Ali Habib

Unresectable solitary hepatocellular carcinoma not amenable to radiofrequency ablation: Multicenter radiology-pathology correlation and survival of radiation segmentectomy

Resection and radiofrequency ablation (RFA) are treatment options for hepatocellular carcinoma (HCC) <3 cm; there is interest in expanding the role of ablation to 3‐5 cm. RFA is considered high‐risk when the lesion is in close proximity to critical structures. Combining microcatheter technology and the localized emission properties of Y90, highly selective radioembolization is a possible alternative to RFA in such cases. We assessed the efficacy (response, radiology‐pathology correlation, survival) of radiation segmentectomy in solitary HCC not amenable to RFA or resection. Patients with treatment‐naïve, unresectable, solitary HCC ≤5 cm not amenable to RFA were included in this multicenter study. Administered dose, response rate, time‐to‐progression (modified Response Evaluation Criteria in Solid Tumors [mRECIST]), radiology‐pathology correlation and long‐term survival were assessed. In all, 102 patients were included in this study. mRECIST complete response (CR), partial response (PR), and stable disease (SD) were 47/99 (47%), 39/99 (39%), and 12/99 (12%), respectively. Median time‐to‐disease‐progression was 33.1 months. In all, 33/102 (32%) patients were transplanted with a median (interquartile range [IQR]) time‐to‐transplantation of 6.3 months (3.6‐9.7). Pathology revealed 100% and 50‐99% necrosis in 17/33 (52%) and 16/33 (48%), respectively. Median overall survival was 53.4 months. Univariate analysis demonstrated a survival benefit for Eastern Cooperative Oncology Group (ECOG) 0 patients. In the multivariate model, age <65, ECOG 0, and Child‐Pugh A were characteristics associated with longer survival. Conclusion: Radiation segmentectomy is an effective technique with a favorable risk profile and radiology‐pathology outcomes for solitary HCC ≤5 cm. This approach may allow for treatment of HCC in difficult locations. Since RFA and resection are not options given tumor location, there appears to be a strong rationale for this technique as second choice. (Hepatology 2014;60:192–201)

Prospective randomized pilot study of Y90 +/− sorafenib as bridge to transplantation in hepatocellular carcinoma

BACKGROUND & AIMS To investigate the safety and adverse event profile of sorafenib plus radioembolization (Y90) compared to Y90 alone in patients awaiting liver transplantation. METHODS 20 patients with HCC were randomized to Y90 alone (Group A) or Y90+sorafenib (Group B). Adverse events, dose reductions, and peri-transplant complications were assessed. RESULTS All patients in the sorafenib group necessitated dose reductions. Seventeen of 20 patients underwent liver transplantation; median time-to-transplant was 7.8 months (range: 4.2-20.3) and similar between groups (p = 0.35). In the sorafenib group, there were 4/8 peri-transplant (<30 days) biliary complications (p = 0.029) and 3/8 acute rejections (p = 0.082); there were none in the Y90-only group. Survival rates were 70% (Group A) and 72% (Group B) at 3 years (p = 0.57). CONCLUSIONS The addition of sorafenib to Y90 necessitated dose reductions in all patients awaiting transplantation. Preliminary data suggest that the combination was associated with more peri-transplant biliary complications and potentially trended towards more acute rejections. Caution should be exercised when considering sorafenib in the transplant setting. Further investigation is warranted.

Pretransplant Portal Vein Recanalization-Transjugular Intrahepatic Portosystemic Shunt in Patients With Complete Obliterative Portal Vein Thrombosis.

