Armeen Mahvash

Kinetic Growth Rate after Portal Vein Embolization Predicts Posthepatectomy Outcomes: Toward Zero Liver-Related Mortality in Patients with Colorectal Liver Metastases and Small Future Liver Remnant

BACKGROUND Standardized future liver remnant (sFLR) volume and degree of hypertrophy after portal vein embolization (PVE) have been recognized as important predictors of surgical outcomes after major liver resection. However, the regeneration rate of the FLR after PVE varies among individuals and its clinical significance is unknown. STUDY DESIGN Kinetic growth rate (KGR) is defined as the degree of hypertrophy at initial volume assessment divided by number of weeks elapsed after PVE. In 107 consecutive patients who underwent liver resection for colorectal liver metastases with an sFLR volume >20%, the ability of the KGR to predict overall and liver-specific postoperative morbidity and mortality was compared with sFLR volume and degree of hypertrophy. RESULTS Using receiver operating characteristic analysis, the best cutoff values for sFLR volume, degree of hypertrophy, and KGR for predicting postoperative hepatic insufficiency were estimated as 29.6%, 7.5%, and 2.0% per week, respectively. Among these, KGR was the most accurate predictor (area under the curve 0.830 [95% CI, 0.736-0.923]; asymptotic significance, 0.002). A KGR of <2% per week vs ≥2% per week correlates with rates of hepatic insufficiency (21.6% vs 0%; p = 0.0001) and liver-related 90-day mortality (8.1% vs 0%; p = 0.04). The predictive value of KGR was not influenced by sFLR volume or the timing of initial volume assessment when evaluated within 8 weeks after PVE. CONCLUSIONS Kinetic growth rate is a better predictor of postoperative morbidity and mortality after liver resection for small FLR than conventional measured volume parameters (ie, sFLR volume and degree of hypertrophy).

Nivolumab for previously treated unresectable metastatic anal cancer (NCI9673): a multicentre, single-arm, phase 2 study

BACKGROUND Squamous cell carcinoma of the anal canal (SCCA) is a rare malignancy associated with infection by human papillomavirus (HPV). No consensus treatment approach exists for the treatment of metastatic disease. Because intratumoral HPV oncoproteins upregulate immune checkpoint proteins such as PD-1 to evade immune-mediated cytotoxicity, we did a trial of the anti-PD-1 antibody nivolumab for patients with metastatic SCCA. METHODS We did this single-arm, multicentre, phase 2 trial at ten academic centres in the USA. We enrolled patients with treatment-refractory metastatic SCCA, who were given nivolumab every 2 weeks (3 mg/kg). The primary endpoint was response according to Response Evaluation Criteria in Solid Tumors, version 1.1, in the intention-to-treat population. At the time of data cutoff, the study was ongoing, with patients continuing to receive treatment. The study is registered with ClinicalTrials.gov, number NCT02314169. RESULTS We screened 39 patients, of whom 37 were enrolled and received at least one dose of nivolumab. Among the 37 patients, nine (24% [95% CI 15-33]) had responses. There were two complete responses and seven partial responses. Grade 3 adverse events were anaemia (n=2), fatigue (n=1), rash (n=1), and hypothyroidism (n=1). No serious adverse events were reported. INTERPRETATION To our knowledge, this is the first completed phase 2 trial of immunotherapy for SCCA. Nivolumab is well tolerated and effective as a monotherapy for patients with metastatic SCCA. Immune checkpoint blockade appears to be a promising approach for patients with this orphan disease. FUNDING National Cancer Institute/Cancer Therapy Evaluation Program, the HPV and Anal Cancer Foundation, the E B Anal Cancer Fund, The University of Texas MD Anderson Moon Shots Program, and an anonymous philanthropic donor.

A marking technique for intraoperative localization of small liver metastases before systemic chemotherapy.

Preoperative chemotherapy is increasingly used prior to resection of colorectal liver metastases (CLM). Since some of these lesions may disappear or may be hardly detectable with intraoperative ultrasound (IOUS), we describe herein a new technique to mark small lesions with coils before chemotherapy. This technique facilitates the resection of small lesions likely to disappear after preoperative chemotherapy.

