Pulmonary hypertension and right ventricular involvement in hospitalised patients with COVID-19.

OBJECTIVE: To assess the prevalence, characteristics and prognostic value of pulmonary hypertension (PH) and right ventricular dysfunction (RVD) in hospitalised, non-intensive care unit (ICU) patients with coronavirus disease 2019 (COVID-19). METHODS: This single-centre, observational, cross-sectional study included 211 patients with COVID-19 admitted to non-ICU departments who underwent a single transthoracic echocardiography (TTE). Patients with poor acoustic window (n=11) were excluded. Clinical, imaging, laboratory and TTE findings were compared in patients with versus without PH (estimated systolic pulmonary artery pressure >35 mm Hg) and with versus without RVD (tricuspid annular plane systolic excursion <17 mm or S wave <9.5 cm/s). The primary endpoint was in-hospital death or ICU admission. RESULTS: A total of 200 patients were included in the final analysis (median age 62 (IQR 52-74) years, 65.5% men). The prevalence of PH and RVD was 12.0% (24/200) and 14.5% (29/200), respectively. Patients with PH were older and had a higher burden of pre-existing cardiac comorbidities and signs of more severe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (radiological lung involvement, laboratory findings and oxygenation status) compared with those without PH. Conversely, patients with RVD had a higher burden of pre-existing cardiac comorbidities but no evidence of more severe SARS-CoV-2 infection compared with those without RVD. The presence of PH was associated with a higher rate of in-hospital death or ICU admission (41.7 vs 8.5%, p<0.001), while the presence of RVD was not (17.2 vs 11.7%, p=0.404). CONCLUSIONS: Among hospitalised non-ICU patients with COVID-19, PH (and not RVD) was associated with signs of more severe COVID-19 and with worse in-hospital clinical outcome. TRIAL REGISTRATION NUMBER: NCT04318366.

Monoclonal B cell lymphocytosis in hepatitis C virus infected individuals.

BACKGROUND: Monoclonal B cell lymphocytosis (MBL) is a preclinical condition characterized by an expansion of clonal B cells in the absence of B lymphocytosis (BALC < 5 × 10(9)/L) in the peripheral blood, without clinical signs, suggestive of a lymphoproliferative disorder. B cell clonal expansions are also associated with hepatitis C virus (HCV) infection and they can evolve into lymphoproliferative disorders such as mixed cryoglobulinemia and non-Hodgkin lymphomas (NHL). The relationship between MBL and HCV infection has not been established yet. METHODS: By five-colour flow cytometry, we analyzed 123 HCV positive subjects with diagnosis of chronic hepatitis (94) or cirrhosis (29); 16 of those with cirrhosis had a diagnosis of hepatocellular carcinoma. RESULTS: MBL were identified in 35/123 (28.5%), at significantly higher frequency than in the general population. Sixteen/thirty-five were atypical-chronic lymphocytic leukemia (CLL) MBL (CD5(+), CD20(bright)), 13/35 were CLL-like MBL (CD5(bright), CD20(dim)), and 6/35 were CD5(-) MBL. Twenty-four/ninety-four (25.5%) patients affected by chronic hepatitis had MBL, whereas 11/29 (37.9%) patients with cirrhosis showed a B cell clone. A biased usage of IGHVgenes similar to HCV-associated NHL was evident. CONCLUSIONS: All three types of MBL can be identified in HCV-infected individuals at a higher frequency than in the general population, and their presence appears to correlate with a more advanced disease stage. The phenotypic heterogeneity is reminiscent of the diversity of NHL arising in the context of HCV infection. The persistence of HCV may be responsible for the dysregulation of the immune system and in particular of the B cell compartment.

Impact of type of liver resection on the outcome of colorectal liver metastases: a case-matched analysis.

BACKGROUND: Wedge resection (WR) for colorectal liver metastases (CLM) has become more common in an attempt to preserve liver parenchyma. However, some investigator have reported that WR is associated with a higher incidence of positive margin and an inferior survival compared with anatomic resection (AR) 1. OBJECTIVES: This study evaluated survival, margin status, and pattern of recurrence of patients with CLM treated with WR or AR. METHODS: We identified 208 consecutive patients, in a single institutional database from 1995 to 2004, who underwent either WR or AR. WR was defined as a nonanatomic resection and AR was defined as single resection of one or two liver segments. Patients with combined WR-AR and patients requiring resection of more than two segments or radiofrequency ablation were excluded from the analysis. RESULTS: One hundred six patients underwent WR and 102 patients had AR. There were no differences in the rate of positive surgical margin (P = 0.146), overall recurrence rates (P = 0.211), and patterns of recurrence between the two groups (P = 0.468). The median survival was 32 months for WR and 42 for AR, with 5-year survival rates of 29% and 27% respectively, with no significant difference (P = 0.308). Morbidity was similar between the two groups. CONCLUSIONS: WR is a safe procedure and does not disadvantage the patients in terms of tumor recurrence and overall survival.