Background Chronic, obliterative portal vein (PV) thrombosis (PVT) represents a relative contraindication to liver transplantation (LT) in some centers. When PV thromboembolectomy is not feasible, alternative techniques (portacaval hemitransposition, portal arterialization, multivisceral transplantation) are associated with suboptimal outcomes. In cases where a chronically thrombosed PV has become obliterated, we developed PV recanalization (PVR)-transjugular intrahepatic portosystemic shunt (TIPS) to potentiate LT. We evaluated the impact of PVR-TIPS on liver function, transplant eligibility, and long-term outcomes after LT. Methods Forty-four patients with chronic obliterative main PVT were identified during our institutional LT selection committee. After joint imaging review by transplant surgery/radiology, these patients underwent PVR-TIPS to potentiate transplant eligibility. Patients were followed by hepatology/transplant until LT, and ultimately in posttransplant clinic. The TIPS venography and serial ultrasound/MRI were used subsequently to document PV patency. Results The main PV (MPV) was completely thrombosed in 17 of 44 (39%) patients; near complete (>95%) occlusion was noted in 27 of 44 (61%) patients. Direct transhepatic and transsplenic punctures were required in 11 of 43 (26%) and 3 of 43 (7%) cases, respectively. Technical success was 43 of 44 (98%) cases. At PVR-TIPS completion, persistence of MPV thrombus was noted in 33 of 43 (77%) cases. One-month TIPS venography demonstrated complete resolution of MPV thrombosis in 22 of 29 (76%) without anticoagulation. Thirty-six patients were listed for transplantation; 18 (50%) have been transplanted. Eighty-nine percent MPV patency rate and 82% survival were achieved at 5 years. Conclusions The PVR-TIPS may be considered for patients with obliterative PVT who are otherwise appropriate candidates for LT. The high rate of MPV patency post-TIPS placement suggests flow reestablishment as the dominant mechanism of thrombus resolution.

Portal Vein Recanalization–Transjugular Intrahepatic Portosystemic Shunt Using the Transsplenic Approach to Achieve Transplant Candidacy in Patients with Chronic Portal Vein Thrombosis

PURPOSE To present the transsplenic route as an alternative approach for portal vein recanalization-transjugular portosystemic shunt (PVR-TIPS) for chronic main portal vein thrombosis (PVT) in potential transplant candidates. MATERIALS AND METHODS In 2013-2014, 11 consecutive patients with cirrhosis-induced chronic main PVT underwent transsplenic PVR-TIPS. All patients had been denied listing for transplant because of the presence of main PVT, a relative contraindication in this center. The patients were followed for adverse events. Portal vein patency was assessed at 1 month by splenoportography and every 3 months subsequently by ultrasound or magnetic resonance imaging. After PVR-TIPS, patients were reviewed (and subsequently listed for transplant) at a weekly multidisciplinary conference. RESULTS PVR-TIPS using the transsplenic approach was successful in all 11 patients with no major complications. Median age was 61 years (range, 33-67 y) and 9 of 11 patients (82%) were men. Nonalcoholic steatohepatitis was the leading cause of liver disease in 4 of 11 patients (36%), and hepatitis C was present in 4 of 11 patients (36%). Complete main PVT was found in 8 of 11 patients (73%). Of 11 patients, 4 (36%) had a Model for End-Stage Liver Disease score > 18, and 8 (73%) had a baseline Child-Pugh score of 7-10. Minor adverse events occurred in 2 of 11 patients (fever, encephalopathy). At the end of the procedure, 5 of 11 patients (45%) exhibited some minor remaining thrombus in the portal vein; 3 of the 5 patients (60%) had complete thrombus resolution at 1 month, with the remaining 2 patients having resolution at 3 months (no anticoagulation was needed). Three patients underwent successful liver transplant with end-to-end anastomoses. CONCLUSIONS Transsplenic PVR-TIPS is a potentially safe and effective method to treat PVT and improve transplant candidacy.

Minimally invasive transforaminal lumbar interbody fusion: a perspective on current evidence and clinical knowledge.

