Coil or Plug-Assisted Ethylene Vinyl Alcohol Copolymer (EVOH) Thoracic Duct Embolization in the Treatment of Postoperative Chylothorax.

Eleven patients (5 men, 6 women) with post-operative thoracic duct injuries and high output chylothorax were treated with thoracic duct embolization (TDE). Six patients underwent intraprocedural thoracic duct ligation at the time of original procedure. In all cases, the pleural fluid demonstrated high triglyceride levels (414 mg/dL; interquartile range [IQR], 345 mg/dL). Median daily (IQR) chest tube outputs before and after TDE were 900 mL (1,200 mL) and 325 mL (630 mL), respectively. Coil- or plug-assisted ethylene vinyl alcohol (EVOH) copolymer was used as embolic agent in all patients. Technical and clinical success rates were 100% and 82%, respectively. Nontarget venous embolization of EVOH copolymer was not identified on subsequent imaging.

Recurrence patterns after complex multimodality therapy and hepatic arterial infusion for colorectal liver metastases: A reflection of biology and technique.

BACKGROUND AND METHODS: We characterized colorectal liver metastasis recurrence and survival patterns after surgical resection and intraoperative ablation ± hepatic arterial infusion pump (HAIP) placement. We estimated patterns of recurrence and survival in patients undergoing contemporary multimodal treatments. Between 2017 and 2021, patient, tumor characteristics, and recurrence data were collected. Primary outcomes included recurrence patterns and survival data based on operative intervention. RESULTS: There were 184 patients who underwent hepatectomy and intraoperative ablation. Sixty patients (32.6%) underwent HAIP placement. A total of 513 metastases were ablated, median total of 2 ablations per patient. Median time to recurrence was 31 [22-40] months. Recurrence patterns included tumor at ablative margin on first scheduled postoperative imaging (8, 4.3%), local tumor recurrence at ablative site (69, 37.5%), and non-ablated liver tumor recurrence (38, 20.6%). In patients who underwent HAIP placement, the rate of liver recurrence was reduced (45% vs 70.9%, p = 0.0001). Median overall survival was 64 [41-58] months and prolonged survival was associated with HAIP treatment (85 [66-109] vs 60 [51-70] months. CONCLUSIONS AND DISCUSSION: Hepatic recurrence is common and combination of intraoperative ablation and HAIP treatments were associated with prolonged survival. These data may reflect patient selection however, future work will clarify preoperative tumor and patient characteristics that may better predict recurrence expectations.

Ablation Techniques in Cancer Pain.

Painful bone metastases are a frequently encountered problem in oncology practice. The skeletal system is the third most common site of metastatic disease and up to 85% of patients with breast, prostate, and lung cancer may develop bone metastases during the course of their disease.

A Comparison of Liver-Directed Therapy and Systemic Therapy for the Treatment of Liver Metastases in Patients with Gastrointestinal Neuroendocrine Tumors: Analysis of the California Cancer Registry.

PURPOSE: To compare the outcomes of patients with gastrointestinal neuroendocrine tumor liver metastases treated with liver-directed therapy (LDT) to those treated with systemic therapy (ST) in a statewide cancer database. MATERIALS AND METHODS: A retrospective study was performed of patients with metastatic gastrointestinal tract neuroendocrine tumors treated with either LDT or ST alone between the years 2000-2012 in the California Cancer Registry. Overall survival and disease-specific survival were assessed using multivariable Cox proportional hazards analysis and propensity score matching. RESULTS: A total of 154 patients (ST, n = 87 and LDT, n = 67) were studied. The median overall survival and disease-specific survival for patients that received ST was 29 and 35 months versus 51 and >60 months for patients that received LDT. On multivariate analysis, LDT and the resection of the primary tumor were associated with improved survival (hazard ratio [HR] 0.52, P = .002; HR 0.43, P = .001). Non-white race, Medicaid/uninsured status, and the presence of lung metastases were associated with poor survival (HR 1.76, P = .014; HR 2.29, P = .009; and HR 1.79, P = .031). Propensity score matching demonstrated an improvement in disease-specific survival for LDT compared to ST (HR 0.53, P = .036). The improvement in overall survival on propensity score matching did not achieve statistical significance (HR 0.70, P = .199). CONCLUSIONS: LDT is associated with improved overall and disease-specific survival as compared to ST in patients with gastrointestinal neuroendocrine tumor liver metastases. Further investigation is needed to determine whether combination or sequential treatment can improve outcomes in this population.

