RAS mutation status predicts survival and patterns of recurrence in patients undergoing hepatectomy for colorectal liver metastases.

ObjectiveTo determine the impact of RAS mutation status on survival and patterns of recurrence in patients undergoing curative resection of colorectal liver metastases (CLM) after preoperative modern chemotherapy.BackgroundRAS mutation has been reported to be associated with aggressive tumor biology. However, the effect of RAS mutation on survival and patterns of recurrence after resection of CLM remains unclear.MethodsSomatic mutations were analyzed using mass spectroscopy in 193 patients who underwent single-regimen modern chemotherapy before resection of CLM. The relationship between RAS mutation status and survival outcomes was investigated.ResultsDetected somatic mutations included RAS (KRAS/NRAS) in 34 (18%), PIK3CA in 13 (7%), and BRAF in 2 (1%) patients. At a median follow-up of 33 months, 3-year overall survival (OS) rates were 81% in patients with wild-type versus 52.2% in patients with mutant RAS (P = 0.002); 3-year recurrence-free survival (RFS) rates were 33.5% with wild-type versus 13.5% with mutant RAS (P = 0.001). Liver and lung recurrences were observed in 89 and 83 patients, respectively. Patients with RAS mutation had a lower 3-year lung RFS rate (34.6% vs 59.3%, P < 0.001) but not a lower 3-year liver RFS rate (43.8% vs 50.2%, P = 0.181). In multivariate analyses, RAS mutation predicted worse OS [hazard ratio (HR) = 2.3, P = 0.002), overall RFS (HR = 1.9, P = 0.005), and lung RFS (HR = 2.0, P = 0.01), but not liver RFS (P = 0.181).ConclusionsRAS mutation predicts early lung recurrence and worse survival after curative resection of CLM. This information may be used to individualize systemic and local tumor-directed therapies and follow-up strategies

Current Role of Minimally Invasive Radical Cholecystectomy for Gallbladder Cancer

Background. For Tis and T1a gallbladder cancer (GbC), laparoscopic cholecystectomy can provide similar survival outcomes compared to open cholecystectomy. However, for patients affected by resectable T1b or more advanced GbC, open approach radical cholecystectomy (RC), consisting in gallbladder liver bed resection or segment 4b-5 bisegmentectomy, with locoregional lymphadenectomy, is considered the gold standard while minimally invasive RC (MiRC) is skeptically considered. Aim. To analyze current literature on perioperative and oncologic outcomes of MiRC for patients affected by GbC. Methods. A Medline review of published articles until June 2016 concerning MiRC for GbC was performed. Results. Data relevant for this review were presented in 13 articles, including 152 patients undergoing an attempt of MiRC for GbC. No randomized clinical trial was found. The approach was laparoscopic in 147 patients and robotic in five. Conversion was required in 15 (10%) patients. Postoperative complications rate was 10% with no mortality. Long-term survival outcomes were reported by 11 studies, two of them showing similar oncologic results when comparing MiRC with matched open RC. Conclusions. Although randomized clinical trials are still lacking and only descriptive studies reporting on limited number of patients are available, current literature seems suggesting that when performed at highly specialized centers, MiRC for GbC is safe and feasible and has oncologic outcomes comparable to open RC

Global survey on the surgical management of patients affected by colorectal cancer with synchronous liver metastases: impact of surgical specialty and geographic region

BACKGROUND: Consensus on the best surgical strategy for the management of synchronous colorectal liver metastases (sCRLM) has not been achieved. This study aimed to assess the attitudes of surgeons involved in the treatment of sCRLM. METHODS: Surveys designed for colorectal, hepato-pancreato-biliary (HPB), and general surgeons were disseminated through representative societies. Subgroup analyses were performed to compare responses between specialties and continents. RESULTS: Overall, 270 surgeons (57 colorectal, 100 HPB and 113 general surgeons) responded. Specialist surgeons more frequently utilized minimally invasive surgery (MIS) than general surgeons for colon (94.8% vs. 71.7%, p < 0.001), rectal (91.2% vs. 64.6%, p < 0.001), and liver resections (53% vs. 34.5%, p = 0.005). In patients with an asymptomatic primary, the liver-first two-stage approach was preferred in most respondents' centres (59.3%), while the colorectal-first approach was preferred in Oceania (83.3%) and Asia (63.4%). A substantial proportion of the respondents (72.6%) had personal experience with minimally invasive simultaneous resections, and an expanding role for this procedure was foreseen (92.6%), while more evidence was desired (89.6%). Respondents were more reluctant to combine a hepatectomy with low anterior (76.3%) and abdominoperineal resections (73.3%), compared to right (94.4%) and left hemicolectomies (90.7%). Colorectal surgeons were less inclined to combine right or left hemicolectomies with a major hepatectomy than HPB and general surgeons (right: 22.8% vs. 50% and 44.2%, p = 0.008; left: 14% vs. 34% and 35.4%, p = 0.002, respectively). CONCLUSION: The clinical practices and viewpoints on the management of sCRLM differ between continents, and between and within surgical specialties. However, there appears to be consensus on a growing role for MIS and a need for evidence-based input

