Factors affecting overall survival and disease-free survival after surgery for hepatocellular carcinoma: a nomogram-based prognostic model-a Western European multicenter study.

Few studies have assessed the clinical implications of the combination of different prognostic indicators for overall survival (OS) and disease-free survival (DFS) of resected hepatocellular carcinoma (HCC). This study aimed to evaluate the prognostic factors in HCC patients for OS and DFS outcomes and establish a nomogram-based prognostic model to predict the DFS of HCC. A multicenter, retrospective European study was conducted through the collection of data on 413 consecutive treated patients with a first diagnosis of HCC between January 2010 and December 2020. Univariate and multivariate Cox regression analyses were performed to identify all independent risk factors for OS and DFS outcomes. A nomogram prognostic staging model was subsequently established for DFS and its precision was verified internally by the concordance index (C-Index) and externally by calibration curves. For OS, multivariate Cox regression analysis indicated Child-Pugh B7 score (HR 4.29; 95% CI 1.74-10.55; p = 0.002) as an independent prognostic factor, along with Barcelona Clinic Liver Cancer (BCLC) stage ≥ B (HR 1.95; 95% CI 1.07-3.54; p = 0.029), microvascular invasion (MVI) (HR 2.54; 95% CI 1.38-4.67; p = 0.003), R1/R2 resection margin (HR 1.57; 95% CI 0.85-2.90; p = 0.015), and Clavien-Dindo Grade 3 or more (HR 2.73; 95% CI 1.44-5.18; p = 0.002). For DFS, multivariate Cox regression analysis indicated BCLC stage ≥ B (HR 2.15; 95% CI 1.34-3.44; p = 0.002) as an independent prognostic factor, along with multiple nodules (HR 2.04; 95% CI 1.25-3.32; p = 0.004), MVI (HR 1.81; 95% CI 1.19-2.75; p = 0.005), satellite nodules (HR 1.63; 95% CI 1.09-2.45; p = 0.018), and R1/R2 resection margin (HR 3.39; 95% CI 2.19-5.25; < 0.001). The C-Index of the nomogram, tailored based on the previous significant factors, showed good accuracy (0.70). Internal and external calibration curves for the probability of DFS rate showed optimal consistency and fit well between the nomogram-based prediction and actual observations. MVI and R1/R2 resection margins should be considered as significant OS and DFS predictors, while satellite nodules should be included as a significant DFS predictor. The nomogram-based prognostic model for DFS provides a more effective prognosis assessment for resected HCC patients, allowing for individualized treatment plans.

Comparison of Surgical Risk Scores in a European Cohort of Patients with Advanced Chronic Liver Disease.

Patients with advanced chronic liver disease (ACLD) or cirrhosis undergoing surgery have an increased risk of morbidity and mortality in contrast to the general population. This is a retrospective, observational study to evaluate the predictive capacity of surgical risk scores in European patients with ACLD. Cirrhosis was defined by the presence of thrombocytopenia with <150,000/uL and splenomegaly, and AST-to-Platelet Ratio Index >2, a nodular liver edge seen via ultrasound, transient elastography of >15 kPa, and/or signs of portal hypertension. We assessed variables related to 90-day mortality and the discrimination and calibration of current surgical scores (Child-Pugh, MELD-Na, MRS, NSQIP, and VOCAL-Penn). Only patients with ACLD and major surgeries included in VOCAL-Penn were considered (n = 512). The mortality rate at 90 days after surgery was 9.8%. Baseline disparities between the H. Mar and VOCAL-Penn cohorts were identified. Etiology, obesity, and platelet count were not associated with mortality. The VOCAL-Penn showed the best discrimination (C-statistic90D = 0.876) and overall predictive capacity (Brier90D = 0.054), but calibration was not excellent in our cohort. VOCAL-Penn was suboptimal in patients with diabetes (C-statistic30D = 0.770), without signs of portal hypertension (C-statistic30D = 0.555), or with abdominal wall (C-statistic30D = 0.608) or urgent (C-statistic180D = 0.692) surgeries. Our European cohort has shown a mortality rate after surgery similar to those described in American studies. However, some variables included in the VOCAL-Penn score were not associated with mortality, and VOCAL-Penn's discriminative ability decreases in patients with diabetes, without signs of portal hypertension, and with abdominal wall or urgent surgeries. These results should be validated in larger multicenter and prospective studies.

Clinical Guideline on Perioperative Management of Patients with Advanced Chronic Liver Disease.

