality attributes allowed the evaluation of potential risks associated with adopting single-use bioprocess containers for storage as well as bag quality and bag differences between earlier and later batches. These leachables appear to be generated during the bag sterilization process by gamma irradiation. Improvements in protein stability after storage in "preheated" bags indicated that these leachables may be thermally unstable or volatile. The effect of surfactant levels, storage temperatures, surface area-to-volume ratios, filtration, and buffer exchange on leachables and protein stability were also assessed., (© PDA, Inc. 2016.)

Aim: To evaluate the outcomes of patients with end-stage biliary disease (ESBD) who underwent liver transplantation, to define the concept of ESBD, the criteria for patient selection and the optimal operation for decision-making., Methods: Between June 2002 and June 2014, 43 patients with ESBD from two Chinese organ transplantation centres were evaluated for liver transplantation. The causes of liver disease were primary biliary cirrhosis (n = 8), cholelithiasis (n = 8), congenital biliary atresia (n = 2), graft-related cholangiopathy (n = 18), Caroli's disease (n = 2), iatrogenic bile duct injury (n = 2), primary sclerosing cholangitis (n = 1), intrahepatic bile duct paucity (n = 1) and Alagille's syndrome (n = 1). The patients with ESBD were compared with an end-stage liver disease (ESLD) case control group during the same period, and the potential prognostic values of multiple demographic and clinical variables were assessed. The examined variables included recipient age, sex, pre-transplant clinical status, pre-transplant laboratory values, operation condition and postoperative complications, as well as patient and allograft survival rates. Survival analysis was performed using Kaplan-Meier curves, and the rates were compared using log-rank tests. All variables identified by univariate analysis with P values < 0.100 were subjected to multivariate analysis. A Cox proportional hazard regression model was used to determine the effect of the study variables on outcomes in the study group., Results: Patients in the ESBD group had lower model for end-stage liver disease (MELD)/paediatric end-stage liver disease (PELD) scores and a higher frequency of previous abdominal surgery compared to patients in the ESLD group (19.2 ± 6.6 vs 22.0 ± 6.5, P = 0.023 and 1.8 ± 1.3 vs 0.1 ± 0.2, P = 0.000). Moreover, the operation time and the time spent in intensive care were significantly higher in the ESBD group than in the ESLD group (527.4 ± 98.8 vs 443.0 ± 101.0, P = 0.000, and 12.74 ± 6.6 vs 10.0 ± 7.5, P = 0.000). The patient survival rate in the ESBD group was not significantly different from that of the ESBD group at 1, 3 and 5 years (ESBD: 90.7%, 88.4%, 79.4% vs ESLD: 84.9%, 80.92%, 79.0%, χ(2) = 0.194, P = 0.660). The graft-survival rates were also similar between the two groups at 1, 3 and 5 years (ESBD: 90.7%, 85.2%, 72.7% vs ESLD: 84.9%, 81.0%, 77.5%, χ(2) = 0.003, P = 0.958). Univariate analysis identified MELD/PELD score (HR = 1.213, 95%CI: 1.081-1.362, P = 0.001) and bleeding volume (HR = 0.103, 95%CI: 0.020-0.538, P = 0.007) as significant factors affecting the outcomes of patients in the ESBD group. However, multivariate analysis revealed that MELD/PELD score (HR = 1.132, 95%CI: 1.005-1.275, P = 0.041) was the only negative factor that was associated with short survival time., Conclusion: MELD/PELD criteria do not adequately measure the clinical characteristics and staging of ESBD. The allocation system based on MELD/PELD criteria should be re-evaluated for patients with ESBD.