Management of early hepatocellular carcinoma: results of the Delphi consensus process of the Americas Hepato-Pancreato-Biliary Association.

BACKGROUND: There are many potential treatment options for patients with early stage hepatocellular carcinoma (HCC) and practice patterns vary widely. This project aimed to use a Delphi conference to generate consensus regarding the management of small resectable HCC. METHODS: A base case was established with review by members of AHPBA Research Committee. The Delphi panel of experts reviewed the literature and scored clinical case statements to identify areas of agreement and disagreement. Following initial scoring, discussion was undertaken, questions were amended, and scoring was repeated. This cycle was repeated until no further likelihood of reaching consensus existed. RESULTS: The panel achieved agreement or disagreement consensus regarding 27 statements. The overarching themes included that resection, ablation, transplantation, or any locoregional therapy as a bridge to transplant were all appropriate modalities for early or recurrent HCC. For larger lesions, consensus was reached that radiofrequency ablation and microwave ablation were not appropriate treatments. CONCLUSION: Using a validated system for identifying consensus, an expert panel agreed that multiple treatment modalities are appropriate for early stage HCC. These consensus guidelines are intended to help guide physicians through treatment modalities for early HCC; however, clinical decisions should continue to be made on a patient-specific basis.

Lymphovascular Invasion Predicts Lymph Node Involvement in Small Pancreatic Neuroendocrine Tumors.

INTRODUCTION: Pancreatic neuroendocrine tumors (p-NETS) are increasing in incidence, and prognostic factors continue to evolve. The benefit of lymphadenectomy for p-NETS ≤2 cm remains unclear. We sought to determine the significance of lymphovascular invasion (LVI) for small p-NETS. METHODS: The National Cancer Database was queried for patients with p-NETS ≤2 cm and with ≥1 evaluated lymph node (LN), years 2004-2015. Demographic, clinical, and treatment characteristics were analyzed. Multivariate logistic regression was performed to identify predictors of LN positivity. RESULTS: Among 2,499 patients identified, tumor location was delineated as the head (26%), body (18%), tail (38%), or unspecified (18%); 74% were well-differentiated versus 10% moderate, 2% poor, and 14% unknown. LVI occurred in 11%. A median of 9 LNs were evaluated; overall positivity was 18%. Mean survival was significantly longer in node-negative patients (115 vs. 95 months, log-rank p < 0.0001). LVI was the strongest predictor of node involvement (OR 10.4, p < 0.0001) when controlling for tumor size, grade, and location. Subset analysis of patients with known LVI status, grade, location, and mitoses found that LVI was more likely in the setting of moderate-to-high tumor grade, 1-2 cm size, pancreatic head location, and high mitotic rate. Among patients with ≥2 of these 4 factors, 25% were node-positive. CONCLUSIONS: Presence of LVI was the strongest predictor of node positivity. LVI on endoscopic biopsy should prompt resection and regional LN dissection to fully stage patients with small p-NETS. Patients with other high-risk factors should also be considered for resection and regional lymphadenectomy.

A NIMA-Related Kinase Suppresses the Flagellar Instability Associated with the Loss of Multiple Axonemal Structures.

