The effect of trans arterial chemoembolization in the management of intrahepatic cholangiocarcinoma. A systematic review and meta-analysis

BackgroundA comprehensive re-evaluation on the role of trans-arterial chemoembolization (TACE) in patients with intrahepatic cholangiocarcinoma.MethodsA thorough database searching was performed in PubMed, EMBASE, and the Cochrane Library. Eligible studies were restricted to comparative studies between TACE and non-TACE cohorts. RevMan5.3 software and Stata 13.0 software were used for statistical analyses. The primary endpoint of our study was long-term survival.ResultsA total of 11 studies with 2036 patients were finally identified. Pooled results revealed that patients receiving TACE had a significantly better overall survival (OS) versus those without TACE (P < 0.05). Subgroup analyses were performed according to different types of TACE. Prophylactic post-surgical TACE (PPTACE) was associated with a significantly better OS versus those without PPTACE (P < 0.05). Palliative TACE (PTACE) also achieved a significantly better OS compared with those with supportive treatment (ST) only (P < 0.00001). However, TACE had no impact on disease-free survival (P = 0.87) and was less effective than surgical resection (P = 0.003).ConclusionPPTACE has a remarkable impact on OS versus those with surgical resections only and should be regularly performed. Regarding patients with unresectable disease, apart from conventional ST, adjuvant PTACE is also recommended. Upcoming prospective randomized controlled trials are warranted for further validation.     

Metastasis-directed Therapy in Prostate Cancer: Prognostic Significance of the ESTRO/EORTC Classification in Oligometastatic Bone Disease

AimsOligometastatic disease (OMD) represents a spectrum of clinical scenarios and various classification systems have been proposed. Bone-only OMD can occur in patients with advanced prostate cancer and validated decision-making tools are needed to assist patient selection for metastasis-directed therapy. The aim of the present study was to determine the prognostic utility of a classification system for OMD.Materials and methodsA retrospective review was conducted of all patients with bone-only oligometastatic prostate cancer treated with stereotactic body radiotherapy (SBRT) since November 2011. SBRT was delivered using CyberKnife® and gantry-based linear accelerator platforms. All patients were classified into oligometastatic states based on the European Society for Radiotherapy and Oncology/European Organisation for Research and Treatment of Cancer (ESTRO/EORTC) classification system. Kaplan–Meier and Cox regression analyses were carried out to determine the prognostic utility of this classification system.ResultsIn total, 105 patients with 145 osseous metastases were treated over 119 sessions. The median follow-up after SBRT was 23 months (interquartile range 10–39.8). Twelve patients had died after a median time of 31 months. The 3-year metastatic progression-free survival was 23% (95% confidence interval 13–32) and the 3-year overall survival was 88% (95% confidence interval 80–96). Patients in a metachronous oligometastatic state were 4.50 (95% confidence interval 1.19–17.10, P = 0.03) times more likely to experience metastatic progression compared with those with synchronous oligometastases, and 6.69 (95% confidence interval 1.05–42.50, P = 0.04) times more likely to experience any failure. Hazard ratio magnitudes increased for patients in a repeat oligometastatic state. The multivariate model for both metastatic progression-free survival and failure-free survival found prostate-specific antigen doubling time <4 months (P = 0.002; P = 0.05) to independently predict for progression.ConclusionThe ESTRO/EORTC classification of OMD predicts for progression in patients treated with SBRT for bone-only oligometastatic prostate cancer at our institution. Further validation in prospective series over multiple tumour sites is needed. These characterisation factors should be assessed in patients considered for metastasis-directed therapy together with established prognostic features.     

Efficacy and safety of transjugular intrahepatic portosystemic shunt (TIPS) created using covered stents of different diameters: A systematic review and meta-analysis

PurposeThe purpose of this study was to make a systematic review and meta-analysis to determine the stent diameter (8 mm vs. 10 mm) that conveys better safety and clinical efficacy for transjugular intrahepatic portosystemic shunt (TIPS).Materials and methodsFour databases were used to identify clinical trials published from inception until March 2020. Data were extracted to estimate and compare one-year and three-year overall survivals, hepatic encephalopathy, variceal rebleeding, and shunt dysfunction rates between patients with 8 mm covered stents and those with 10 mm covered stents.ResultsFive eligible studies were selected, which included 489 patients (316 men, 173 women). The 8 mm covered stent group had higher efficacy regarding one-year or three-year overall survival (odds ratio [OR], 2.88; P = 0.003) and (OR, 1.81; P = 0.04) and lower hepatic encephalopathy (OR, 0.69; P = 0.04) compared with 10 mm covered stent group. There were no significant differences in variceal rebleeding rate (OR 0.80; P = 0.67). However, shunt dysfunction was lower in 10 mm covered stent group (OR, 2.26; P = 0.003).ConclusionsOur results suggest that the use of 8 mm covered stents should be preferred to that of 10 mm covered stents for TIPS placement when portal pressure is frequently monitored.     

