Are radiological endpoints surrogate outcomes of overall survival in hepatocellular carcinoma treated with transarterial chemoembolization?

BACKGROUND& AIMS: Time to progression (TTP) and progression-free survival (PFS) are commonly used as surrogate endpoints in oncology trials. We aimed to assess the surrogacy relationship of TTP and PFS with overall survival (OS) in studies of transarterial chemoembolization (TACE) for unresectable hepatocellular carcinoma (u-HCC) by innovative methods. METHODS: A search of databases for studies of TACE for u-HCC reporting both OS and TTP or PFS was performed. Individual patient data were extracted from TTP/PFS and OS Kaplan-Meier curves of TACE arms. Pooled median TTP and OS were obtained from random-effect model. The surrogate relationships of hazard ratios (HRs) and median TTP for OS were evaluated by the coefficient of determination R2 . RESULTS: We identified 13 studies comparing TACE vs systemic therapy or vs TACE plus systemic therapy and including 1932 TACE-treated patients. Pooled median OS was 11.2 months (95% confidence interval [95%CI] 7.9-17.8), and pooled median TTP was 5.4 months (95%CI 3.8-8.0). Heterogeneity among studies was highly significant for both outcomes. The correlation between HR TTP and HR OS was moderate (R2  = 0.65. 95%CI 0.08-0.81). R2 value was 0.04 (95%CI 0.00-0.35) between median TTP and median OS. CONCLUSION: In studies of TACE for u-HCC, the surrogate relationship of radiology-based endpoints with OS is moderate. Multiple endpoints including hepatic decompensation, macrovascular invasion and extrahepatic spread are needed for future trials comparing systemic therapies or combination of TACE with systemic therapies vs TACE alone.

Mirizzi syndrome type V complicated with both cholecystobiliary and cholecystocolic fistula: a case report.

Mirizzi syndrome (MS) is a common bile duct (CBD) obstruction caused by extrinsic compression from an impacted stone in the cystic duct or infundibulum of the gallbladder. Patients affected by MS may present abdominal pain and jaundice. A 37-year-old male with neurologic residuals post-encephalitis arrived at the emergency department reporting abdominal pain, jaundice and fever. An ultrasound of the abdomen identified cholecystolithiasis with a dilated CBD. He did not undergo CT or MRI due to poor compliance and parents' disagreement. Eventually, they accepted to perform endoscopic retrograde cholangiopancreatography, which diagnosed MS with both cholecystobiliary and cholecystocolonic fistula without gallstone ileum (type Va). Therefore, patient underwent cholecystectomy, wedge resection of the colon and choledochoplasty with 'Kehr's T-tube' insertion. A plastic biliary stent was successively placed and removed after 4 month. Ultimately, he did neither complain any other biliary symptoms nor alteration in laboratory tests after 4-years of follow-up.

Mirizzi syndrome in a patient with partial gastrectomy with Billroth II anastomosis: A case report.

INTRODUCTION: Mirizzi Syndrome (MS) is a common bile duct (CBD) obstruction caused by extrinsic compression from an impacted stone in the cystic duct or infundibulum of the gallbladder. Radiological evaluation may mistake it for CBD stones in jaundiced patient, especially in those who have altered anatomy of upper gastrointestinal (e.g. sub-total gastrectomy - STG - with Billroth I or II anastomosis). PRESENTATION OF CASE: A 69-year-old male with a history of STG Billroth-II 25 years prior, accessed hospital for abdominal pain and jaundice with increasing in hepatic laboratory tests. Ultrasound of abdomen, CT scan and MRCP diagnosed CBD stones, so endoscopic retrograde cholangiopancreatography (ERCP) was performed, using a gastroscope to reach papillary region and to achieve cannulation of biliary duct. During cholangiography patient resulted affected by Mirizzi syndrome type I, so laparoscopic cholecystectomy was performed and cystic duct was moved away. DISCUSSION: This rare case shows how it's easy to delay the correct treatment when a wrong radiological diagnosis is made. Moreover, ERCP remains a challenging procedure in patients with altered anatomy, such as STG B-II, and in this case gastroscope was needed for cannulation, due to the need of frontal view. CONCLUSION: This rare case report highlights the importance of not forgetting MS in the differential diagnosis of biliary obstruction, especially in those patients with upper GI altered anatomy. Physicians with expertise in ERCP should always consider altered anatomy as a factor which may confuse radiologist in diagnosis, so in this case MS may be discovered or confirmed at ERCP.

An evaluation score of the difficulty of thyroidectomy considering operating time and preservation of recurrent laryngeal nerve.

The purpose of this study was to edit a renovated thyroidectomy difficulty scale (rTDS) in order to identify underlying thyroid diseases with a longer operative time and higher technical difficulty, also considering preservation of recurrent laryngeal nerve. We developed a renovated scale with a maximum score of 20 points by creating a form in which five variables were considered: vascularity, friability, mobility/fibrosis, gland size and difficulty in preservation of the recurrent laryngeal nerve. Two surgeons separately evaluated each of these. Through a simple linear regression analysis, we have analyzed the relationship between rTDS score and operative times, and between rTDS score and preservation of recurrent nerve. Eventually, Spearman's rank correlation coefficient has been used in order to evaluate our double-blind study. Our cohort included 131 patients undergoing total thyroidectomy. The mean of the rTDS was 9.00 ± 3.67 for Surgeon A and 8.31 ± 3.42 for Surgeon B, with Spearman's rank correlation coefficient between surgeons of 0.85 (p < 0.0001). We have shown that the rTDS score significantly influences the operating times (R2 = 0.44 for surgeon A, R2 = 0.46 for B, p < 0.0001 for both). Moreover, we can say that the rTDS score significantly influences preservation of the recurrent nerve (R2 = 0.37, Beta 0.61, 8.84 t test, p < 0.0001). Our rTDS is a useful tool and, thanks to it, we identified hyperthyroidism and goiter as the hardest underlying disease for surgery. Thus our scale could change operative approach, resulting in better surgeries' scheduling and identification of pathologies that require higher attention.