Undifferentiated Embryonal Sarcoma of the Liver (UESL) in Adolescents: An Unexpected Diagnosis.

Definitive diagnosis of pediatric liver masses can be challenging, because clinical manifestations are nonspecific, and ultimate diagnosis may be delayed. We describe 2 patients with liver masses that initially were misdiagnosed and treated as infectious hepatic lesions. Only after histologic examination the correct diagnosis of undifferentiated embryonal sarcoma of the liver was defined. Both patients underwent a complete tumor resection followed by chemotherapy with a favorable outcome.

Treatment of oligo-metastatic pancreatic ductal adenocarcinoma to the liver: is there a role for surgery? A narrative review.

Pancreatic ductal adenocarcinoma (PDAC) is a prognostically unfavorable malignancy that presents with distant metastases at the time of diagnosis in half of patients. Even if patients with metastatic PDAC have not been traditionally considered candidates for surgery, an increasing number of researchers have been investigating the efficacy of surgical treatment for patients with liver-only oligometastases from PDAC, showing promising results in extremely selected patients, mainly with metachronous metastases after perioperative chemotherapy. Nevertheless, a standardized definition of oligometastatic disease should be adopted and additional investigations focusing on the role of perioperative chemotherapy and tumor biology are warranted to reliably assess the role of resection for PDAC metastatic to the liver.

Protective Effect of Minimally Invasive Approach on Postoperative Peak Transaminase Following Liver Resection: A Single-Center Propensity Score-Based Analysis.

BACKGROUND: Postoperative serum ALT levels are one of the most frequently used marker to detect liver tissue damage following liver resection. The aim of this study was to evaluate if minimally invasive liver surgery (MILS) may result in less hepatic injury than open hepatectomy by assessing the differences of postoperative ALT levels. METHODS: Patients who underwent MILS between 2009 and 2019 at our unit were included and compared with open liver resections. Median ALT levels was measured on postoperative day (POD) 1, 3 and 5. Postoperative peak transaminase (PPT) of ALT was determined on POD 1. The stabilized inverse probability treatment weighing (SIPTW) process was used to balance the two groups. A multivariable logistic regression analysis was used to analyze factors associated with high PPT. RESULTS: After SIPTW, 292 MILS were compared with 159 open resections. Median ALT levels on POD 1, 3 and 5 were significantly higher in the open group than in the MILS group (301 vs. 187, p = 0.002; 180 vs. 121, p < 0.0001; 104 vs. 60, p < 0.0001; respectively). At the multivariable logistic regression analysis, MILS showed a protective effect for high PPT. CONCLUSIONS: MILS was associated with significantly lower postoperative ALT levels compared with open liver resections. MILS showed a protective effect for high PPT.

Long-term outcome after laparoscopic fenestration of simple liver cysts.

BACKGROUND: Simple liver cysts (LCs) represent the most common benign liver disease, with a prevalence of 3-5%. Laparoscopic fenestration is considered the best treatment for symptomatic LCs, but few studies have analyzed the rate or type of recurrence during a long-term follow-up period (>5 years). METHODS: Between January 2000 and December 2010, 47 patients underwent laparoscopic fenestration for simple LCs. The indications were symptoms for 42 patients and an uncertain diagnosis for five patients. The follow-up assessment consisted of regular patient evaluations, with results of laboratory data and liver ultrasound. RESULTS: Conversion to laparotomy was not necessary in any case. The postoperative mortality and morbidity rates were nil. The mean follow-up period was 67 months (range 12-142 months), and 26 patients (55.3%) had a follow-up period longer than 5 years. During the follow-up period, 40 patients (85.1%) did not present with any type of recurrence. The overall recurrence rate was 14.9% (seven patients) based on five patients (10.6%) with radiologic asymptomatic recurrences detected by ultrasound or computed tomography (CT) scan and two patients (4.3%) with clinicoradiologic symptomatic recurrences. Both symptomatic recurrences involved LCs located in the right posterior segments. CONCLUSIONS: Laparoscopic fenestration provided complete relief of symptoms for about 95% of patients with simple LCs. Recurrence after surgery was experienced by 14.9% of the patients, but only in 4.3% (two patients) was this recurrence symptomatic requiring a second treatment. The site of recurrence was more frequently in the right posterior segments. Laparoscopic fenestration of symptomatic LCs can be considered a safe and effective procedure that can yield good long-term results.