(1) Background: Patients with advanced chronic liver disease (ACLD) are living longer with more comorbidities because of improved medical and surgical management. However, patients with ACLD are at increased risk of perioperative morbidity and mortality; (2) Methods: We conducted a comprehensive review of the literature to support a narrative clinical guideline about the assessment of mortality risk and management of perioperative morbidity in patients with ACLD undergoing surgical procedures; (3) Results: Slight data exist to guide the perioperative management of patients with ACLD, and most recommendations are based on case series and expert opinion. The severity of liver dysfunction, portal hypertension, cardiopulmonary and renal comorbidities, and complexity of surgery and type (elective versus emergent) are predictors of perioperative morbidity and mortality. Expert multidisciplinary teams are necessary to evaluate and manage ACLD before, during, and after surgical procedures; (4) Conclusions: This clinical practice document updates the available data and recommendations to optimize the management of patients with advanced chronic liver disease who undergo surgical procedures.

Use of failure-to-rescue after emergency surgery as a dynamic indicator of hospital resilience during the COVID-19 pandemic. A multicenter retrospective propensity score-matched cohort study.

BACKGROUND: Surgical failure-to-rescue (FTR, death rate following complications) is a reliable cross-sectional quality of care marker, but has not been evaluated dynamically. We aimed to study changes in FTR following emergency surgery during the COVID-19 pandemic. MATERIAL AND METHODS: Matched cohort study including all COVID-19-non-infected adult patients undergoing emergency general surgery in 25 Spanish hospitals during COVID-19 pandemic peak (March-April 2020), non-peak (May-June 2020), and 2019 control periods. A propensity score-matched comparative analysis was conducted using a logistic regression model, in which period was regressed on observed baseline characteristics. Subsequently, a mixed effects logistic regression model was constructed for each variable of interest. Main variable was FTR. Secondary variables were post-operative complications, readmissions, reinterventions, and length of stay. RESULTS: 5003 patients were included (948, 1108, and 2947 in the pandemic peak, non-peak, and control periods), with comparable clinical characteristics, prognostic scores, complications, reintervention, rehospitalization rates, and length of stay across periods. FTR was greater during the pandemic peak than during non-peak and pre-pandemic periods (22.5% vs. 17.2% and 12.7%), being this difference confirmed in adjusted analysis (odds ratio [OR] 2.13, 95% confidence interval [95% CI] 1.27-3.66). There was sensible inter-hospital variability in FTR changes during the pandemic peak (median FTR change +8.77%, IQR 0-29.17%) not observed during the pandemic non-peak period (median FTR change 0%, IQR -6.01-6.72%). Greater FTR increase was associated with higher COVID-19 incidence (OR 2.31, 95% CI 1.31-4.16) and some hospital characteristics, including tertiary level (OR 3.07, 95% CI 1.27-8.00), medium-volume (OR 2.79, 95% CI 1.14-7.34), and high basal-adjusted complication risk (OR 2.21, 95% CI 1.07-4.72). CONCLUSION: FTR following emergency surgery experienced a heterogeneous increase during different periods of the COVID-19 pandemic, suggesting it to behave as an indicator of hospital resilience. FTR monitoring could facilitate identification of centres in special needs during ongoing health care challenges.

P-POSSUM as mortality predictor in COVID-19-infected patients submitted to emergency digestive surgery. A retrospective cohort study.

BACKGROUND: COVID-19 infection is associated with a higher mortality rate in surgical patients, but surgical risk scores have not been validated in the emergency setting. We aimed to study the capacity for postoperative mortality prediction of the P-POSSUM score in COVID-19-positive patients submitted to emergency general and digestive surgery. MATERIAL AND METHODS: Consecutive patients undergoing emergency general and digestive surgery from March to June 2020, and from March to June 2019 in 25 Spanish hospitals were included in a retrospective cohort study. MAIN OUTCOME: 30-day mortality. P-POSSUM discrimination was quantified by the area under the curve (AUC) of ROC curves; calibration was assessed by linear regression slope (ß estimator); and sensitivity and specificity were expressed as percentage and 95% confidence interval (CI). RESULTS: 4988 patients were included: 177 COVID-19-positive; 2011 intra-pandemic COVID-19-negative; and 2800 pre-pandemic. COVID-19-positive patients were older, with higher surgical risk, more advanced pathologies, and higher P-POSSUM values (1.79% vs. 1.09%, p < 0.001, in both the COVID-19-negative and control cohort). 30-day mortality in the COVID-19-positive, intra-pandemic COVID-19-negative and pre-pandemic cohorts were: 12.9%, 4.6%, and 3.2%. The P-POSSUM predictive values in the three cohorts were, respectively: AUC 0.88 (95% CI 0.81-0.95), 0.89 (95% CI 0.87-0.92), and 0.91 (95% CI 0.88-0.93); ß value 0.97 (95% CI 0.74-1.2), 0.99 (95% CI 0.82-1.16), and 0.78 (95% CI 0.74-0.82); sensitivity 83% (95% CI 61-95), 91% (95% CI 84-96), and 89% (95% CI 80-94); and specificity 81% (95% CI 74-87), 76% (95% CI 74-78), and 80% (95% CI 79-82). CONCLUSION: The P-POSSUM score showed a good predictive capacity for postoperative mortality in COVID-19-positive patients submitted to emergency general and digestive surgery.

