Outcomes of Yttrium-90 Radioembolization for Unresectable Combined Biphenotypic Hepatocellular-Cholangiocarcinoma

Clinical question
What is the hepatic response and overall survival following Y-90 radioembolizations in patients with hepatocellular-cholangiocarcinoma (cHCC-CC)?

Take-away point
Y90 radioembolization is a potential treatment option for cHCC-CC as a well tolerated procedure and reasonable response rates.

Reference
Christopher D. Malone et al. Outcomes of Yttrium-90 Radioembolization for Unresectable Combined Biphenotypic Hepatocellular-Cholangiocarcinoma. Journal of Vascular and Interventional Radiology. May, 2020: 31; 5.

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Study design 

Retrospective Review

Funding source

Self-funded or unfunded

Setting

Single-Center

Figure 2. Kaplan-Meier survival curves and univariate Cox proportional hazard models of factors predicting survival after radioembolization. (a, b) Having > 1 tumor (a) and bilobar disease (b) both protended a >3 times increase in hazard of survival after radioembolization. (c) Although not statistically significant, there was a strong trend toward increased hazard of survival in nonresponders to radioembolization after treatment. (d) CA 19-9 level > 101.3 before treatment, which was derived from Youden statistic, portended a > 4 times increased hazard of survival after radioembolzation.

Summary

To date, there is little research concerning liver-directed therapy for combined biphenotypic hepatocellular-cholangiocarcinoma (cHCC-CC), with most being small series involving TACE. This is a rare primary malignancy with prognosis similar to cholangiocarcinoma. There are no consensus treatment guidelines to date.

This study evaluated 22 patients with biopsy confirmed cHCC-CC who underwent a total of 29 Y90 treatments utilizing resin microspheres. Overall survival and tumor response was analyzed. Median overall survival was 9.3 months following radioembolization. Complete response was seen in 15% with partial response in 40% of patients. The procedure was well tolerated with the majority of toxicities categorized as Grade 1 or 2. Poor prognostic indicators included bilobar disease, greater than one tumor, and elevated CA 19-9 levels.

Commentary

With surgical resection and transplantation often not an option for patients with cHCC-CC, liver directed therapies are likely to be a major treatment option for palliation. Interestingly, the overall survival rates reported in this study were significantly shorter than studies utilizing chemoembolization in Asia. However, given the incredible variability in tumor biology involving cHCC-CC, this could be explained by a population more resembling cholangiocarcinoma than hepatocellular carcinoma. However, the role of Y90 in treatment cHCC-CC remains unclear, especially as it should be positioned against TACE.

This study is limited by factors that limit many Y90 trials including small patient size and variable previous and future treatment regimens. Future studies are needed to compare Y90 to TACE in this population to help guide treatment guidelines.


Post Author:
David M Mauro, MD
Assistant Professor
Department of Radiology, Vascular and Interventional Radiology
University of North Carolina

@DavidMauroMD

Gallbladder Cryoablation for Chronic Cholecystitis in High-Risk Surgical Patients: 1-Year Clinical Experience with Imaging Follow-up

Clinical question
Does gallbladder cryoablation produce safe and efficacious results in non surgical candidates?

Take away point
Cryoablation was technically successful in 6 of 7 patients, with resolution of abdominal symptoms in all 6 patients post-ablation without recurrence over the follow-up period, and 2 adverse events.

Reference
Gallbladder Cryoablation for Chronic Cholecystitis in High-Risk Surgical Patients: 1-Year Clinical Experience with Imaging Follow-up. McGregor, Hugh et al. Journal of Vascular and Interventional Radiology, Volume 31, Issue 5, 801 - 807

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Study design
Single arm, single institution, retrospective, cohort study

Funding source
No reported funding

Setting
Academic hospital, University of Arizona, USA





Figure 6
Axial T2-weighted (a) and contrast-enhanced T1-weighted (b) MR images obtained 12 months post gallbladder cryoablation demonstrating complete involution of the gallbladder (white arrow). Note the tortuous cystic duct (black arrow).