Intraoperative liver ultrasound still affects surgical strategy for patients with colorectal metastases in the modern era.

BACKGROUND: The present study was designed to evaluate the role of intraoperative ultrasound (IOUS) in intrahepatic staging and the impact on surgical strategy for patients with colorectal liver metastases (CRLM). METHODS: The study included 515 patients who had undergone liver resection for CRLM at two tertiary care referral centers. Data from a prospectively collected database were retrospectively analysed. Early intrahepatic recurrence was assessed at 3 and 6 months after resection and was considered as residual disease undetected by IOUS. Performance of imaging modalities was compared by analysis of studies on individual patients. RESULTS: A total of 1,370 liver metastases were detected preoperatively with a median of 3 imaging modalities. MRI and PET were performed in 51 and 42 % of the patients, respectively. Median number of days between last imaging and surgery was 18. Contrast-enhanced IOUS was performed in 136 patients (26.4 %). Intraoperatively, 293 new nodules were found in 132 patients: on histology 280 were CRLM (17.6 %). Surgical strategy was changed in 140 patients (27.2 %). On multivariate analysis synchronous and bilobar metastases ≥ 3 in number, BMI ≥ 30, and time between last imaging and surgery longer than 18 days resulted in predictive factors indicating new nodules detected by IOUS. Early intrahepatic recurrences were 3.7 and 7.9 % at 3 and 6 months. Performance of CT, MRI, FDG-PET, and intraoperative staging was compared: sensitivity was 63.6, 68.8, 53.6, and 92 % and specificity was 91, 92.3, 95.8, and 97.8 %, respectively CONCLUSIONS: The use of IOUS continues to be mandatory for correct staging of patients with CRLM undergoing liver resection.

Hepatic veins in presurgical planning of hepatic resection: what a radiologist should know.

Hepatic resection is considered to be feasible when all malignant nodules can be technically excised. The goal of the surgical approach is to optimize the oncologic resection (negative margins), sparing the non-cancerous hepatic parenchyma. The outflowing hepatic vein (HV) of that particular liver remnant must be intact in order to preserve its function. The purpose of this article is to familiarize radiologists with anatomy and anatomical variants of HVs, with special emphasis on segmental venous drainage for presurgical planning of hepatic resections. We focus on information which radiologist should give to hepatic surgeon to choose proper surgical approach. Radiologist's familiarity with the anatomy and anatomical variants of HVs is essential for accurate surgical planning to avoid venous congestion as postoperative complication. Any clinically important hepatic vein variation detected on presurgical imaging should be carefully recorded in the radiology report.

Liver resection for gastric cancer metastases.

BACKGROUND/AIMS: Surgical indications in patients with liver metastases from gastric cancer are debated. To analyze outcomes of surgery and the impact of neoadjuvant chemotherapy (NeoCTx). METHODOLOGY: Consecutive patients undergoing liver resection for gastric metastases between January 1997 and December 2008 were analyzed. RESULTS: Liver metastases were synchronous in 9 patients and multiple in 5. Eight patients received NeoCTx. NeoCTx and non-NeoCTx groups had similar characteristics. Mortality was nil, morbidity was 40%. After a mean follow-up of 42.5 months, 5-year survival rate was 33.2%. Presence of multiple metastases was a negative prognostic factor (p=0.029), while synchronous presentation and NeoCTx were not. Disease-free survival rates were significantly different by stratifying patients according to response to chemotherapy: at 5 years 32.4% in non-NeoCTx group, 0% in disease progression (PD) while on NeoCTx group and 60.0% in non-PD while on NeoCTx group (p=0.018). One-year recurrence rates were 40%, 100% and 0%, (p=0.020). CONCLUSIONS: Liver resection for gastric metastases achieves good long-term results, especially in solitary metastases. NeoCTx helps to select candidates for surgery and, in patients without PD, is associated with improved disease-free survival

Bile duct injury after cholecystectomy: timing of surgical repair should be based on clinical presentation. The experience of a tertiary referral center with Hepp-Couinaud hepatico-jejunostomy.