Changes of liver hemodynamic and elastography parameters in patients with colorectal liver metastases receiving preoperative chemotherapy: "a note of caution".

BACKGROUND: New systemic chemotherapy agents have improved prognosis in patients with colorectal liver metastases (CLM), but some of them damage the liver parenchyma and ultimately increase postoperative morbidity and mortality after liver resection. The aims of our study were to determine the degree of hemodynamic and pathological liver injury in CLM patients receiving preoperative chemotherapy and to identify an association between these injuries and postoperative complications after liver resection. METHODS: This is a prospective descriptive study of patients with CLM receiving preoperative chemotherapy before curative liver resection from November 2013 to June 2014. All patients had preoperative elastography and hepatic hemodynamic evaluation. We analyzed clinical preoperative data and postoperative outcomes after grouping the patients by chemotherapy type, development of sinusoidal obstructive syndrome (SOS), and development of major complications. RESULTS: Eleven from the 20 patients included in the study received preoperative oxaliplatin-based chemotherapy (OBC). Nine patients had SOS at pathological analysis and five patients developed major complications. Patients receiving preoperative OBC had higher values of hepatic venous pressure gradient (HVPG) and developed more SOS and major complications. Patients developing SOS had higher values of HVPG and developed more major complications. Patients with major complications had higher values of HVPG, and patients with a HVPG of 5 mmHg or greater had more major complications than those under 5 mmHg (20 vs 80%, p = 0.005). CONCLUSIONS: OBC and SOS impair liver hemodynamics in CLM patients. An increase in major complications after liver resection in these patients develops at subclinical HVPG levels.

Letter in reply: Prognostic prediction by liver tissue proteomic profiling in patients with colorectal liver metastases.

In response to: S Sabour. Prognostic prediction by liver tissue proteomic profiling in patients with colorectal liver metastases; rule of thumb.

Prognostic prediction by liver tissue proteomic profiling in patients with colorectal liver metastases.

AIM: To obtain proteomic profiles in patients with colorectal liver metastases (CRLM) and identify the relationship between profiles and the prognosis of CRLM patients. MATERIALS & METHODS: Prognosis prediction (favorable or unfavorable according to Fong's score) by a classification and regression tree algorithm of surface-enhanced laser desorption/ionization TOF-MS proteomic profiles from cryopreserved CRLM (patients) and normal liver tissue (controls). RESULTS: The protein peak 7371 m/z showed the clearest differences between CRLM and control groups (94.1% sensitivity, 100% specificity, p < 0.001). The algorithm that best differentiated favorable and unfavorable groups combined 2970 and 2871 m/z protein peaks (100% sensitivity, 90% specificity). CONCLUSION: Proteomic profiling in liver samples using classification and regression tree algorithms is a promising technique to differentiate healthy subjects from CRLM patients and to classify the severity of CRLM patients.

Laparoscopic Distal Pancreatectomy for Pancreatic Tumors: Does Size Matter?

BACKGROUND: Laparoscopic distal pancreatectomy (LDP) for large pancreatic tumors may require prolonged dissection, and this could be associated with increased operative time and intraoperative complications. METHODS: From a total cohort of 190 consecutive patients undergoing LDP, 18 patients were found to have pancreatic tumors >5 cm and were included in the retrospective study of prospectively collected data. Three techniques were used to approach the splenic vessels: the superior pancreatic, the inferior supracolic and post-pancreatic transection. RESULTS: Of these 18 patients, 13 were women and 5 were men, the median age was 68 years and their median tumor size 7 cm. Exocrine pancreatic malignancy was diagnosed in 8 patients, 6 patients had neuroendocrine pancreatic tumors and 4 patients cystic neoplasm. The median number of resected nodes was 14. R1 resections for exocrine pancreatic malignancies were found in 50% of patients. Morbidity (grade >II) was found in 16.6% of patients and 30 days mortality in 1 patient. Overall median survival was 50 months and 29 months for patients with exocrine pancreatic malignancies. CONCLUSIONS: LDP for large tumors, while technically demanding, is possible without additional morbidity and did not compromise short- and long-term oncological outcomes.