Preoperative methylprednisolone administration maintains coagulation homeostasis in patients undergoing liver resection: importance of inflammatory cytokine modulation.

Alterations in hemostatic parameters are a common finding after major hepatic resection. There is growing evidence that inflammation has a significant role in inducing coagulation disarrangement that follows major surgery. To determine whether preoperative methylprednisolone administration has a protective effect against the development of coagulation disorders, we evaluated the effect of preoperative steroids administration on changes in hemostatic parameters and plasma levels of inflammatory cytokines in patients undergoing liver surgery. Seventy-three patients undergoing liver resection were randomized to a steroid group or to a control group. Patients in the steroid group received 500 mg of methylprednisolone preoperatively. Serum levels of coagulation parameters (prothrombin time, platelets, fibrinogen, plasma fibrin degradation products [D-dimer], antithrombin III) and inflammatory mediators (IL-6 and TNF-alpha) were measured before and immediately after the operation and on postoperative days 1, 2, and 5. Multivariate analysis was performed to identify factors related to the characteristics of the patients and surgery affecting coagulation parameters between the two groups. Decreases in antithrombin III, platelet count and fibrinogen levels, prolongation of prothrombin time, and increases in the plasma fibrin degradation products were significantly suppressed by the administration of methylprednisolone. Cytokines production was also significantly suppressed by the administration of methylprednisolone, and there was significant correlation between plasma levels of cytokines and coagulation alterations. These findings suggest that preoperative methylprednisolone administration inhibits the development of coagulation disarrangements in patients undergoing liver resection, possibly through suppressing the production of inflammatory cytokines.

A prospective evaluation of ultrasonic dissector plus harmonic scalpel in liver resection.

Several techniques have been described for safe dissection of the liver parenchyma. The aim of this study was to evaluate the feasibility and effectiveness of combining two different electronic devices, the ultrasonic dissector and the harmonic scalpel, during hepatic resection. One hundred consecutive patients who underwent liver resection between January and December 2004 were enclosed in the study. Patients requiring concomitant colic resection or biliary-enteric anastomosis were excluded from the study. Operative variables (type of procedure, operating time, Pringle time, blood losses, transfusions, and histological tumor exposure at the transection surface), hospital stay, and complications were recorded. The extent of hepatic resection was a minor resection in 31 and major in 69 cases. Median blood loss was 500 mL (range, 100-2000 mL) and the Pringle maneuver was used in 58 patients. Median operative time was 367 minutes (range, 150-660 minutes). Hepatic resection was performed in 32 cirrhotic livers. Surgical complications included one postoperative hemorrhage and two bile leaks. The overall morbidity and mortality rate was 14 and 1 per cent, respectively. In conclusion, the combined use of these electronic devices allows liver resection to be safely performed, even in cirrhotic patients, with the advantage of reducing surgical complications. A prospective randomized trial is needed to clarify the clinical benefits of liver resections performed combining these two devices.

Prospective randomized study of the benefits of preoperative corticosteroid administration on hepatic ischemia-reperfusion injury and cytokine response in patients undergoing hepatic resection.

BACKGROUND: Hepatic injury secondary to warm ischemia and reperfusion (I/R) remains an important clinical issue following liver surgery. The aim of this prospective, randomized study was to determine whether steroid administration may reduce liver injury and improve short-term outcome. PATIENTS AND METHODS: Forty-three patients undergoing liver resection were randomized to a steroid group or a control group. Patients in the steroid group received 500 mg of methylprednisolone preoperatively. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, anti-thrombin III (AT-III), prothrombin time (PT), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-alpha) were compared between the two groups. Length of stay and type and number of complications were recorded. RESULTS: Postoperative serum levels of ALT, AST, total bilirubin, and inflammatory cytokines were significantly lower in the steroid group than in controls. The postoperative level of AT-III in the control group was significantly lower than in the steroid group (ANOVA p < 0.01). The incidence of postoperative complications in the control group tended to be significantly higher than that in the steroid group. CONCLUSION: These results suggest that steroid pretreatment represents a potentially important biologic modifier of I/R injury and may contribute to maintenance of coagulant/anticoagulant homeostasis.

"Technological" approach versus clamp crushing technique for hepatic parenchymal transection: a comparative study.