Impact of timing of repair on outcomes of patients repaired with Hepp-Couinaud hepatico-jejunostomy (HC-HJ) after bile duct injury (BDI) during cholecystectomy remains debated. This is an observational retrospective study at a tertiary referral hepato-biliary center. HC-HJ was always performed in patients without sepsis or bile leak and with dilated bile ducts. Timing of repair was classified as: early (≤ 2 weeks), intermediate (> 2 weeks, ≤ 6 weeks), and delayed (> 6 weeks). 114 patients underwent HC-HJ between 1994 and 2022: 42.1% underwent previous attempts of repair at referring institutions (Group A) and 57.9% were referred without any attempt of repair before referral (Group B). Overall, a delayed HC-HJ was performed in 78% of patients; intermediate and early repair were performed in 17% and 6%, respectively. In Group B, 10.6% of patients underwent an early, 27.3% an intermediate, and 62.1% a delayed repair. Postoperative mortality was nil. Median follow-up was 106.7 months. Overall primary patency (PP) attainment rate was 94.7%, with a 5- and 10-year actuarial primary patency (APP) of 84.6% and 84%, respectively. Post-repair bile leak was associated with PP loss in the entire population (odds ratio [OR] 9.75, 95% confidence interval [CI] 1.64-57.87, p = 0.012); no correlation of PP loss with timing of repair was noted. Treatment of anastomotic stricture (occurred in 15.3% of patients) was performed with percutaneous treatment, achieving absence of biliary symptoms in 93% and 91% of cases at 5 and 10 years, respectively. BDI can be successfully repaired by HC-HJ regardless of timing when surgery is performed in stable patients with dilated bile ducts and without bile leak.

The Impact of KRAS Mutational Status on Long-Term Survival following Liver Resection for Hilar Cholangiocarcinoma.

KRAS mutation is reportedly associated with poor prognosis in patients with different cancer types. However, mutational data on hilar cholangiocarcinoma are few and controversial. The aim of this study was to evaluate the rate of KRAS mutations in a single-center homogeneous population resected for hilar cholangiocarcinoma and the subsequent impact on prognosis. KRAS mutation status was evaluated in 54 patients undergoing major hepatectomy combined with resection of the main biliary confluence and regional lymphadenectomy for hilar cholangiocarcinoma between 2001 and 2019. Among these 54 patients, 12 (22.2%) had a KRAS mutation. KRAS mutation was not related with pathologic characteristics of the tumor. Five-year overall survival (OS) in patients with KRAS mutation was significantly lower than that observed in patients with KRAS wild type (0 vs. 49.2%, respectively; p = 0.003). In the multivariable analysis; independent predictors of poor OS were KRAS mutation (HR = 5.384; p = 0.003) and lymph node metastases (HR = 2.805; p = 0.023). The results of our study suggested that KRAS mutation in hilar cholangiocarcinoma was not rarely observed. KRAS mutation was an independent strong predictor of poor OS. KRAS mutation analysis should be included in the routine pathologic evaluation of resected hilar cholangiocarcinoma in order to better stratify prognosis.

High Arterial Lactate Levels after Hepatic Resection Are Associated with Low Oxygen Delivery and Predict Severe Postoperative Complications.

High End-Surgery Arterial Lactate Concentration (ES-ALC) predicts poor outcome after hepatectomy. The aim of this study was to identify intraoperative hemodynamic parameters predicting high ES-ALC during elective liver resection. Patients who underwent liver resection between 2017 and 2018, under FloTrac/EV1000TM hemodynamic monitoring, were included. The ES-ALC cutoff best predicting severe postoperative complications was identified. Association between high ES-ALC and preoperative and intraoperative variables was assessed. 108 patients were included; 90-day mortality was 0.9% and severe morbidity 14.8%. ES-ALC cutoff best discriminating severe complications was 5.05 mmol/L. Patients with ES-ALC > 5.0 mmol/L had a relative risk of severe complications of 2.8% (p = 0.004). High ES-ALC patients had longer surgery and ischemia duration, larger blood losses and higher requirements of fluids and blood transfusions. During surgery, hemoglobin concentration and oxygen delivery (DO2) decreased more significantly in patients with high ES-ALC, although they had similar values of stroke volume and cardiac output to those of other patients. At multivariate analysis, surgery duration and lowest recorded DO2 value were the strongest predictors of high ES-ALC. ES-ALC > 5.0 mmol/L in elective liver resection predicts postoperative morbidity and is essentially driven by the impaired DO2. Timely correction of blood losses might prevent the ES-ALC increase.