Partial splenic embolization for cancer patients with thrombocytopenia requiring systemic chemotherapy

Partial splenic embolization (PSE) has been used to improve hematologic parameters related to hypersplenism. The purpose of this study was to review our institutional experience with PSE for cancer patients with thrombocytopenia because of splenic sequestration precluding the administration of systemic therapy (ST).

Temporary Balloon Occlusion of the Common Hepatic Artery for Administration of Yttrium-90 Resin Microspheres in a Patient with Patent Hepatoenteric Collaterals

The most common serious complication of yttrium-90 ((90)Y) therapy is gastrointestinal ulceration caused by extrahepatic microsphere dispersion. The authors describe the use of a balloon catheter for temporary occlusion of the common hepatic artery to reverse hepatoenteric flow for lobar administration of resin microspheres when coil embolization of a retroportal artery was impossible. At 9 months after treatment, the patient had no gastrointestinal side effects and showed a partial response.

Reversible Ureteral Obstruction due to Polyomavirus Infection after Percutaneous Nephrostomy Catheter Placement

BK virus (BKV) is a human polyomavirus that remains latent in the urinary tract epithelium in most individuals. However, in immunocompromised states, including after hematopoietic stem cell transplantation (HSCT), BKV may reactivate and cause infection predominantly affecting the bladder, commonly manifested as hemorrhagic cystitis. Renal insufficiency, occasionally requiring hemodialysis, is not uncommon and was previously attributed to medications or the development of tubulointestitial nephritis. We report a series of 6 HSCT recipients who developed obstructive uropathy of the upper urinary tract system secondary to inflammation and hemorrhage involving the upper uroepithelium, causing ureteral stenosis. Temporary placement of a percutaneous nephrostomy catheter relieved the obstruction and significantly improved kidney function, successfully preventing progression to more advanced renal disease in these patients.

Gastroduodenal artery recanalization after transcatheter fibered coil embolization for prevention of hepaticoenteric flow: incidence and predisposing technical factors in 142 patients.

Background Prophylactic occlusion of extrahepatic vessels prior to radioembolization or chemotherapy infusion is an effective method to prevent gastrointestinal complications. Unfortunately, vascular recanalization can occur. Purpose To retrospectively determine the rate and technical factors associated with gastroduodenal artery (GDA) recanalization after transcatheter occlusion with fibered coils. Material and Methods Patients with hepatic malignancy who underwent fibered coil occlusion of the GDA origin for radioembolization or hepatic arterial chemotherapy infusion with at least one subsequent hepatic angiogram between March 2006 and January 2011 were included. One hundred and forty-two patients (men, 71; women, 71) met study criteria. Hepatic arteriograms were reviewed to determine the frequency of arterial recanalization. Additional parameters included: patients’ demographics, GDA diameter, length of coil pack, distance between GDA origin and most cephalad coil, persistent flow at the conclusion of the initial GDA occlusion procedure, platelet count, and international normalized ratio (INR). Chi-square test and pooled t-test were used to compare the two groups. Prospective multivariate analysis was performed with a logistic regression model. Results Twenty-nine of 142 patients (20.4%) experienced GDA recanalization. The distance between the GDA origin and most cephalad coil was significantly greater in the recanalization group than in the non-recanalization group (9.6 mm vs. 12.6 mm, P = 0.01). A prospective multivariate analysis established that the further the coil was from the origin the more likely the GDA was to recanalize. The two groups did not differ on the basis of any other factors examined. Conclusion GDA origin recanalization after fibered coil occlusion is common. The distance between the GDA origin and most cephalad coil appears to be a predisposing factor for recanalization. Familiarity with this phenomenon is beneficial to reduce the likelihood of gastrointestinal tract complications during hepatic locoregional therapy.

Can imaging patterns of neuroendocrine hepatic metastases predict response yttruim-90 radioembolotherapy?

