Liver resections in over‐75‐year‐old patients: Surgical hazard or current practice?

OBJECTIVES: To assess the safety of hepatic resections in the very old patient by comparing the outcome in patients younger and older than 75 years. METHODS: Thirty-two resections in 31 patients > or =75 years (Over-75 Group) were compared with 164 resections in 162 patients <75 years (Control Group). Indications for resection, concomitant diseases, previous abdominal surgery, type of resection, associated surgical procedures, use/length of portal clamping, intra-operative blood losses and transfusions, and length of operation were preliminarily compared. The outcome was evaluated in terms of post-operative mortality, morbidity, transfusions, and postoperative hospitalization. RESULTS: Mean age was 76.0 +/- 2.3 years (range 75-83) in the Over-75 Group and 58.4 +/- 10.7 years (range 23-74) in the Control Group. The over-75 group included more hepatomas (43.8% vs. 26.8%, P = 0.09), chronic liver disease (31.3% vs. 28.7%, P = 0.03) and concomitant diseases (62.5% vs. 32.9%, P = 0.002). The two groups were comparable (P = n.s.) when evaluated for all other variables. The 30-day mortality rate was 3.6% in the Control Group and none in the Over-75 Group. Postoperative surgical complications occurred in 37 patients (22.6%) in the Control Group and 1 patient (3.1%) in the Over-75 Group, with statistically significant differences (P = 0.01), and incidence of medical complications was 13.4% in the Control Group and 3.1% in the Over-75 Group. Median postoperative hospitalization and transfusions were not statistically different. CONCLUSIONS: Hepatic resections in over-75-year-old patients are not a surgical hazard and may be carried out relatively safely as long as an accurate selection of the patient is performed.     

Cancer risk in oil refinery workers: a pooled mortality study in Italy

Background:Oil refinery workers are exposed to several well-established carcinogens and working in this type of industry has been classified by IARC as probable carcinogen to humans (Group 2A).Objectives:To examine the mortality experience of workers employed in four Italian oil refineries.Methods:The cohort included 5112 male workers ever employed between 1949 and 2011. The average follow-up period was 49 years. Standardized mortality ratios (SMR) and 95% Confidence Intervals (CI) were calculated using as reference age-gender-calendar specific regional rates. Analyses by duration of employment and latency were performed.Results:In the whole cohort, pleural cancer (6 deaths, SMR 1.59; 95% CI 0.71-3.53), brain cancer (14 deaths, SMR 1.47; 95% CI 0.87-2.49) and lymphatic leukemia (LL) (8 deaths, SMR 1.81; 95% CI 0.91-3.62) showed increased risks. All pleural cancers occurred after 10 years of latency and the highest risk was observed among workers with duration ≥20 years; the brain cancer excess was confined in the shortest duration and latency. The LL (and chronic lymphatic leukemia in particular) excess regarded workers with latency and duration longer than 20 years. Four deaths from acute myeloid leukemia (AML) were observed and all occurred after 20 years of latency (SMR 1.55, 95% CI 0.58-4.12); a two-fold-increased risk was observed in the longest duration. No increased risk for skin cancer has been observed in our study population.Conclusion:Our findings are consistent with recent evidence of an increased mortality from pleural and hematopoietic malignancies (AML and LL) among oil refinery workers. However, the lack of individual quantitative exposure data and the small number of observed events prevent the identification of the possible causal role of individual chemicals, including benzene, especially at the current very low exposure levels.Key words: Cohort study, cancer mortality, benzene, petrochemical industry, standardized mortality ratios     

Results of Preoperative Hepatic Arterial Infusion Chemotherapy in Patients Undergoing Liver Resection for Colorectal Liver Metastases

Background Although hepatic artery infusion chemotherapy (HAIC) of floxuridine (FUDR) for colorectal liver metastases (CLM) can produce high response rates, data concerning preoperative HAIC are scarce. The aim of this study was to assess the feasibility and results of liver resection after preoperative HAIC with FUDR. Methods Between 1995 and 2004, 239 patients with isolated CLM received HAIC in our institution. Fifty of these patients underwent subsequent curative liver resection (HAIC group). Short- and long-term results of the HAIC group were compared with the outcomes of 50 patients who underwent liver resection for CLM without preoperative chemotherapy. Results Postoperative morbidity rate were comparable between the two groups. Overall disease-free survival at 1 and 3 years after hepatectomy were 77.5% and 57.5% in the HAIC group and 62.9% and 37% in the control group (P = .036). Overall survival from diagnosis of CLM at 1, 3, and 5 years were 97%, 59%, and 49% in the HAIC group versus 94%, 48%, and 35% in the control group (P = .097). When patients were stratified according to clinical-risk scoring (CRS) system, patients with more advanced disease at the time of liver resection (CRS ≥3) had a median survival of 41 months in the HAIC group (n = 37) and 35 months in the control group (n = 34) (P = .031). Conclusions HAIC of FUDR does not negatively affect the outcome of subsequent liver resection. Preoperative HAIC of FUDR may reduce liver recurrence rate and improve long-term survival in patients with more advanced liver disease. Part of this article was presented at the International Hepato-Pancreato-Biliary Association, 7th World Congress in Edinburgh, Scotland, September 3–7, 2006.     