Survival by Number and Sites of Resections of Recurrence after First Curative Resection of Colorectal Liver Metastases.

BACKGROUND: Recurrence after curative hepatectomy for colorectal liver metastases (CRLM) is common. We sought to determine if number and sites of resections of recurrence after hepatectomy for CRLM impact survival. METHODS: The study included patients who underwent resection of recurrence following complete curative-intent resection of CRLM during 1998-2016 at two academic medical centers in Houston, USA, and Rome, Italy. The survival impacts of number and sites of resections of recurrence were evaluated. Patients with synchronous extrahepatic disease at curative CRLM resection were excluded. RESULTS: Among 2163 patients who underwent curative hepatectomy, 1456 (67.3%) developed a recurrence. Four hundred seventy-eight patients underwent one (322/478; 67.4%) or two or more (156/478; 32.6%) resections of recurrence. The 5-year overall survival (OS) rate was higher in patients with resected than unresected recurrence (70.2% vs. 24.0%; p < 0.001). In patients who underwent only one resection of recurrence, the 5-year OS rate differed by location (lung, 81.6%; liver, 64.3%; other, 54.1%). In patients who underwent two or more resections of recurrence, the 5-year OS rate was similar for liver-only resection (87.5%) and resection of liver and other sites (66.1%) (p = 0.223) and for liver-only resection and other-sites-only resection (80.7%) (p = 0.258); 5-year OS rate by site of first resection of recurrence did not differ between liver (78.5%) and lung (81.8%) (p = 0.502) but was worse for other sites (61.1%) than for lung (p = 0.045). CONCLUSION: When recurrence after initial CRLM resection is resectable, the ability to undergo resection was associated with improved survival and can be considered as an option regardless of the number of recurrence and resection. Sites of resection of recurrence impact survival and should be considered.

Discordance of KRAS Mutational Status between Primary Tumors and Liver Metastases in Colorectal Cancer: Impact on Long-Term Survival Following Radical Resection.

If KRAS mutation status of primary colorectal tumor is representative of corresponding colorectal liver metastases (CRLM) mutational pattern, is controversial. Several studies have reported different rates of KRAS discordance, ranging from 4 to 32%. Aim of this study is to assess the incidence of discordance and its impact on overall survival (OS) in a homogenous group of patients. KRAS mutation status was evaluated in 107 patients resected for both primary colorectal tumor and corresponding CRLM at the same institution, between 2007 and 2018. Discordance rate was 15.9%. Its incidence varied according to the time interval between the two mutation analyses (p = 0.025; Pearson correlation = 0.2) and it was significantly higher during the first 6 months from the time of primary tumor evaluation. On multivariable analysis, type of discordance (wild-type in primary tumor, mutation in CRLM) was the strongest predictor of poor OS (p < 0.001). At multivariable logistic regression analysis, the number of CRLM >3 was an independent risk factor for the risk of KRAS discordance associated with the worst prognosis (OR = 4.600; p = 0.047). Results of our study suggested that, in the era of precision medicine, possibility of KRAS discordance should be taken into account within multidisciplinary management of patients with metastatic colorectal cancer.

Liver Metastasectomy for Metastatic Breast Cancer Patients: A Single Institution Retrospective Analysis.