Immunotherapy as Single Treatment for Patients With NSCLC With Brain Metastases: A Systematic Review and Meta-Analysis—the META-L-BRAIN Study

IntroductionBrain metastases (BMs) occur in 40% of patients with lung cancer. The activity of immunotherapy in these patients, however, remains controversial, as the cornerstone treatment is radiotherapy (RT). Because RT is associated with adverse events that may impair the quality of life, the possibility of substituting it with a single systemic approach is attractive. Therefore, we performed a systematic review and meta-analysis to evaluate the potential benefit of immune checkpoint inhibitors (ICIs) in patients with NSCLC with untreated BM (unBM).MethodsStudies that enrolled patients with NSCLC treated with ICIs and specifically allowed for unBM were identified by searching the EMBASE, PubMed, Cochrane, and other databases. The outcomes evaluated were intracerebral overall response rate (icORR) and intracerebral disease control rate (icDCR) for unBM, and grades 3 and 4 toxicity rate.ResultsWe included 12 studies with a total of 566 individuals in the final analysis. Anti–programmed cell death protein-1 therapy seems to be active in the central nervous system, with an icORR of 16.4% (95% confidence interval [CI]: 9.8%–24%; I² = 33.17%) and an icDCR of 45% (95% CI: 33.4%–56.9%; I² = 46.91%). In the meta-analysis for icORR (risk ratio = 1.26, 95% CI: 0.57–2.79) and icDCR (risk ratio = 0.88, 95% CI: 0.55–1.43) we did not observe any difference among patients with BM who were treated with RT before ICI start and those who were treated with ICI only.ConclusionsICI seems to be effective as a single treatment for active BM in selected patients with advanced NSCLC.     

A Pre-implementation Study of Volumetric Modulated Arc Therapy for Same-day Planning and Treatment of Vertebral Bone Metastases Within a Rapid-access Palliative Radiotherapy Programme

AimsWe aimed to develop a process for same-day contouring, planning, quality assurance and delivery of volumetric modulated arc therapy (VMAT) for vertebral bone metastases within our institution's rapid-access palliative radiotherapy programme.Materials and methodsTwo thoracic (T6–7, T3–7) and two lumbar (L2–3, L1–5) targets were contoured on computed tomography images acquired from an anthropomorphic phantom and five patient scans. Inverse planning aimed to provide coverage of a prescribed dose of 8 Gy with a combined lung V2Gy < 25% and a combined kidney mean dose <2 Gy. Serial plans were created to identify an efficient combination of six main planning variables specific to our treatment planning system: (i) voxel size (3 mm versus 5 mm), (ii) Monte Carlo statistical uncertainty (1% per calculation versus 3% per control point), (iii) fluence smoothing (medium versus high), (iv) number of iterations of segment shape changes during optimisation (1 versus 5), (v) dose calculation algorithm (Monte Carlo versus pencil beam) and (vi) number of arcs (single versus multiple). Contouring, planning, quality assurance and treatment delivery were timed.ResultsThe combination of planning variables deemed efficient and appropriate was: a 3 mm voxel size, statistical uncertainty of 1% per calculation, medium fluence smoothing, five iterations of segment shape changes, Monte Carlo dose calculation and single full arc delivery. Patient scan contouring times ranged from 7 to 9 min (T6–7), 11–13 min (T3–7), 5–7 min (L2–3) and 8–10 min (L1–5) and planning times ranged from 9 to 15 min (T6–7), 13–25 min (T3–7), 18–25 min (L2–3) and 21–31 min (L1–5). Physics quality assurance times ranged from 15 to 21 min and beam-on times ranged from 3 to 6 min.ConclusionsThe combined elements of VMAT for thoracic and lumbar vertebral bone metastases were completed in under 2 h. This new process makes same-day contouring, planning, quality assurance and treatment delivery of VMAT feasible within our rapid-access palliative radiotherapy programme.     

The impact of PRODIGE 7 on the current worldwide practice of CRS-HIPEC for colorectal peritoneal metastases: A web-based survey and 2021 statement by Peritoneal Surface Oncology Group International (PSOGI)