Summary

Cholecystectomy tubes are the current primary option to treat non-surgical candidates with cholecystitis, however can impact quality of life and often result in recurrence after removal. Gallbladder cyroablation is a potential alternative minimally invasive definite treatment. Recently the first human gallbladder cyroablation was reported with clinical and imaging success at 3 months. The authors currently further investigate the viability of gallbladder cryoablation and retrospectively studied 7 consecutive patients who underwent the procedure from August 2018 to July 2019 and evaluated symptoms, adverse events and imaging over the available follow up period (mean =278 days).

The patients studied were adults with cholecystitis or intractable biliary cholic deemed non-surgical candidates by their respective attending surgeons, with a variety of comorbidities, and a mean American Society of Anesthesiologists score of 3.7. At time of ablation, all patients were afebrile and without leukocytosis, 5 were with indwelling cholecystectomy tube, and 1 had ongoing intermittent abdominal pain.

Prior to procedure, intravenous antibiotics was administered and aspiration of present gallbladder contents using existing or new catheter was performed. Initially contrast dissection was performed through percutaneous Yueh catheters to create at least 1 cm separation of gallbladder from colon and/or duodenum. Cyroablation was performed with placement of cyroprobes to achieve iceball coverage of at least 5 mm beyond gallbladder wall and of the cystic duct. Cholecystectomy catheters were removed immediately post procedure in 5 patients, and at post-procedure day 11 in 1 patient due to persistent pain.

Patients were followed up with common labs up to 6 months, and CT/MR up to 12 months where possible. One of 7 procedures was not successful due to adhesions preventing safe dissection of gallbladder from colon, and was excluded from follow up analysis. All 6 were free of abdominal pain at 14 days post ablation. Follow-up labs out to 3 months were mostly unchanged compared to pre-procedure; two patients had mild leukocytosis, 3 had elevated transaminases at day 1, and 1 patient with renal failure had elevated creatine at 1 month. There were two adverse events; one patient with severe cirrhosis on day 3 developed intra abdominal hemorrhage without a source and stabilized with correction of coagulopathy. A second patient on day 5 developed abdominal pain and was found to have fluid filled gallbladder with inflammatory changes which required temporary drain. Two patients died over the follow up period of unrelated causes. Some degree of gallbladder involution was demonstrated in 5 patients over the 12 month follow-up period, with eventual complete gallbladder involution demonstrated in all 4 alive patients. All 5 patients who underwent 1 month HIDA scan demonstrated occlusion of the cystic duct.

The 46 % rate of recurrent calculous cholecystitis in general patients after cholecystectomy tube removal introduces the possibility that the study patients may have become symptom free after their tube removal regardless of ablation. However imaging evidence of gallbladder devitalization occurred in 5 of 6 patients, although the excluded patient only had one 3 month CT scan before death. The authors suggest that large gallstones may have prevented gallbladder wall apposition in the last patient, thus removing gallstones prior to cyroablation should be considered in the future. Additionally both adverse events occurred in patients with large gallstones; it is possible that gallstone bacteria incited hepatic decompensation in the cirrhotic patient and resulted in post procedural infection in the second patient who required temporary drain. Gallbladder cyroablation is anatomically feasible and demonstrated good technical success without non target ablation. Additionally, the positive study results indicate cryoablation is a viable option in the selected patient population.

Commentary

The authors in the study compounded their investigation into gallbladder cryoablation by assessing 7 consecutive ablation patients, including the previously reported first human case, over an increased follow up period of 12 months. Cholecystectomy tubes for non-surgical candidates with cholecystitis have limitations and thus the study serves an important role, to evaluate cryoablation as an alternative definite management option. The results are encouraging with high degrees of technical success, symptom resolution, imaging evidence of gallbladder devitalization, and relatively low clinical harm over the follow up period. The authors acknowledge the limitations of a small and heterogenous sample population as well as the lack of histologic confirmation of gallbladder devitalization. Thus, in addition to larger power studies, future reports with an even longer follow up period to confirm stability of gallbladder involution appearance on imaging as well as lack of recurrence of symptoms may add value. Additionally the authors suggest that the presence of large gallstones may have contributed to the adverse events as well as interfered with tracking gallbladder involution on imaging. Future studies with pre-procedural optimization to reduce gallstones would be of interest.