The liver represents the first metastatic site in 5-12% of metastatic breast cancer (MBC) cases. In absence of reliable evidence, liver metastasectomy (LM) could represent a possible therapeutic option for selected MBC patients (patients) in clinical practice. A retrospective analysis including MBC patients who had undergone an LM after a multidisciplinary Tumor Board discussion at the Hepatobiliary Surgery Unit of Fondazione Policlinico Universitario "Agostino Gemelli" IRCCS in Rome, between January 1994 and December 2019 was conducted. The primary endpoint was overall survival (OS) after a MBC-LM; the secondary endpoint was the disease-free interval (DFI) after surgery. Forty-nine MBC patients underwent LM, but clinical data were only available for 22 patients. After a median follow-up of 71 months, median OS and DFI were 67 months (95% CI 45-103) and 15 months (95% CI 11-46), respectively. At univariate analysis, the presence of a negative resection margin (R0) was the only factor that statistically significantly influenced OS (78 months versus 16 months; HR 0.083, p < 0.0001) and DFI (16 months versus 5 months; HR 0.17, p = 0.0058). A LM for MBC might represent a therapeutic option for selected patients. The radical nature of the surgical procedure performed in a high-flow center and after a multidisciplinary discussion appears essential for this therapeutic option.

Does hepatic pedicle clamping affect disease-free survival following liver resection for colorectal metastases?

OBJECTIVE: To evaluate the impact of liver ischemia from hepatic pedicle clamping (HPC) on long-term outcome after hepatectomy for colorectal liver metastases (CRLM). BACKGROUND: Liver resection offers the only chance of cure for patients with CRLM. Several clinical and pathologic factors have been reported as determinants of poor outcome after hepatectomy for CRLM. A controversial issue is that hepatic ischemia/reperfusion injury from HPC may adversely affect long-term outcome by accelerating the outgrowth of residual hepatic micrometastases. METHODS: Patients undergoing liver resection for CRLM in 2 tertiary referral centers, between 1992 and 2008, were included. Disease-free survival and specific liver-free survival were analyzed according to the use, type, and duration of HPC. RESULTS: Five hundred forty-three patients had primary hepatectomy for CRLM. Hepatic pedicle clamping was performed in 355 patients (65.4%), and intermittently applied in 254 patients (71.5%). Postoperative mortality and morbidity rates were 1.3% and 18.5%, respectively. Hepatic pedicle clamping had a highly significant impact in reducing the risk of blood transfusions and was not correlated with significantly higher postoperative morbidity. Liver recurrence rate was not significantly different according to the use, type, and duration of HPC, in patients resected after preoperative chemotherapy as well. On univariate analysis, HPC did not significantly affect overall and disease-free survival. These results were confirmed on the multivariate analysis where blood transfusions, primary tumor nodal involvement, and the size of CRLM of more than 5 cm prevailed as determinants of poor outcome. CONCLUSIONS: This study confirms the safety and effectiveness of HPC and demonstrates that in the human situation, there is no evidence that HPC may adversely affect long-term outcome after hepatectomy for CRLM.

The impact of personalized nutritional support on postoperative outcome within the enhanced recovery after surgery (ERAS) program for liver resections: results from the NutriCatt protocol.

BACKGROUND: Malnutrition in liver surgery is correlated with higher postoperative complications and longer length of hospital stay (LOHS), the same items that ERAS programs try to optimize. However, to date, standardized dietary protocols have not been defined within ERAS programs. Aim of this study was to evaluate the impact on LOHS and postoperative complications, of a personalized nutritional protocol (NutriCatt) with diet and oral branched-chain amino acid (BCAA) supplementation, adopted within the ERAS program. METHODS: 1960 consecutive liver resections were performed from January 2000 to September 2018. EXCLUSION CRITERIA: perihilar cholangiocarcinoma, simultaneous colorectal and liver resections. Four groups for analysis: resections before 2009 (1st period); from 2009 to 2016 (2nd period, including laparoscopic resections); between 2016 and September 2017 (ERAS); after September 2017 (ERAS + NutriCatt). RESULTS: LOHS declined (p < 0.0001), from a median of 10 days (1st period) to 8, 7 and 6 in 2nd period, ERAS and ERAS + NutriCatt groups, respectively. At multivariable analysis for risk of LOHS > 8 days, the 2nd period, ERAS and ERAS + NutriCatt groups showed a protective effect. These results were confirmed for both minor and major resections. LOHS was significantly lower in ERAS + Nutricatt group than in ERAS group, without increasing risk of postoperative complications, although the rate of laparoscopic resections was similar in these two groups and complexity of liver resections was significantly higher in the last period. CONCLUSIONS: Adoption of a personalized nutritional protocol with BCAA supplementation within the ERAS program for liver resections was a safe and effective approach that may impact on reducing the LOHS.