CCDC39 and CCDC40 were first identified as causative mutations in primary ciliary dyskinesia patients; cilia from patients show disorganized microtubules, and they are missing both N-DRC and inner dynein arms proteins. In Chlamydomonas, we used immunoblots and microtubule sliding assays to show that mutants in CCDC40 (PF7) and CCDC39 (PF8) fail to assemble N-DRC, several inner dynein arms, tektin, and CCDC39. Enrichment screens for suppression of pf7; pf8 cells led to the isolation of five independent extragenic suppressors defined by four different mutations in a NIMA-related kinase, CNK11. These alleles partially rescue the flagellar length defect, but not the motility defect. The suppressor does not restore the missing N-DRC and inner dynein arm proteins. In addition, the cnk11 mutations partially suppress the short flagella phenotype of N-DRC and axonemal dynein mutants, but do not suppress the motility defects. The tpg1 mutation in TTLL9, a tubulin polyglutamylase, partially suppresses the length phenotype in the same axonemal dynein mutants. In contrast to cnk11, tpg1 does not suppress the short flagella phenotype of pf7. The polyglutamylated tubulin in the proximal region that remains in the tpg1 mutant is reduced further in the pf7; tpg1 double mutant by immunofluorescence. CCDC40, which is needed for docking multiple other axonemal complexes, is needed for tubulin polyglutamylation in the proximal end of the flagella. The CCDC39 and CCDC40 proteins are likely to be involved in recruiting another tubulin glutamylase(s) to the flagella. Another difference between cnk11-1 and tpg1 mutants is that cnk11-1 cells show a faster turnover rate of tubulin at the flagellar tip than in wild-type flagella and tpg1 flagella show a slower rate. The double mutant shows a turnover rate similar to tpg1, which suggests the faster turnover rate in cnk11-1 flagella requires polyglutamylation. Thus, we hypothesize that many short flagella mutants in Chlamydomonas have increased instability of axonemal microtubules. Both CNK11 and tubulin polyglutamylation play roles in regulating the stability of axonemal microtubules.

Outcomes of Salvage Percutaneous Biliary Drainage after Occlusion of Endoscopic Stents.

PURPOSE: To describe outcomes of patients with malignant biliary obstruction who undergo salvage percutaneous biliary drainage after occlusion of endoscopic biliary stents. MATERIALS AND METHODS: A single-center retrospective review was performed of 47 patients (25 men, 22 women) who underwent percutaneous biliary drainage for recurrent obstruction after endoscopic stent placement between 2005 and 2015. Primary malignancies were bile duct (n = 13), colorectal (n = 11), gallbladder (n = 7), pancreas (n = 5), hepatocellular (n = 4), and other (n = 7). Indication for salvage drain placement was infection (n = 19) and jaundice or need to decrease bilirubin (n = 28). Kaplan-Meier and Cox regression methods were used for survival analysis. Logistic and multivariate regressions were employed to identify factors associated with survival. RESULTS: Median survival after salvage biliary drain placement was 1.8 months (95% confidence interval [CI], 1.3-2.7). Elevated international normalized ratio (INR) ≥ 1.5 before drainage was associated with poorer survival after drainage (median survival 0.7 months vs 2.4 months, P < .01). Median survival was shorter in 28 patients (64%) with bilirubin ≤ 2 mg/dL (34.2 µmol/L) after drainage (1.2 months vs 5.4 months, P < .001). Left-sided drain placement, elevated bilirubin, and elevated INR correlated with decreased likelihood of achieving bilirubin ≤ 2 mg/dL (34.2 µmol/L) (odds ratio [OR] 0.13, 95% CI, 0.02-0.71, P = .02; OR 0.18, 95% CI, 0.05-0.69, P = .01; OR 0.10, 95% CI, 0.01-0.90, P = .04). CONCLUSIONS: Survival is limited for most patients who undergo salvage percutaneous biliary drainage. Elevated bilirubin and INR before drainage portend a poor prognosis.

Radioembolization following Liver Resection: Safety and Dosing Considerations.