Post author

Ranjan Ragulojan, MD
DR resident R-1
University of Minnesota
@Ragulojan

Hemodialysis Catheters in Infants: A Retrospective Single-Center Cohort Study

Clinical questionWhat are technical aspects and outcomes of insertion/maintenance of hemodialysis central venous catheters (HD-CVCs) in infants?

Take away pointIn infants, HD-CVCs require technical modifications and multiple maintenance procedures. Occlusive thromboses are frequent. Non-tunneled HD-CVCs are associated with higher catheter-related infection and may have higher thrombosis rates compare to tunneled HD-CVCs.

Reference
Ma GMY, Ventura LM, Amiribadi A, et al. Hemodialysis Catheters in Infants: A Retrospective Single-Center Cohort Study. J Vasc Interv Radiol. 2020;31(5):778-786.

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Study design
Single-center, retrospective cohort study

Funding source
No reported funding

Setting
The Hospital for Sick Children, University of Toronto, Toronto, ON

Figure A 22-day-old male, 3.1 kg, with nephrotic syndrome and ESRD requiring hemodialysis. An 8 F, 15-cm cuff-to-tip, Medcomp HD-CVC was inserted after trimming the catheter’s proximal lumen (venous return). (a) Note the location of the catheter hub (*) and overall line length with respect to the patient’s chest size. (b) Note the distance between both lumens ([) and its position in the right atrium despite trimming the catheter. The atriocaval junction (arrow) is estimated at 2 vertebrae below the carina, around T6.

Summary

Children suffering from end-stage renal disease (ESRD) require renal replacement therapy (RRT) or transplantation to survive. While renal transplantation offers the best prognosis, it is not offered to children under the age of 24 months or weight of 10 kg. Children under the age of 2 years can receive RRT via peritoneal dialysis (PD) or hemodialysis (HD), with PD being the most commonly used due to several known benefits over HD. HD must be resorted to, however, when PD fails or is contraindicated. This must be done with central venous catheters (CVCs) in this population due to problematic nature of arteriovenous fistulas in children under 10 kg. The placement and maintenance of CVCs for HD in infants has not been well-studied. This study aimed to evaluate outcomes and challenges in CVC insertion and maintenance in these patients.

In this retrospective cohort study, 29 patients who had undergone initial CVC placement for HD before the age of 1 year were identified over a 14-year period (2002-2016). Both tunneled and non-tunneled CVCs, as well as both upper and lower CVCs were included. Non-IR-placed CVCs as well as CVCs placed for indications other than HD were excluded. CVC-related adverse events and dialysis sessions were assessed through 1 year of life and overall outcomes were assessed until December 2017 or death. Measured procedural details included procedure outcome, modifications, and complications. Postprocedural details included number of dialysis cycles, HD sessions, device service intervals, total access site service interval, CVC maintenance procedures, adverse events, and status at final review.

Out of the 29 patients analyzed, 13 (45%) were neonates when RRT was initiated. 10 patients received initial RRT via PD before switching to HD while 19 started with HD. 49 CVCs were placed in these patients (15 non-tunneled and 34 tunneled). Modifications were used in 51% of all catheter placements (33% of non-tunneled and 59% of tunneled CVCs) to allow for proper tip placement. For upper venous system CVCs, these modifications included suturing the catheter to the patient’s scalp behind the ipsilateral ear (n=4) and suturing to the scalp with placement of CVC tip in the IVC (n=1), trimming the tip to reduce distance between staggered ends (n=17), and tip trimming with catheter pullback and burying the cuff in a caudal extension of the tunnel (AKA “T-incision,” n=3). Technical success of modifications was 94% with no statistical difference between catheter types.