Microvascular Invasion Does Not Predict Long-Term Survival in Hepatocellular Carcinoma up to 2 cm: Reappraisal of the Staging System for Solitary Tumors

Background: Excellent long-term outcomes have been reported recently for patients with small (≤2 cm) hepatocellular carcinoma (HCC). However, the significance of microvascular invasion (MVI) in small HCC remains unclear. The purpose of this study was to determine the impact of MVI in small HCC up to 2 cm. Methods: In 1,109 patients with solitary HCC from six major international hepatobiliary centers, the impact of MVI on long-term survival in patients with small HCC (≤2 cm) and patients with tumors larger than 2 cm was analyzed. Results: In patients with small HCC, long-term survival was not affected by MVI (p = 0.8), whereas in patients with larger HCC, significantly worse survival was observed in patients with MVI (p 2 cm without MVI, and HCC >2 cm with MVI—significant between-group survival difference was observed (p < 0.0001). Conclusions: Small HCC is associated with an excellent prognosis that is not affected by the presence of MVI. The discriminatory power of the 7th edition of the AJCC classification for solitary HCC could be further improved by subdividing tumors according to size (≤2 vs. >2 cm)

Outcomes comparison of Pancreato-Gastrostomy and Isolated Jejunal Loop Pancreato-Jejunostomy following Pancreato-Duodenectomy in patients with soft pancreas and at moderate-high risk for POPF: a retrospective multicenter experience-based analysis

Following pancreatoduodenectomy (PD), the modality of pancreato-enteric continuity restoration may impact on postoperative pancreatic fistula (POPF) risk. The aim of this study is to compare, among patients with soft pancreas and at moderate/high risk for POPF, the outcomes of PD with Pancreato-Gastrostomy (PG), versus Isolated Jejunal Loop Pancreato-Jejunostomy (IJL-PJ). 193 patients with a Callery Fistula Risk Score (C-FRS) &gt;= 3 operated at 3 HPB Units, two performing PG and one IJL-PJ as their preferred anastomotic technique following PD (2009-2019) were included in this study (PG = 123, IJL-PJ = 70). Primary outcomes were POPF, clinically relevant (cr-)postoperative pancreatic hemorrhage (cr-PPH), delayed gastric emptying (cr-DGE), and postoperative major complications and mortality. POPF, cr-PPH, and cr-DGE occurred in 21.8%, 17.6%, and 11.4% of patients, and did not differ significantly between PG (26%, 19.5%, and 10.6%, respectively) and IJL-PJ (17.1%, 14.3%, and 12.9%, respectively; all p &gt; 0.05) patients. Major (Dindo &gt;= 3) complication and mortality rates were 26.4% and 3.3%, respectively, and did not differ significantly between PG (29.3% and 3.8%) and IJL-PJ (21.4% and 2.9) patients (p &gt; 0.05). A faster surgical drain and nasogastric tube removal matched a significantly shorter hospitalization among IJL-PJ patients (median LOS: 18 days versus 25 days among PG patients, p &lt; 0.001). In conclusion, IJL-PJ and PG, when performed by surgeons specialized with the concerned anastomotic technique in patients with soft pancreas and moderate/high risk for POPF, have similar results in terms of perioperative mortality and postoperative complications both overall and specific for PD

Management of portal annular pancreas during laparoscopic pancreaticoduodenectomy

Portal annular pancreas (PAP) is a pancreatic congenital anomaly consisting of pancreatic parenchyma encircling the portal vein and/or the superior mesenteric vein. It has been reported that the risk of developing a post-operative pancreatic fistula is higher following pancreaticoduodenectomy in patients with PAP, probably because of the possibility of leaving undrained a portion of pancreatic parenchyma during the reconstructive phase. Few manuscripts have reported a surgical technique of pancreaticoduodenectomy in case of PAP, herein we report the first case of a patient with PAP undergoing laparoscopic pancreaticoduodenectomy

Recent Advances in Chemotherapy and Surgery for Colorectal Liver Metastases

BACKGROUND: The liver is the most common site of metastases for colorectal cancer, and combined resection with systemic chemotherapy is the most effective strategy for survival. The aim of this article is to provide a comprehensive summary on four hot topics related to chemotherapy and surgery for colorectal liver metastases (CLM), namely: (1) chemotherapy-related liver injuries: prediction and impact, (2) surgery for initially unresectable CLM, (3) the emerging role of RAS mutations, and (4) the role of hepatic arterial infusion of chemotherapy (HAIC). SUMMARY AND KEY MESSAGES: (1) The use of chemotherapy before liver resection for CLM leads to drug-specific hepatic toxicity, which negatively impacts posthepatectomy outcomes. (2) Curative liver resection of initially unresectable CLM following conversion chemotherapy should be attempted whenever possible, provided that a safe future liver remnant volume is achieved. (3) For CLM, RAS mutation status is needed to guide the use of targeted chemotherapy with anti-epithelial growth factor receptor (EGFR) agents, and is a major prognostic factor that may contribute to optimize surgical strategy. (4) HAIC agents increase the rate of objective response and the rate of complete pathological response