PURPOSE: To evaluate the impact of previous liver resection on the safety of resin microsphere radioembolization (RE). MATERIALS AND METHODS: A single-center retrospective review was performed of 22 patients who underwent resin microsphere RE after liver resection during the period 2009-2014. Prescribed patient dose using the body surface area (BSA) model and a theoretical dose calculated from the actual liver volume on imaging were recorded. Patient and treatment characteristics were analyzed for factors that contributed to toxicity. RESULTS: In 13 patients, 20 grade 1-3 toxicities were identified. No differences in toxicity were seen based on extent of prior hepatic resection or whether whole-liver treatments were performed (P = .2). The measured liver volume based on cross-sectional imaging correlated poorly with the expected liver volume based on BSA (r = 0.43). After adjusting for the patients' measured liver volume on cross-sectional imaging, five patients were determined to be relatively overdosed and seven patients were determined to be relatively underdosed by the BSA method. Despite these differences, no association was found with patient toxicities and either an overestimation or an underestimation of liver volume (P = .4). CONCLUSION: Previous hepatic resection does not adversely alter the safety profile of yttrium-90 RE. BSA poorly predicts expected liver volume in this population. However, standard BSA-based dosing and whole-liver remnant treatments do not increase hepatotoxicity.

Colorectal liver metastases: making the unresectable resectable using irreversible electroporation for microscopic positive margins - a case report.

BACKGROUND: Irreversible electroporation (IRE) is a non-thermal injury tissue ablation technique that uses electrical pulses to cause cell death. IRE damages the endothelial cells of blood vessels; however these cells re-grow, and thus IRE does not result in permanent damage to blood vessels. We report the novel use of IRE for ablation of microscopically positive margins after resection of colorectal liver metastases (CRLM) impinging on hepatic veins. CASE PRESENTATION: A 68-year-old female was found to have colon cancer and synchronous bilateral unresectable liver metastases. Chemotherapy with FOLFOX and cetuximab was initiated, with subsequent conversion to resectability of the CRLM. The patient underwent colectomy followed by right liver posterior sectionectomy with wedge resection of segment 5. Resection of tumor impinging on the left and middle hepatic veins would have required left hepatectomy, with insufficient remnant liver volume. The CRLM were meticulously dissected off the hepatic veins leaving a microscopically positive margin, and IRE was then used for margin ablation, leaving intact hepatic veins and venous blood flow. The patient is alive and without recurrent disease now 30 months after resection. Herein we review the IRE technology and its use in ablation of liver metastases. CONCLUSIONS: Use of IRE margin ablation for microscopically-positive CRLM resection may lead to long-term patient survival; further prospective randomized trials are needed to confirm this finding.

Large hepatic biloma after bland hepatic arterial embolization using antireflux catheter.

To our knowledge, there have been no previous reports of biliary injury or bilomas due to microvalve infusion catheters (Trinav Infusion System; Westminster, CO). Here, we describe an interesting case of large hepatic biloma following bland hepatic arterial embolization with an antireflux catheter.

Computed Tomography Angiography and Conventional Angiography for the Diagnosis and Treatment of Non-variceal Gastrointestinal Bleeding at a Tertiary Cancer Center.

INTRODUCTION: To evaluate the diagnostic value of computed tomography angiography (CTA) and conventional angiography (CA) and the therapeutic value of transarterial embolization for acute gastrointestinal bleeding in patients with malignancy. METHODS: A retrospective review of 100 patients who underwent CTA and/or CA for gastrointestinal bleeding at a comprehensive cancer center between the years 2011-2021 was performed. Clinical and patient outcome data were collected and analyzed using Kruskal-Wallis tests for continuous variables and chi-square tests or Fisher's exact tests (whichever is appropriate) for categorical variables in univariate analysis. All tests were two-sided at a significance level of 0.05. Analyses were performed using SAS version 9.4 (SAS Institute, Cary, NC). RESULTS: Fifty-two percent of our patients underwent CTA alone, 29% underwent CA alone, and 19% underwent both procedures. Overall, CTA was positive in 11.3% (8/71) of patients and CA was positive in 22.9% (11/38) of patients. Of patients who underwent both studies, 52.6% (10/19) were positive for both. ICU admission was associated with CTA and/or CA positivity (p=0.015). Of 48 patients with data for embolization, 50% of patients underwent transarterial embolization for bleeding, 11 patients had identifiable bleeding on CA, and 13 patients underwent prophylactic embolization at the site of suspected bleeding. Rebleeding following embolization was found in 33.3% (8/24) of patients, including six patients who underwent prophylactic embolization and two patients who were treated for visualized bleeding. CONCLUSION: CTA and CA are two critical studies for patients with GI bleeding and a history of malignancy. Neither alone can effectively exclude an identifiable source of bleeding. In patients with a history of malignancy, transarterial embolization may be an effective treatment of both angiographically visible and occult sources of GI bleeding.