This paper reviews the current published data regarding open transforaminal lumbar interbody fusion (TLIF) in relation to minimally invasive transforaminal lumbar interbody fusion (MI-TLIF). Introduction. MI-TLIF, a modern method for lumbar interbody arthrodesis, has allowed for a minimally invasive method to treat degenerative spinal pathologies. Currently, there is limited literature that compares TLIF directly to MI-TLIF. Thus, we seek to discuss the current literature on these techniques. Methods. Using a PubMed search, we reviewed recent publications of open and MI-TLIF, dating from 2002 to 2012. We discussed these studies and their findings in this paper, focusing on patient-reported outcomes as well as complications. Results. Data found in 14 articles of the literature was analyzed. Using these reports, we found mean follow-up was 20 months. The mean patient study size was 52. Seven of the articles directly compared outcomes of open TLIF with MI-TLIF, such as mean duration of surgery, length of post-operative stay, blood loss, and complications. Conclusion. Although high-class data comparing these two techniques is lacking, the current evidence supports MI-TLIF with outcomes comparable to that of the traditional, open technique. Further prospective, randomized studies will help to further our understanding of this minimally invasive technique.

Chemoradiation of hepatic malignancies: Prospective, phase 1 study of full-dose capecitabine with escalating doses of yttrium-90 radioembolization

PURPOSE Radiosensitizing chemotherapy improves the outcomes in comparison with radiation alone for gastrointestinal cancers. The delivery of radiation therapy with yttrium90 ((90)Y) radioembolization, in combination with the radiosensitizing chemotherapeutic agent capecitabine, provides the opportunity to enhance the effects of radiation on hepatic malignancies. This phase 1 study sought to determine the maximum tolerated dose (MTD) of (90)Y plus capecitabine in patients with cholangiocarcinoma or liver metastases confined to the liver. METHODS AND MATERIALS Patients were given initial treatment at full-dose capecitabine during days 1 to 14 of a 21-day cycle. At days 1 to 7 of the second cycle, whole-liver (90)Y was given at the test dose, after which time capecitabine was continued. Dose-limiting toxicity (DLT) was determined 6 weeks after (90)Y infusion. If a DLT was not observed, the (90)Y dose was escalated. The planned dose cohorts were 110, 130, 150, and 170 Gy. The primary endpoint was to determine the MTD of (90)Y with full-dose capecitabine. RESULTS Sixteen patients were treated according to the study protocol. Two patients experienced DLTs. Nine patients required capecitabine dose reduction as a result of toxicities attributable to capecitabine alone. The criteria for establishing (90)Y MTD were not met, indicating an MTD of >170 Gy. CONCLUSION The MTD of (90)Y delivered in conjunction with capecitabine in the setting of intrahepatic cholangiocarcinoma or metastatic disease confined to the liver exceeds 170 Gy. This is the highest (90)Y dose reported to date and has important implications on combined therapy with the radiosensitizing oral chemotherapeutic capecitabine. Further studies are under way.

Clinical Outcomes of Microendoscopic Foraminotomy and Decompression in the Cervical Spine

OBJECTIVE Few reports have addressed long-term outcomes, as well as the safety and efficacy of the cervical microendoscopic foraminotomy (CMEF) and cervical microendoscopic diskectomy (CMED) procedures used in modern spine practice to treat degenerative disease of the cervical spine. Accordingly, we present long-term outcomes from a cohort of patients treated for foraminal stenosis or disk herniation with the CMEF or CMED procedure, respectively. METHODS A total of 38 patients were included in the study, with a mean follow-up of 24.47 ± 12.84 months. Patients were monitored prospectively with questionnaires consisting of a visual analog scale for the neck (VASN) and arm (VASA), and a neck disability index (NDI) form. Operative time, estimated blood loss, and hospitalization stay also were collected. Data were analyzed with Microsoft Office Excel 2007. RESULTS The mean 1 year follow-up scores all showed statistically significant improvements: NDI (P = 0.0019), VASN (P = 0.0017), VASA (P ≤ 0.0001). Similar results were seen at 2-year follow-up: NDI (P = 0.0011), VASN (P = 0.0022), and VASA (P ≤ 0.0001); and at 3- to 6-year follow-up: NDI (P = 0.0015), VASN (P = 0.0200), and VASA (P = 0.0034). The average operation time, hospitalization stay, and estimated blood loss were 154.27 ± 26.79 minutes, 21.22 ± 14.23 hours, and 27.92 mL, respectively. There were no statistically significant differences when patients were compared by age (over 50 vs. under 50), operative level (above C6 vs. below C6), or sex. One complication was reported in this study consisting of duratomy, which required no further intervention. CONCLUSION Posterior CMEF and CMED are safe and effective procedures for minimally invasive decompression in the cervical spine.