Trombocitopenia severa después de una pancreatectomía distal con preservación esplénica y resección de los vasos esplénicos por laparoscopia / Severe thrombocytopenia after laparoscopic distal pancreatectomy with splenic preservation and resection of splenic vessels

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Cirugía del gastrinoma: Resultados inmediatos y a largo plazo / Surgery for gastrinoma: Short and long-term results

INTRODUCCIÓN: El síndrome de Zollinger-Ellison (Z-E) está caracterizado por tumores productores de gastrina responsables de la aparición de úlceras recurrentes en el tracto gastrointestinal. El abordaje quirúrgico y la extensión de la resección tumoral son todavía controvertidos. MÉTODOS: De febrero de 2005 a febrero de 2014 se intervino a 6 pacientes con Z-E, 4 hombres y 2 mujeres, con una mediana de edad 46,8 años (22-61). Dos pacientes presentaban una neoplasia endocrina múltiple-1 (NEM-1). El diagnóstico se estableció por la determinación de gastrina basal en ayunas >200 pg/ml (VN < 100). Para el diagnóstico de localización se utilizó el octreoscan (6/6), la tomografía axial computarizada (TAC) (6/6) y la ultrasonografía endoscópica (USE) (1/6). RESULTADOS: El octreoscan fue positivo en 5 pacientes. La TAC localizó el tumor en todos los pacientes: páncreas (2), duodeno (3, uno confirmado por USE), entre el conducto biliar y la vena cava (uno). El abordaje laparoscópico se utilizó en 4 pacientes, 2 pacientes fueron convertidos a cirugía abierta. Entre las técnicas quirúrgicas se realizaron: 2 duodenopancreatectomías cefálicas con preservación pilórica (DPCPP), una pancreatectomía distal con preservación esplénica, una resección nodular duodenal, una resección duodenal segmentaria y una resección nodular extrapancreática. La anatomía patológica demostró metástasis linfáticas en 2 pacientes con gastrinomas pancreáticos y en un paciente con gastrinoma duodenal. La estancia hospitalaria mediana fue 11,3 días (10-14). Durante el período de seguimiento clínico, con una mediana de 76,83 meses (5-108), todos los pacientes presentaron una gastrina en ayunas normal CONCLUSIONES: La cirugía puede ofrecer la curación en pacientes con Z-E. El abordaje laparoscópico permanece limitado a casos seleccionados

INTRODUCTION: Zollinger-Ellison syndrome (Z-E) is characterized by gastrin-secreting tumors, responsible for causing refractory and recurrent peptic ulcers in the gastrointestinal tract. The optimal approach and the extension of tumor resection remains the subject of debate. METHODS: During the period February 2005 and February 2014, 6 patients with Z-E underwent surgery, 4 men and 2 women with a median age 46.8 years (22-61). Two patients were affected with multiple endocrine neoplasia type-1 (MEN-1). Fasting gastrin levels greater than 200 pg/ml (NV: <100) was diagnostic. Radiologic imaging to localize the lesion included octreoscan 6/6, computer tomography (CT) 6/6, and endoscopic ultrasonography (EUS) 1/6. RESULTS: The octreoscan was positive in 5 patients. The CT localized the tumor in the pancreas in 2 patients, in the duodenum in 3 patients (1 confirmed by EUS) and between the common bile duct and vena cava in one patient. The laparoscopic approach was used in 4 patients, 2 patients converted to open surgery. The following surgical techniques were performed: 2 pylorus-preserving pancreatico-duodenectomy (PPPD), one spleen-preserving distal pancreatectomy, one duodenal nodular resection, 1 segmental duodenectomy and one extrapancreatic nodular resection. Pathological studies showed lymph nodes metástasis in 2 patients with pancreatic gastrinomas, and in one patient with duodenal gastrinoma. The median follow-up was 76,83 months (5-108) and all patients presented normal fasting gastrin levels. CONCLUSIONS: Surgery may offer a cure in patients with Z-E. The laparoscopic approach remains limited to selected cases

[Surgery for gastrinoma: Short and long-term results]. / Cirugía del gastrinoma: Resultados inmediatos y a largo plazo.