CF33-hNIS-anti-PD-L1 oncolytic virus followed by trastuzumab-deruxtecan in a patient with metastatic triple negative breast cancer: a case study.

Prognosis of metastatic triple negative breast cancer (mTNBC) remains poor despite recent advances in therapeutic options. Trastuzumab deruxtecan (T-DXd) has shown promising efficacy in patients with human epidermal growth factor receptor 2 (HER2)-low breast cancer, which is defined by immunohistochemistry (IHC) 1+ or 2+ and lack of HER2 amplification by fluorescence in situ hybridization (FISH) testing. The purpose of the study is to evaluate the safety and initial evidence of efficacy of intratumoral administration of CF33-hNIS-anti-PD-L1 (CHECKvacc) against mTNBC. Oncolytic virus CHECKvacc intratumoral injection is currently undergoing investigation in patients with mTNBC as a single agent (NCT05081492). The patient was enrolled on the clinical trial CHECKvacc for the Treatment of Metastatic Triple Negative Breast Cancer, received a single dose of CHECKvacc, and discontinued the study due to lack of immediate response. We report a case of a patient with mTNBC who was heavily pretreated and presented with extensive dermal metastasis. Two dermal metastasis biopsies in 2021 showed HER2 0 by IHC. The patient received a single dose of CHECKvacc and discontinued the study due to lack of immediate response. Twenty-five days later, the patient received treatment with T-DXd, and her tumor regressed significantly. The patient's disease-free survival was 10 months (December 2021-October 2022). The sequential treatment with intratumoral injection of CHECKvacc followed by T-DXd may have significant clinical activity in select patients with heavily pretreated mTNBC. ClinicalTrials.gov NCT05081492.

Single-image diffusion coefficient measurements of proteins in free solution.

Diffusion coefficient measurements are important for many biological and material investigations, such as studies of particle dynamics and kinetics, and size determinations. Among current measurement methods, single particle tracking (SPT) offers the unique ability to simultaneously obtain location and diffusion information about a molecule while using only femtomoles of sample. However, the temporal resolution of SPT is limited to seconds for single-color-labeled samples. By directly imaging three-dimensional diffusing fluorescent proteins and studying the widths of their intensity profiles, we were able to determine the proteins' diffusion coefficients using single protein images of submillisecond exposure times. This simple method improves the temporal resolution of diffusion coefficient measurements to submilliseconds, and can be readily applied to a range of particle sizes in SPT investigations and applications in which diffusion coefficient measurements are needed, such as reaction kinetics and particle size determinations.

Gastrostomy tubes: Fundamentals, periprocedural considerations, and best practices.

Gastrostomy tube placement is a procedure that achieves enteral access for nutrition, decompression, and medication administration. Preprocedural evaluation and selection of patients is necessary to provide optimal benefit and reduce the risk of adverse events (AEs). Appropriate indications, contraindications, ethical considerations, and comorbidities of patients referred for gastrostomy placement should be weighed and balanced. Additionally, endoscopist should consider either a transoral or transabdominal approach is appropriate, and radiologic or surgical gastrostomy tube placement is needed. However, medical history, physical examination, and imaging prior to the procedure should be considered to tailor the appropriate approach and reduce the risk of AEs.

Presentation and survival of gastro-entero-pancreatic neuroendocrine tumors in young adults versus older patients.