AIM To evaluate the response to treatment in patients with neuroendocrine tumor liver metastases following yttrium-90 ((90)Y) radioembolotherapy, as a function of image patterns at presentation for (90)Y radioembolotherapy. METHODS The study cohort consisted of patients with hepatic metastatic neuroendocrine tumors treated with (90)Y at our institution during a two-year time period. Hepatic metastases were evaluated on a pre-therapy study assessing relative arterial enhancement compared to liver, lesion size, necrosis of the lesion, and associated tumor burden in the liver. We used six response criteria: Response Evaluation Criteria in Solid Tumors (RECIST) size, World Health Organization (WHO) size, European Association for the Study of the Liver (EASL) necrosis guidelines, Choi size, Choi necrosis and combination of Choi size and necrosis. RESULTS About 65 lesions in 17 patients met study criteria and formed the cohort. Statistically significant response was found for lesions < 5 cm vs those ≥ 5 cm with RECIST (P = 0.04), WHO (P = 0.002) and combined Choi criteria (P = 0.02). Hyperenhancing lesions demonstrated greater response only with the Choi size criteria (P = 0.04). Lesions with ≤ 50% necrosis on the pre-scan had statistically significant greater response with the Choi necrosis criteria (P = 0.01). There was no statistical significance for response comparing lesions < 2 cm vs ≥ 2 cm or in comparing the degrees of tumor burden. CONCLUSION Based on our findings in this study, it is suggested that initial imaging findings, as listed above, are not a good predictor of response to (90)Y radioembolization.

Minimally invasive image-guided therapies for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the fifth most frequently occurring cancer globally and predominantly develops in the setting of various grades of underlying chronic liver disease, which affects management decisions. Image-guided percutaneous ablative or transarterial therapies have acquired wide acceptance in HCC management as a single treatment modality or combined with other treatment options in patients who are not amenable for surgery. Recently, such treatment modalities have also been used for bridging or downsizing before definitive treatment (ie, surgical resection or liver transplantation). This review focuses on the use of minimally invasive image-guided locoregional therapies for HCC. Additionally, it highlights recent advancements in imaging and catheter technology, embolic materials, chemotherapeutic agents, and delivery techniques; all lead to improved patient outcomes, thereby increasing the interest in these invasive techniques.

Hepatocellular Carcinoma Tumor Dose Response After 90Y-radioembolization With Glass Microspheres Using 90Y-SPECT/CT-Based Voxel Dosimetry

PURPOSE To investigate hepatocellular carcinoma tumor dose-response characteristics based on voxel-level absorbed doses (D) and biological effective doses (BED) using quantitative 90Y-single-photon emission computed tomography (SPECT)/computed tomography (CT) after 90Y-radioembilization with glass microspheres. We also investigated the relationship between normal liver D and toxicities. METHODS AND MATERIALS 90Y-radioembolization activity distributions for 34 patients were based on quantitative 90Y-bremsstrahlung SPECT/CT. D maps were generated using a local-deposition algorithm. Contrast-enhanced CT or magnetic resonance imaging scans of the liver were registered to 90Y-SPECT/CT, and all tumors larger than 2.5 cm diameter (53 tumors) were segmented. Tumor mean D and BED (Dmean and BEDmean) and dose volume coverage from 0% to 100% in 10% steps (D0-D100 and BED0-BED100) were extracted. Tumor response was evaluated on follow-up using World Health Organization (WHO), Response Evaluation Criteria in Solid Tumors (RECIST), and modified RECIST (mRECIST) criteria. Differences in dose metrics for responders and nonresponders were assessed using the Mann-Whitney U test. A univariate logistic regression model was used to determine tumor dose metrics that correlated with tumor response. Correlations among tumor size, tumor Dmean, and tumor dose heterogeneity (defined as the coefficient of variation) were assessed. RESULTS The objective response rates were 14 of 53, 15 of 53, and 30 of 53 for WHO, RECIST, and mRECIST criteria, respectively. WHO and RECIST response statuses did not correlate with D or BED. For mRECIST responders and nonresponders, D and BED were significantly different for Dmean, D20 to D80, BEDmean, and BED0 to BED80. Threshold doses (and the 95% confidence interval) for 50% probability of mRECIST response (D50%) were 160 Gy (123-196 Gy) for Dmean and 214 Gy (146-280 Gy) for BEDmean. Tumor dose heterogeneity significantly correlated with tumor volume. No statistically significant association between Dmean to normal liver and complications related to bilirubin, albumin, or ascites was observed. CONCLUSIONS Hepatocellular carcinoma tumor dose-response curves after 90Y-radioembolization with glass microspheres showed Dmean of 160 Gy and BEDmean of 214 Gy for D50% with a positive predictive value of ∼70% and a negative predictive value of ∼62%. No complications were observed in our patient cohort for normal liver Dmean less than 44 Gy.