Mean number of dialysis cycles was 2.3 (range 1-6), with means of 4.1 sessions/catheter for non-tunneled CVCs and 49 sessions/catheter for tunneled CVCs. 26 (53%) CVCs required IR maintenance procedures, including 1 non-tunneled and 25 tunneled CVCs in 13 patients. Procedures included 25 contrast evaluations, 6 re-suturings, 1 repositioning of a non-tunneled CVC, and 13 catheter exchanges. Exchanges were done due to fibrin sheath formation (n=3), CVC fracture (n=2), malposition/dislodgement (n=7), or CVC disfunction (n=2). Difference in IR maintenance rates/1000 catheter-days was not significant between catheter types (p=0.454). Non-tunneled catheters had significantly decreased mean number of sessions/catheter (p < 0.002), dwell time (p < 0.004), primary device service interval (p < 0.002), and total access site interval (p < 0.001).

A total of 6 intraprocedural adverse events occurred, including 3 episodes of prolonged bleeding, 2 patients requiring second puncture, and 1 episode of profound hypotension of uncertain etiology after CVC insertion. 5 catheter-related bloodstream infections (CRBSIs) occurred in 4 patients, including 4 tunneled and 1 non-tunneled CVC. Infection rate was 1.03 infections/1000 catheter-days, with non-tunneled CVCs having a rate of 9.25 infections/1000 catheter-days and tunneled catheters having a rate of 0.83/1000 catheter-days (p < 0.02). Symptomatic thrombosis was identified in 10/29 patients (34%) and 12/49 catheters (24%), with 8 jugular venous thromboses and 4 femoro-iliac venous thromboses. 8 were occlusive and 4 were non-occlusive. An additional 4 patients experienced 4 asymptomatic occlusions discovered incidentally during CVC placement. 2 patients with upper venous system thrombosis developed chylothorax after CVC placement, associated with 1 death at 2 years of age. There was no difference in fibrin sheath or thrombosis incidence between trimmed and non-trimmed catheters (p=0.422). Patients with tunnel extensions were associated with an increase in cuff exposures compared to non-extended tunnels (p = 0.011).

10 patient deaths occurred during infancy, of which none were due to catheter-related complications. 3 deaths were defined as late deaths, occurring at 16 months (renal failure), 2 years (chylothorax/plastic bronchitis/vascular stenting), and 10 years (transplant complications) of patient age. The chylothorax-related death was attributed to a delayed complication of catheter placement. 19 patients survived past infancy, with 8 surviving past organ transplant (53%), 2 remaining on HD, 3 receiving RRT via PD, and 1 fully recovering renal function. 2 patients were lost to follow-up.

Commentary

This investigation sought to identify procedural particularities and catheter-related outcomes in patients undergoing CVC placement for HD prior to 1 year of age. The mortality, rate of renal transplantation, vascular occlusion rate, and CRBSI rates were all within expected ranges. Technical success in cases requiring modification was high and did not differ with catheter type. Interestingly, the practice of trimming the tip of the catheter to improve positioning was not associated with an increase in incidence of thrombus or fibrin sheath formation despite the theoretical risk of a rougher tip that may lead to turbulent venous flow. The suturing of non-tunneled catheters to a patient’s scalp for positioning was found to be uncomfortable for patients and may have resulted in loss of sutures, leading to change in tip position in some cases. Other factors that affected correct tip position included changes in patient size with rapid growth and decrease in edema due to dialysis. Non-tunneled CVCs had higher infection and thrombosis rates, but the difference in thrombosis rate was not statistically different compared to tunneled CVCs per 1000 catheter-days. Both catheter types had a statistically similar rate of IR maintenance procedures.

The retrospective nature and small sample size limited this study. A larger study population would have allowed for multivariate analysis and may have elucidated a possible difference in thrombosis rates between catheter types. The loss of follow-up of 2 patients may also have affected the results. A larger study featuring multiple centers and multivariate analysis may draw more concrete conclusions. In terms of CVC modifications, the authors presented compelling evidence for the need of new catheter options for this population, including more flexible non-tunneled catheter options to allow for thoracic versus cephalic attachment and catheters that eliminate the need to trim the tip to ensure proper tip position.

Post author
Jared Edwards
4th Year Medical Student
Oregon Health & Science University School of Medicine, Portland, OR

Tumor Seeding along the Puncture Tract in CT-Guided Interstitial High-Dose-Rate Brachytherapy

Clinical question

How much tumor seeding occurs from CT guided high dose rate brachytherapy and what are the potential risk factors?