IntroductionThe PRODIGE 7-trial investigated the additional value of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) to cytoreductive surgery (CRS) for patients with colorectal peritoneal metastases (CPM). The results of PRODIGE 7 were presented at the 2018 ASCO meeting showing that 30 min oxaliplatin-based HIPEC did not improve overall survival. The current study investigated the impact of PRODIGE 7 on the worldwide practice of CRS and HIPEC.Materials and methodsCRS-HIPEC experts from 19 countries were invited through the Peritoneal Surface Oncology Group International (PSOGI) to complete an online survey concerning the current CRS-HIPEC practice in their hospital and country, and were asked to appraise the effect of PRODIGE 7.ResultsThe survey was completed by 18/19 experts. Although their personal opinions of CRS-HIPEC were barely influenced by PRODIGE 7, they reported a substantial impact on daily practice. This included a switch towards Mitomycin-C based HIPEC-regimens and prolongation of HIPEC perfusion time, a reduction in the number of referrals from non-HIPEC centers, a reduction in national consensus, the removal of HIPEC from national guidelines, and a reduced reimbursement rate.ConclusionThe PRODIGE 7 has had a major impact on the practice of CRS-HIPEC for CPM worldwide. HIPEC remains an attractive option with potential for control and eradication of disease and further studies into the optimal HIPEC-regimen are urgently needed. Meanwhile, given the complexity of the treatment of patients with CPM, and the proven benefits of optimal CRS, referral of patients with potentially resectable CPM to expert centers is recommended whilst the precise role of HIPEC is further evaluated.     

Successful management and technical aspects of major liver resection in children: A retrospective cohort study

Optimal treatment of patients with various types of liver tumors or certain liver diseases frequently demands major liver resection, which remains a clinical challenge especially in children.Eighty seven consecutive pediatric liver resections including 51 (59%) major resections (resection of 3 or more hepatic segments) and 36 (41%) minor resections (resection of 1 or 2 segments) were analyzed. All patients were treated between January 2010 and March 2018. Perioperative outcomes were compared between major and minor hepatic resections.The male to female ratio was 1.72:1. The median age at operation was 20 months (range, 0.33–150 months). There was no significant difference in demographics including age, weight, ASA class, and underlying pathology. The surgical management included functional assessment of the future liver remnant, critical perioperative management, enhanced understanding of hepatic segmental anatomy, and bleeding control, as well as refined surgical techniques. The median estimated blood loss was 40 ml in the minor liver resection group, and 90 ml in major liver resection group (P < .001). Children undergoing major liver resection had a significantly longer median operative time (80 vs 140 minutes), anesthesia time (140 vs 205 minutes), as well as higher median intraoperative total fluid input (255 vs 450 ml) (P < .001 for all). Fourteen (16.1%) patients had postoperative complications. By Clavien-Dindo classification, there were 8 grade I, 4 grade II, and 2 grade III-a complications. There were no significant differences in complication rates between groups (P = .902). Time to clear liquid diet (P = .381) and general diet (P = .473) was not significantly different. There was no difference in hospital length of stay (7 vs 7 days, P = .450). There were no 90-day readmissions or mortalities.Major liver resection in children is not associated with an increased incidence of postoperative complications or prolonged postoperative hospital stay compared to minor liver resection. Techniques employed in this study offered good perioperative outcomes for children undergoing major liver resections.     

Diagnostic approach to well-differentiated hepatocellular carcinoma

Well-differentiated hepatocellular mass-lesions in non-cirrhotic livers have a differential diagnosis of focal nodular hyperplasia, regenerative hepatic pseudotumors, hepatic adenoma, hepatocellular carcinoma, and fibrolamellar carcinoma. Despite significant advances in characterizing these pseudotumors and tumors, they remain a diagnostic challenge, especially on needle biopsy. This review focuses on a systematic diagnostic approach, one that allows confident diagnosis of these lesions.     

Efficacy and Safety of Transjugular Intrahepatic Portosystemic Shunt Creation for Budd-Chiari Syndrome: A Systematic Review and Meta-Analysis

PurposeTo assess the critical role of transjugular intrahepatic portosystemic shunt (TIPS) in the management of Budd-Chiari syndrome (BCS), as the data with respect to the safety and outcome of TIPS in patients with BCS are scarce because of the rarity of the disease.Materials and MethodsA comprehensive search of literature of various databases from 2000 to October 2021 was conducted for studies evaluating the outcome of TIPS in patients with BCS. The primary outcomes of the analysis were technical and clinical success, adverse events and mortality associated with TIPS, dysfunction of TIPS, need for TIPS revision, need for liver transplantation (LT), and 1-year survival.ResultsA total of 33 studies (1,395 patients) were included in this meta-analysis. The pooled rates and 95% confidence intervals of various outcomes were 98.6% (97.6–99.7) for technical success, 90.3% (86.0–94.6) for clinical success, 10.0% (6.5–13.6) for major adverse events, 0.5% (0.2–1.0) for TIPS-related mortality, 11.6% (7.8–15.4) for post-TIPS hepatic encephalopathy (HE), 40.1% (32.5–47.7) for TIPS dysfunction, 8.6% (4.9–12.4) for the need for TIPS revision, 4.5% (2.8–6.2) for the need for LT, and 94.6% (93.1–96.1) for 1-year survival. Publication bias was seen with all outcomes except for post-TIPS HE, TIPS dysfunction, and the need for LT.ConclusionsThe existing literature supports the feasibility, safety, and efficacy of TIPS in the treatment of BCS. Deciding the optimal timing of TIPS in BCS needs further studies.