Locoregional Therapy of Hepatocellular Carcinoma

Hepatocellular carcinoma can be treated using minimally invasive, image-guided, catheter-based or percutaneous techniques. Such procedures offer compelling clinical outcomes with a favorable side-effect profile in a population of patients who are poor candidates for surgical or systemic treatment. This article discusses key data regarding the effectiveness of locoregional therapies in treating these patients. Disease-specific treatment is discussed in the context of hepatocellular carcinoma, with additional data discussed in the context of transplantation. As rapid innovation occurs in the realm of oncology, interventional oncology represents a safe, effective alternative that continues to generate impressive data that could potentially change treatment paradigms.

Institutional decision to adopt Y90 as primary treatment for hepatocellular carcinoma informed by a 1,000-patient 15-year experience

Yttrium‐90 transarterial radioembolization (TARE) is a locoregional therapy (LRT) for hepatocellular carcinoma (HCC). In this study, we present overall survival (OS) outcomes in a 1,000‐patient cohort acquired over a 15‐year period. Between December 1, 2003 and March 31, 2017, 1,000 patients with HCC were treated with TARE as part of a prospective cohort study. A comprehensive review of toxicity and survival outcomes was performed. Outcomes were stratified by baseline Child‐Pugh (CP) class, United Network for Organ Sharing (UNOS), and Barcelona Clinic Liver Cancer (BCLC) staging systems. Albumin and bilirubin laboratory toxicities were compared to baseline. OS outcomes were reported using censoring and intention‐to‐treat methodologies. All treatments were outpatient, with a median one treatment per patient. Five hundred six (51%) were CP A, 450 (45%) CP B, and 44 (4%) CP C. Two hundred sixty‐three (26%) patients were BCLC A, 152 (15%) B, 541 (54%) C, and 44 (4%) D. Three hundred sixty‐eight (37%) were UNOS T1/T2, 169 (17%) T3, 147 (15%) T4a, 223 (22%) T4b, and 93 (9%) N/M. In CP A patients, censored OS for BCLC A was 47.3 (confidence interval [CI], 39.5‐80.3) months, BCLC B 25.0 (CI, 17.3‐30.5) months, and BCLC C 15.0 (CI, 13.8‐17.7) months. In CP B patients, censored OS for BCLC A was 27 (CI, 21‐30.2) months, BCLC B 15.0 (CI, 12.3‐19.0) months, and BCLC C 8.0 (CI, 6.8‐9.5) months. Forty‐nine (5%) and 110 (11%) patients developed grade 3/4 albumin and bilirubin toxicities, respectively. Conclusion: Based on our experience with 1,000 patients over 15 years, we have made a decision to adopt TARE as the first‐line transarterial LRT for patients with HCC. Our decision was informed by prospective data and incrementally reported demonstrating outcomes stratified by BCLC, applied as either neoadjuvant or definitive treatment. (Hepatology 2017).

Plasminogen activator inhibitor-1 in sputum and nasal lavage fluids increases in asthmatic patients during common colds.

This study showed that sputum and nasal lavage levels of plasminogen activator inhibitor-1 (PAI-1) rise during a common cold in asthmatic patients. This rise may contribute to the progression of airway remodeling.