Take away point

Puncture tract tumor seeding is rare following CT-HDRBT.

Reference
Buttner, L., Ludemann, W. M., Jonczyk, M., Denecke, T., Schnapauff, D., Wieners, G., . . . Boning, G. (2020). Tumor Seeding along the Puncture Tract in CT-Guided Interstitial High-Dose-Rate Brachytherapy. J Vasc Interv Radiol, 31(5), 720-727. doi:10.1016/j.jvir.2019.10.006

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Study design
Single-center, retrospective review

Funding source
Research support from the National Cancer Institute and National Institute of Arthritis and Musculoskeletal and Skin Diseases

Setting
Departments of Radiology, Radiooncology, and Radiotherapy
Charité, Universitätsmedizin Berlin, Germany





Figure 3. Examples of tumor seeding.

Summary

CT-guided high-dose-rate brachytherapy (CT-HDRBT) is a local radiotherapy treatment which has shown positives outcomes for the treatment of primary and secondary liver and lung cancers, as well as adrenal, renal, and lymph node tumors. CT-HDRBT involves percutaneously placing a radiation source (iridium-192) into or near a tumor via a catheter and subsequently removing the source after the treatment is complete. CT-HDRBT does not pose the risk of damaging thermosensitive structures and lacks the heat sink effects of other percutaneous ablation techniques. One concern with CT-HDRBT is the lack of post-treatment thermal tract ablation and the potential for tumor seeding. The goal of this study was to quantify tumor seeding after CT-HDBRT and identify potential risk factors.

The authors retrospectively reviewed 1,765 CT-HDRBT treatments in 1,034 patients. The treated tumors included HCC, CRC, and breast cancer in the liver (92.3%), lung (3.9%), and lymph nodes (1.6%). 56.4% of patients received a single treatment, 25.8% received two treatments, and 9.8% received three treatments. 8.2% of patients underwent combined therapy with either TACE, DEB TACE, irinotecan TACE, or TAE. The median follow-up imaging was 15.4 months.

The authors defined tumor tract seeding as tumor cell displacement along a previous catheter or biopsy needle tract. Tumor tract seeding was further classified as outside the treated organ (extraorganic) or inside the treated organ (intraorganic). Only extraorganic tumor seeding was included in this study in order to more precisely differentiate seeding from local recurrence. Tumor seeding was diagnosed based on imaging findings.

Tumor seeding occurred at a median of 8 months and at a rate of 1.5% per intervention, corresponding to a seeding risk of 0.7% per catheter. Tumor seeding most commonly occurred in the context of primary disease progression. Patient age was the only detectable potential risk factor for tumor seeding. Hyper-vascularization may be a risk factor for seeding and patients in this study with hypervascular tumors were treated with CT-HDRBT coupled with either TACE or TAE. While the seeding rate was lower with the combined treatment, the sample size was not large enough to make a definite conclusion. Percutaneous tract irradiation had no effect on tumor seeding occurrence. Cancer type, tumor size, number of catheters used, and previous therapies were not risk factors for tumor seeding.

Commentary

The authors reviewed 1,034 patients with 1,765 CT-HDRBT treatments and displayed a 1.5% overall tumor seeding rate. The study is limited by its retrospective design, the exclusion of intraorganic tumors, and the reliance on imaging diagnosis of tract seeding. The study demonstrated an impressively small tumor seeding rate in an extensive patient population. The 1.5% seeding rate is comparable to the published ranges for other percutaneous ablation procedures. This result is contradictory to the concern that absence of tract ablation raises the risk of seeding. Future studies investigating intraorganic seeding as well as the associated clinical outcomes will be helpful to better understand the risks and clinical impact of tract seeding. Nevertheless, these results suggest that the seeding rate is low and the concern for tumor seeding risk should not discourage treatment in an otherwise ideal candidate.

Post author

Maxwell R. Cretcher, DO
Resident Physician, Integrated Interventional Radiology
Dotter Department of Interventional Radiology
Oregon Health & Science University
@mcretcher