BACKGROUND: A minority of patients with gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs) is diagnosed at younger age. This population-based study explores the broad clinical and pathologic features of the youngest 5% of adult patients with GEP-NETs. METHODS: A retrospective study of the National Cancer Database (NCDB) of patients with a primary GEP-NET was performed. Patients were stratified by age. Kaplan-Meier and multivariate Cox proportional hazards analyses were performed. RESULTS: We identified 31,983 patients with a diagnosis of a GEP-NET and only 5% of patients were under the age of 35. Young patients were found to have greater proportions of localized, well differentiated disease. On multivariate analysis, young age, well differentiated histology, early stage, and surgical intervention were associated with lower risk of mortality. CONCLUSIONS: Young patients with GEP-NETs tend to have earlier stage of presentation and well differentiated tumors, which may be most amenable to surgical intervention.

Combination of yttrium-90 radioembolization with stereotactic body radiation therapy in the treatment of portal vein tumor thrombosis.

PURPOSE: Portal vein tumor thrombosis (PVTT) from cancer involving the liver carries a dismal prognosis, with median overall survival (OS) ranging from 2 to 5 months. While treatment with yttrium-90 (90Y) radioembolization alone may improve outcomes, overall prognosis remains poor. We hypothesize that the combination of 90Y radioembolization to the parenchymal component of the tumor and stereotactic body radiation therapy (SBRT) to the vascular component is a safe and effective means of improving outcomes. MATERIALS AND METHODS: A single center retrospective review identified 12 patients with cancers involving the liver who received both 90Y radioembolization and SBRT to the PVTT between May 2015 to August 2020. Primary endpoint was the 90-day toxicity rate by the Common Terminology Criteria for Adverse Events version 5.0. Secondary endpoints were the best response rate based on the Response Evaluation Criteria in Solid Tumors v1.1, local control rate, portal vein (PV) patency rate, and median OS. RESULTS: Patients received a median 90Y dose of 104.3 Gy (range, 83.3 to 131.7 Gy) and a median 5-fraction SBRT dose of 32.5 Gy (range, 27.5 to 50 Gy). There were no late toxicities reported, and only 7 acute grade 1 toxicities reported: elevation of liver function tests (17%), nausea (17%), fatigue (17%), and esophagitis (8%). Local control was 83%. 58% of patients had a patent PV after treatment. With a median follow-up time of 28 months, 1-year OS was 55% with a median OS of 14 months. CONCLUSION: Combination 90Y radioembolization and SBRT appears to be safe and effective in the treatment of PVTT. Larger prospective studies are warranted to better evaluate this combination treatment approach.

Patterns of Whole Exome Sequencing in Resected Cholangiocarcinoma.

BACKGROUND: With minimally effective chemotherapy options, cholangiocarcinoma patients have 5 year survival rate of 10%. Tumor genetic profiling (TGP) can identify mutations susceptible to targeted therapies. We sought to describe the use of TGP and frequency of actionable results in resected cholangiocarcinoma. METHODS: A retrospective review of patients undergoing curative intent resection at a comprehensive cancer center (2010-2020). Clinicopathologic and partial or whole exome sequencing data were reviewed. RESULTS: 114 patients (mean age 65 ± 11 years, 45% female) underwent resection of cholangiocarcinoma (46% poorly differentiated, 54% intrahepatic, 36% node positive, 75% margin negative). Additionally, 32% of patients underwent TGP, yielding a mean of 3.1 actionable mutations per patient (range 0-14). Mutations aligned with a median of one drug per patient (range 0-11). Common mutations included TP53 (33%), KRAS (31%), IDH1/2 (14%), FGFR (14%), and BRAF (8%). Targeted therapies were administered in only 4% of patients (23% of eligible sequenced patients). After a median 22 months, 23% had recurrence and 29% were deceased. DISCUSSION: TGP for cholangiocarcinoma has increased over the last decade with targeted therapies identified in most sequenced tumors, impacting treatment in a quarter of eligible patients. Precision medicine will play a central role in the future care of cholangiocarcinoma.