The impact of multidisciplinary team management on outcome of hepatic resection in liver-limited colorectal metastases.

Hepatic resection is the gold standard treatment for patients affected by liver-limited colorectal metastases. Reports addressing the impact of multidisciplinary team (MDT) evaluation on survival are controversial. The aim of this study was to evaluate the benefit of MDT management in these patients in our Institution experience. The objective of the analysis was to compare survivals of patients managed within our MDT (MDT cohort) to those of patients referred to surgery from other hospitals without MDT discussion (non-MDT cohort). Of the 523 patients, 229 were included in the MDT cohort and 294 in the non-MDT cohort. No difference between the two groups was found in terms of median overall survival (52.5 vs 53.6 months; HR 1.13; 95% CI, 0.88-1.45; p = 0.344). In the MDT cohort there was a higher number of metastases (4.5 vs 2.7; p < 0.0001). The median duration of chemotherapy was lower in MDT patients (8 vs 10 cycles; p < 0.001). Post-operative morbidity was lower in the MDT cohort (6.2 vs 21.5%; p < 0.001). One hundred and ninety-seven patients in each group were matched by propensity score and no significant difference was observed between the two groups in terms of OS and DFS. Our study does not demonstrate a survival benefit from MDT management, but it allows surgery to patients with a more advanced disease. MDT assessment reduces the median duration of chemotherapy and post-operative morbidities.

Role of the surgeon as a variable in long-term survival after liver resection for colorectal metastases.

BACKGROUND AND OBJECTIVES: Survival analyses after hepatectomy for colorectal liver metastases (CRLM) mostly address tumor-related factors; this study has simultaneously evaluated interventional factors which may be influenced by the surgeon. METHODS: Operative and long-term results of 251 consecutive patients undergoing hepatectomy for CRLM between 1992 and 2007 were analyzed. RESULTS: Mortality was 0.8%, morbidity 22.9%, intraoperative blood transfusion rate 23.1% (19.4% with pedicle clamping, 35.0% without clamping, P = 0.01), R0-resection 93.6% (2/3 with tumor-free margin >5 mm). The 3-, 5-, 10-year overall and disease-free survival rates were 55.2%, 38.9%, 24.2%, and 37.1%, 28.2%, 25.4%. Univariate analysis: lower survival was related to transfusion requirement, tumor size >5 cm, tumor-free margin < or =5 mm, major hepatectomy, R1-resection, multiplicity of CRLM, preoperative CEA > or =50 ng/ml. Multivariate analysis: intraoperative transfusion remained the only independent predictor of survival; tumor-free margin < or =5 mm and multiplicity of CRLM remained independent predictors of disease-free survival within 12 months from hepatectomy; intraoperative transfusion became again the prominent predictor for later recurrences. CONCLUSIONS: Two factors may be influenced by the surgeon: bleeding with requirement for blood transfusion (through the protective effect of pedicle clamping) and width of tumor-free surgical margin. These factors have prominent roles on long-term outcomes after hepatectomy for CRLM.

Left hepatectomy for metastatic thrombosis of umbilical vein and left portal vein from renal cell carcinoma.

Renal cell carcinoma is an aggressive tumor which is often advanced at the time of diagnosis; its distant spread can take a lymphatic route or, more often, a vascular route (renal vein and inferior vena cava), but tumor thrombosis of left portal vein extending into the round ligament (the umbilical vein) coming from this tumor, to our knowledge, has never been described. We report the case of a metastatic thrombosis of left portal vein and of the umbilical vein from renal cell carcinoma, developed 13 years after nephrectomy, which was successfully treated with left hepatectomy. The experience with hepatectomy for metastatic renal cell carcinoma has been rarely reported. Nevertheless radical hepatectomy is considered to be the only opportunity for curative treatment for selected patients with metastatic renal cell carcinoma.