Multicentre study of liver metastases from colorectal cancer in pathological livers

AbstractObjectivesResection of colorectal cancer (CRC) liver metastases (LM) in pathological liver (PL) patients (with cirrhosis or hepatopathy) is extremely rare. The aim of this study was to perform a multicentre, retrospective analysis of epidemiology, surgical techniques and outcomes in patients with PL who underwent hepatic resection for CRC-LM.MethodsA retrospective, multicentre questionnaire was distributed to 15 hepatopancreatobiliary surgical units.ResultsOnly six of 15 (40%) HPB units reported any experience in the surgical resection of CRC-LM in patients with PL. Of the 20 patients identified, 10 had underlying cirrhosis and 10 had chronic hepatopathy. Their median age was 66 years (range: 49–81 years). Thirteen patients were male. Liver dysfunction was known preoperatively in 18 patients. All patients had Child–Pugh class A disease. Six patients had synchronous disease. There were a total of 38 lesions among the 20 patients, distributed at a median of one lesion per patient (range: 1–4 lesions). The median size of the lesions was 3.0cm (range: 1.5–9.0cm). Preoperative median carcinoembryonic antigen (CEA) was 32.3ng/ml (range: 1–184ng/ml). The surgical procedures performed included: sub-segmentectomy (n= 12); left lateral sectionectomy (n= 6); segmentectomy (n= 4); radiofrequency ablation (n= 3), and exploratory laparotomy (n= 4). Morbidity occurred in four patients (Clavien grades I [n= 1], II [n= 2] and IVa [n= 1]). Mortality was nil. An R0 resection margin was achieved in 15 of 16 patients. Twelve patients did not receive chemotherapy. In resected patients, 10 presented with relapse. The median disease-free and overall survival periods were 12.2 and 22.3 months, respectively.ConclusionsWhen feasible, liver resection is the best option for CRC-LM in PL patients

Unpredicted Aberrant Splicing Products Identified in Postmortem Sudden Cardiac Death Samples

Molecular screening for pathogenic mutations in sudden cardiac death (SCD)-related genes is common practice for SCD cases. However, test results may lead to uncertainty because of the identification of variants of unknown significance (VUS) occurring in up to 70% of total identified variants due to a lack of experimental studies. Genetic variants affecting potential splice site variants are among the most difficult to interpret. The aim of this study was to examine rare intronic variants identified in the exonic flanking sequence to meet two main objectives: first, to validate that canonical intronic variants produce aberrant splicing; second, to determine whether rare intronic variants predicted as VUS may affect the splicing product. To achieve these objectives, 28 heart samples of cases of SCD carrying rare intronic variants were studied. Samples were analyzed using 85 SCD genes in custom panel sequencing. Our results showed that rare intronic variants affecting the most canonical splice sites displayed in 100% of cases that they would affect the splicing product, possibly causing aberrant isoforms. However, 25% of these cases (1/4) showed normal splicing, contradicting the in silico results. On the contrary, in silico results predicted an effect in 0% of cases, and experimental results showed >20% (3/14) unpredicted aberrant splicing. Thus, deep intron variants are likely predicted to not have an effect, which, based on our results, might be an underestimation of their effect and, therefore, of their pathogenicity classification and family members’ follow-up

Extra-Glissonian approach in liver resection

AbstractBackgroundIn this study we analyzed our most recent experience in the use of the extraglissonian approach to the hilar structures in two circumstances: pedicle transection during major liver resections, and selective clamping in minor hepatectomies.MethodsThe major liver resections study group consisted of 89 cases. Extraglissonian approach and stapler transection of hilar structures was used in 61 (69%). The study group of minor liver resections consisted of 103 cases. Extraglissonian approach and selective clamping was used in 27 cases (26%).ResultsIn major hepatectomies pedicle stapling and hilar dissection demonstrated a similar operative time (240 vs. 260 min; P=0.230); no differences were observed in the amount of haemorrhage (800ml vs. 730ml; P=0.699), number of patients transfused (16 vs. 6; P=0.418) and volume of blood transfused (4 PRC vs. 4 PRC; P=0.521). Duration of vascular pedicle occlusion was 35 vs. 30 min respectively (P=0.293). Major complications (grade ≥3a) occurred in 18 (20%) patients and mortality rates (4.9% vs. 3.5%; P=0.882) were similar for both group. In minor liver resections there were no differences between Pringle and selective clamping in operative time (240 vs. 240 min; P=0.321), haemorrhage (435ml vs. 310ml; P=0.575), number of patients transfused (18 vs. 7; P=0.505) and volume blood transfused (4 PRC vs. 3 PRC; P=0.423). Major complications (grade ≥3a) occurred in 14 (14%) patients, and mortality (2.6% vs. 3.7%; P=0.719) were similar for both groups. However, the duration of pedicle clamping was significantly longer in the selective clamping group (26±21 minutes vs. 44±18 minutes) (P=0.001).ConclusionsThe extraglissonian approach can be extremely useful in liver surgery. Selective clamping with extraglissonian approach avoids ischemia to the other hemiliver. Selective clamping it is also important from the homodynamic point of view because there is no splanchnic stasis and low fluid replacement

Does the Artery-first Approach Improve the Rate of R0 Resection in Pancreatoduodenectomy? A Multicenter, Randomized, Controlled Trial

[Objective]: To compare the rates of R0 resection in pancreatoduodenectomy (PD) for pancreatic and periampullary malignant tumors by means of standard (ST-PD) versus artery-first approach (AFA-PD). [Background]: Standardized histological examination of PD specimens has shown that most pancreatic resections thought to be R0 resections are R1. “Artery-first approach” is a surgical technique characterized by meticulous dissection of arterial planes and clearing of retropancreatic tissue in an attempt to achieve a higher rate of R0. To date, studies comparing AFA-PD versus ST-PD are retrospective cohort or case-control studies. [Methods]: A multicenter, randomized, controlled trial was conducted in 10 University Hospitals (NCT02803814, ClinicalTrials.gov). Eligible patients were those who presented with pancreatic head adenocarcinoma and periampullary tumors (ampulloma, distal cholangiocarcinoma, duodenal adenocarcinoma). Assignment to each group (ST-PD or AFA-PD) was randomized by blocks and stratified by centers. The primary end-point was the rate of tumor-free resection margins (R0); secondary end-points were postoperative complications and mortality. [Results]: One hundred seventy-nine patients were assessed for eligibility and 176 randomized. After exclusions, the final analysis included 75 ST-PD and 78 AFA-PD. R0 resection rates were 77.3% (95% CI: 68.4–87.4) with ST-PD and 67.9% (95% CI: 58.3–79.1) with AFA-PD, P=0.194. There were no significant differences in postoperative complication rates, overall 73.3% versus 67.9%, and perioperative mortality 4% versus 6.4%. [Conclusions]: Despite theoretical oncological advantages associated with AFA-PD and evidence coming from low-level studies, this multicenter, randomized, controlled trial has found no difference neither in R0 resection rates nor in postoperative complications in patients undergoing ST-PD versus AFA-PD for pancreatic head adenocarcinoma and other periampullary tumors