Objective: Lung cancer is the leading cause of cancer-related death in the world, particularly in major cities in China. We aimed to determine the benefit of survival and toxicity of Conformal Radiotherapy (CRT) combined with erlotinib-based multimodality therapy in newly diagnosed metastatic non-small-cell lung cancer (NSCLC)., Patients and Methods: Newly diagnosed metastatic NSCLC patients were treated with CRT and erlotinib, with or without chemotherapy matched protocol. The patients received CRT with a dose of 30-66 Gy. Erlotinib was used at least one 28-day cycle. The primary end point was overall survival (OS)., Results: Thirty-two patients were analyzed. The median OS was 517 days. Patients with only one metastasis showed longer survival than patients with multi-metastases (986 vs. 380 days, n = 8 vs. 24, p = .009). Patients with multiple metastases in brain conferred worse survival for patients without and with sole brain metastasis (321 vs. 700 days, n=11 vs 21, p = .006). There was no significant difference in median survival whether erlotinib was used as a first-, second- or third-line therapy (380 vs. 700 vs. 310 days, n = 10 vs. 15 vs 7, respectively. p = .179). Patients with TTCRT > 90 days had longer OS than patients with TTCRT ≤ 90 days (749 vs. 322 days, n = 11 vs. 21, p = .012). Patients tolerated treatment with limited Grade 1/2 toxicity., Conclusions: In this study, patients with newly diagnosed metastatic NSCLC had survival benefits when erlotinib was used combined with CRT. Further prospective trials are needed to derive maximal benefit from the drug treatment.

Objective: To establish a stable and modified mouse model of brain death (BD) and to share our experiences in BD induction and maintenance., Methods: Totally 35 C57BL/6 male mice were randomized into BD group (n=25) or sham control group (n=10). BD was induced by inserting a 2F Fogarty catheter connected to a syringe pump after trepanation of the left frontoparietal area and injecting volume at the speed of 6 μl/min until spontaneous respiration ceased. BD was diagnosed by electroencephalogram, apnea testing,as well as testing of brain stem reflexes. Mechanical ventilation was performed by orotracheal intubation. Right carotid artery was intubated by a PE-10 cannula for the continuous monitoring of mean blood pressure (MAP) and heart rate (HR). The right external jugular vein was catheterized for volume resuscitation.The sham control group underwent the same procedure with catheter insertion but without balloon inflation.Livers were removed and fixed in paraffin to evaluate the histological alterations with the light microscopy., Results: Mouse models of BD were successfully established about 20 minutes after balloon inflation, and the mean balloon volume at the time of BD was (105.77 ± 21.57)μl. The MAP and HR rapidly increased on occurrence of BD and the peak value was (128.28 ± 17.16) mmHg and (434.16 ± 55.75) beat/min, respectively, which were significant higher than those in the sham control group at the same time point (P=0.000). During the 4-hour follow-up time, MAP and HR in 72% (18/25) of BD animals remained haemodynamically stable. No animal died due to anesthesia and surgical operation.Hepatic tissues in BD mice showed mild focal ischemic damages (cellular edema, congestion, and inflammatory infiltration), which were slighter and fewer in sham control group., Conclusion: The mouse model of BD was successfully established with lower surgical difficulty and can be performed in a standardized, reproducible and successful way.

Purpose: To investigate the cause of the observed instability of dulanermin in 100 ml polyolefin (PO) infusion bags containing saline., Methods: Diluted dulanermin in IV bags was collected and frozen prior to analysis by size exclusion chromatography. The UV absorption profiles of the IV bag solutions were characterized by using spectrophotometry. Inductively Coupled Plasma Mass Spectrometry (ICP-MS) measured the metal content. Leachables from IV bags were identified by LC-UV-high resolution MS/MS analysis., Results: An elevated loss of dulanermin monomers was observed only in 100 ml PO bags. These IV bag solutions have a compound that contains zinc and has absorbance at 320 nm. This compound was identified to be 2-Mercaptobenzothiazole, and its zinc salt and was found to come from the stopper used in the 100 ml PO bags. The manufacturer has subsequently corrected this problem by using non-latex components in the 100 ml PO IV bag., Conclusions: End-users need to be aware that IV bags made from a particular polymer by the same manufacturer may contain components or use a manufacturing process that results in a different product. Analysis of samples after freezing and thawing proved to be useful in identifying potential incompatibility of dulanermin in the IV bags.