INTRODUCTION: Zollinger-Ellison syndrome (Z-E) is characterized by gastrin-secreting tumors, responsible for causing refractory and recurrent peptic ulcers in the gastrointestinal tract. The optimal approach and the extension of tumor resection remains the subject of debate. METHODS: During the period February 2005 and February 2014, 6 patients with Z-E underwent surgery, 4 men and 2 women with a median age 46.8 years (22-61). Two patients were affected with multiple endocrine neoplasia type-1 (MEN-1). Fasting gastrin levels greater than 200pg/ml (NV: <100) was diagnostic. Radiologic imaging to localize the lesion included octreoscan 6/6, computer tomography (CT) 6/6, and endoscopic ultrasonography (EUS) 1/6. RESULTS: The octreoscan was positive in 5 patients. The CT localized the tumor in the pancreas in 2 patients, in the duodenum in 3 patients (1 confirmed by EUS) and between the common bile duct and vena cava in one patient. The laparoscopic approach was used in 4 patients, 2 patients converted to open surgery. The following surgical techniques were performed: 2 pylorus-preserving pancreatico-duodenectomy (PPPD), one spleen-preserving distal pancreatectomy, one duodenal nodular resection, 1 segmental duodenectomy and one extrapancreatic nodular resection. Pathological studies showed lymph nodes metástasis in 2 patients with pancreatic gastrinomas, and in one patient with duodenal gastrinoma. The median follow-up was 76,83 months (5-108) and all patients presented normal fasting gastrin levels. CONCLUSIONS: Surgery may offer a cure in patients with Z-E. The laparoscopic approach remains limited to selected cases.

Prognostic value of serum neutrophil gelatinase-associated lipocalin in metastatic and nonmetastatic colorectal cancer.

BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) expression is increased in epithelial cancer patients, but studies showing its relation to prognosis are scarce. We aimed to test the ability of preoperative serum NGAL levels (pNGAL) to predict recurrence in metastatic and nonmetastatic colorectal cancer (CRC) patients. METHODS: This retrospective study determined pNGAL levels in 60 healthy individuals, 47 patients with nonmetastatic CRC, and 70 patients with metastatic CRC undergoing curative neoplastic resection. Patients were divided into low- and high-pNGAL groups using a median series-based cutoff. RESULTS: The mean ± SD pNGAL in CRC patients (nonmetastatic and metastatic) was 102.3 ± 66.6 (median 91.4). Nonmetastatic CRC and metastatic CRC patients had higher pNGAL than healthy controls (88 ± 64 and 112 ± 67 vs. 0.6 ± 0.3, respectively, both p < 0.0001). Nonmetastatic CRC patients with deeper tumor invasion and metastatic CRC patients with shorter disease-free interval after CRC resection had higher pNGAL. pNGAL levels correlated with neoplastic tissue volume. CRC patients with recurrence had higher pNGAL than those without recurrence (118 ± 64 vs. 88 ± 66, p = 0.013), and high-pNGAL patients had a higher recurrence rate (59.3 vs. 36.2 %, p = 0.016). Median pNGAL-based risk classification had a sensitivity of 62.5 % for predicting neoplastic progression in CRC patients and 74.3 % for predicting neoplastic progression during the first year after metastatic CRC resection. CONCLUSIONS: pNGAL is higher in CRC patients than in the healthy population, which indicates a potential screening role. High-pNGAL levels are associated with higher neoplastic tissue volume, characteristics of neoplastic invasion, and recurrence, showing a prognostic utility mainly in metastatic CRC patients.

Effects of graft quality on non-urgent liver retransplantation survival: should we avoid high-risk donors?

BACKGROUND: Few studies have studied the effects of graft quality on non-urgent liver retransplantation (ReLT) outcomes. We aimed to analyze graft characteristics and survival in non-urgent ReLT and the effect of using grafts with extended criteria on survival. METHODS: Eighty non-urgent ReLT were performed from June 1988 to June 2010. The whole series was divided by identical time periods to study time-related effects. We assessed graft quality with donor risk index (DRI) and Briceño scores and recipient status with the Model for End-stage Liver Diseases and Rosen scores. Low and high-risk grafts were defined by a DRI cutoff of 1.8. RESULTS: Graft survival was similar in both periods (1-, 5-, and 10-year graft survivals: 73.5, 46.9, and 40.8 versus 71, 47.7, and 47.7%, p=0.935) although donor quality was worse in the second period (DRI: 1.35±0.32 vs. 1.66±0.34, p<0.001). In the first period high-risk grafts did worse than low-risk grafts (5-year survival: 0 vs. 54.5%, p=0.002) while in the second period outcomes were similar (5-year survival: 48.6 vs. 56.7%, p=0.660). Donor age was the only independent donor factor for graft survival, with lower survival when using grafts from donors over 60-years-old. CONCLUSIONS: Graft quality in ReLT has worsened with time mainly because of older donors but nowadays the use of high-risk grafts in non-urgent ReLT is not associated with worse graft survival because of better perioperative management. Moreover of being selective on recipient conditions, care should be taken when using grafts from donors over 60-years-old for non-urgent ReLT.