Analysis of Prognostic Factors Influencing Long-term Survival After Hepatic Resection for Metastatic Colorectal Cancer

Background The aim of this study was to analyze the prognostic factors associated with long-term outcome after liver resection for colorectal metastases. The retrospective analysis included 297 liver resections for colorectal metastases. Methods The variables considered included disease stage, differentiation grade, site and nodal metastasis of the primary tumor, number and diameter of the lesions, time from primary cancer to metastasis, preoperative carcinoembryonic antigen (CEA) level, adjuvant chemotherapy, type of resection, intraoperative ultrasonography and portal clamping use, blood loss, transfusions, complications, hospitalization, surgical margins status, and a clinical risk score (MSKCC-CRS). Results The univariate analysis revealed a significant difference (p < 0.05) in overall 5-year survival rates depending on the differentiation grade, preoperative CEA >5 and >200 ng/ml, diameter of the lesion >5 cm, time from primary tumor to metastases >12 months, MSKCC-CRS >2. The multivariate analysis showed three independent negative prognostic factors: G3 or G4 grade, CEA >5 ng/ml, and high MSKCC-CRS. Conclusions No single prognostic factor proved to be associated with a sufficiently disappointing outcome to exclude patients from liver resection. However, in the presence of some prognostic factors (G3–G4 differentiation, preoperative CEA >5 ng/ml, high MSKCC-CRS), enrollment of patients in trials exploring new adjuvant treatments is suggested to improve the outcome after surgery.     

A risk score for predicting perioperative blood transfusion in liver surgery

BACKGROUND: It would be desirable to predict which patients are most likely to benefit from preoperative autologous blood donation. This aim of this study was to develop a point scoring system for predicting the need for blood transfusion in liver surgery. METHODS: The medical records of 480 consecutive patients who underwent hepatic resection were analysed. The data set was split randomly into a derivation set of two-thirds and a validation set of one-third. Univariable analysis was carried out to determine the association between clinicopathological factors and blood transfusion. Significant variables were entered into a multiple logistic regression model, and a transfusion risk score (TRS) was developed. The accuracy of the system was validated by calculating the area under the receiver-operator characteristic (ROC) curve. RESULTS: Factors associated with blood transfusion in multivariable analysis included preoperative haemoglobin concentration below 12.5 g/dl, largest tumour more than 4 cm, need for exposure of the vena cava, need for an associated procedure, and cirrhosis. Each variable was assigned one point, and the total score was compared with the transfusion status of each patient in the validation set. The TRS accurately predicted the likelihood of blood transfusion. In the validation set the area under the ROC curve was 0.89. CONCLUSION: Use of the TRS could lead to substantial saving by improving the cost-effectiveness of the autologous blood donation programme.     

Impact of preoperative steroids administration on ischemia-reperfusion injury and systemic responses in liver surgery: a prospective randomized study.

Hepatic injury secondary to warm ischemia-reperfusion (I/R) injury and alterations in haemostatic parameters are often unavoidable events after major hepatic resection. The release of inflammatory mediator is believed to play a significant role in the genesis of these events. It has been suggested that preoperative steroid administration may reduce I/R injury and improve several aspects of the surgical stress response. The aim of this prospective randomized study was to investigate the clinical benefits on I/R injury and systemic responses of preoperatively administered corticosteroids. Seventy-six patients undergoing liver resection were randomized either to a steroid group or to a control group. Patients in the steroid group received preoperatively 500 mg of methylprednisolone. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, coagulation parameters, and inflammatory mediators, interleukin 6 and tumor necrosis factor alpha were compared between the 2 groups. Length of stay, and type and number of complications were recorded as well. Postoperative serum levels of ALT, AST, total bilirubin, and inflammatory cytokines were significantly lower in the steroid than in the control group at postoperative days 1 and 2. Changes in hemostatic parameters were also significantly attenuated in the steroid group. In conclusion, the incidence of postoperative complications in the steroid group tended to be significantly lower than the control group. It is of clinical interest that preoperative steroids administration before major surgery may reduce I/R injury, maintain coagulant/anticoagulant homeostasis, and reduce postoperative complications by modulating the inflammatory response.     

Reduced severity of liver ischemia/reperfusion injury following hepatic resection in humans is associated with enhanced intrahepatic expression of Th2 cytokines.

BACKGROUND: Based on previous studies in experimental models, pro-inflammatory Th1 cytokines (i.e. TNF-alpha and IFN-gamma) are thought to play a pathogenic role in hepatic ischemia/reperfusion injury, while anti-inflammatory Th2 cytokines (i.e. IL-4 and IL-10) have been associated with reduced liver disease severity. To test the relevance of these concepts in humans, cytokine expression profiles were characterized in liver biopsies from patients undergoing hepatic resection following intermittent portal clamping. METHODS: Twelve patients were analyzed for the intrahepatic expression of TNF-alpha, IFN-gamma, IL-4 and IL-10 before and about 90min after the last reperfusion. In addition, parameters of liver damage including sALT and serum levels of TNF-alpha were analyzed at 2, 24 and 48h after surgery. RESULTS: When compared with pre-reperfusion liver specimens, all post-reperfusion biopsies showed significantly increased levels of TNF-alpha and IFN-gamma mRNAs. Conversely IL-4 and IL-10 mRNA levels were significantly increased in only seven patients. A negative correlation was observed between Th2 cytokines (IL-4, IL-10) and ALT and serum levels of TNF-alpha. Furthermore, the presence of hepatic steatosis was significantly associated with lower intrahepatic contents of IL-4 and IL-10. CONCLUSIONS: The results suggest that the local early expression of Th2 cytokines may contribute to attenuate liver injury following ischemia reperfusion in humans. The early imbalance between pro- and anti-inflammatory cytokines seen in steatotic liver subjected to I/R could explain, at least partially, the decreased tolerance of steatotic livers to I/R injury.