We evaluated the feasibility and effectiveness of combining two different electronic devices, the ultrasonic dissector (UD) and the harmonic scalpel (HS), during hepatic resection. One hundred consecutive patients underwent liver resection using UD plus HS between January and December 2004 (UD + HS group). The ultrasonic dissector was used to fracture liver parenchyma and the uncovered vessel was sealed using the HS. Surgical outcomes were compared with 100 consecutive patients who underwent liver resection using the clamp crushing method. Operative variables, postoperative liver function, hospital stay, and type and number of complications were compared. The two groups were equivalent in term of demographic and pathologic variables. The UD + HS group had a decreased blood loss (500 ml versus 700 ml, P = 0.005), number of patients transfused (22 versus 39, P = 0.009), tumor exposure at the transection surface (4 versus 12, P = 00.012), and hospital stay (7 versus 8.5 days, P = 0.020). Postoperative major complications, in particular, fluid collection and biliary fistula, were significantly less frequent in the UD + HS group (2 versus 9, P = 0.030). A longer operative time was recorded in the UD + HS group (385 versus 330 minutes, P = 0.001). The combined use of UD with HS allows liver resection to be safely performed, with the advantage of reducing blood losses and surgery-related complications. The only major disadvantage may be a longer transection time.

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.

Treatment of non-endemic hepatolithiasis in a Western country. The role of hepatic resection.

INTRODUCTION: The aim of this study was to assess the safety and the efficacy of hepatic resective surgery in the treatment of single lobe hepatolithiasis. PATIENTS AND METHODS: Retrospective analysis and comparison between hepatic resections in patients with hepatolithiasis (hepatolithiasis group [HG]) and liver masses (control group [CG]). Seventeen consecutive Caucasian patients with single lobe hepatolithiasis (HG) and 30 patients with liver masses without chronic liver disease and previous chemotherapy (CG), were operated during the 5-year period 2000-2005, inclusive. Major hepatic resections including 4 right hepatectomies, 10 left hepatectomies, and 3 left lateral sectionectomy in HG, and 12 right hepatectomies, 3 extended right hepatectomy, 5 left hepatectomies, 4 left lateral sectionectomy, 5 bisegmentectomy, and 1 mesohepatectomy in CG. The main outcome measures were: type and length of surgical procedures, intra- and postoperative blood losses and transfusions (packed red blood cells [PRBC] and fresh frozen plasma [FFP]), intra- and postoperative course and complications (within 30 days of the operation), length of hospitalisation, histopathology, and recurrence of hepatolithiasis. RESULTS: Mean operation time was 6.21 +/- 2.38 h in HG versus 7.10 +/- 2.21 h in CG (P = 0.33). Mean intra-operative blood loss in CG was higher than in HG (1010 +/- 550 ml versus 560 +/- 459 ml; P = 0.035). The other variables considered in the two groups were not statistically different. Intra-operative transfusion were 0.50 +/- 0.85 units in HG versus 1.35 +/- 2.25 units of PRBC in CG (P = 0.06), and 0.66 +/- 1.34 units in HG versus 0.68 +/- 1.20 units of FFP in CG (P = 0.44), respectively. No cases of death were registered. Postoperative complications occurred in 12 patients (25.5%) - 5 cases (10.6%) in HG and 7 cases (14.8%) in CG (P = 0.18). Mean postoperative transfusions were 0.47 +/- 1.24 units in HG versus 1.10 +/- 1.18 units of PRBC in CG (P = 0.35), and 0.65 +/- 1.40 units in HG versus 0.46 +/- 0.82 units of FFP in CG (P = 0.25), respectively. Difference in median hospitalisation was not statistically significant (14 +/- 10 days versus 12 +/- 9 days; P = 0.28). Histopathology showed cholangiocarcinoma in 2 cases (11.7%). During the follow-up period (range, 5-127 months; mean, 50.4 +/- 41.9 months), 1 patient had lithiasis recurrence and 1 patient died for the co-existing cholangiocarcinoma. CONCLUSIONS: Hepatic resection is the treatment of choice in patients with single lobe hepatolithiasis. An early indication for surgery may reduce the mortality/morbidity rates of hepatic resection for hepatolithiasis.

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.

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.

Impact of advanced age on the outcome of liver resection.

The aim of this retrospective study was to evaluate the influence of age on the outcome of liver resection. A total of 129 consecutive liver resections were divided into two groups: > or = 70 years old [old group (O-group)] and < 70 years old [young group (Y-group)]. The two groups were first compared for the variables potentially affecting the postoperative course, including diagnosis, concomitant diseases, previous abdominal surgery, type of operation (major or minor resection), associated procedures, presence and length of portal clamping, intraoperative blood losses and transfusions, and length of operation. The outcome of liver resections was evaluated in terms of postoperative mortality, morbidity, transfusions, and length of hospitalization. The Y-group included 97 resections in 95 patients, aged 55.9 +/- 10.5 years (mean +/- SD; range: 23-69 years), and the O-group included 32 resections in 32 patients, aged 73.7 +/- 3.2 years (mean +/- SD; range: 70-82 years. The O-group included more hepatocellular carcinomas (46.9% versus 20.6%, p = 0.002) and cardiovascular diseases (15.2% versus 1.0%, p = 0.004). The two groups were comparable (p > 0.05) when evaluated for all other listed variables. As regards the postoperative outcome, the length of hospitalization was similar (median, range: 9.5 days, 5-60 days in the Y-group and 9 days, 5-48 days in the O-group) and the need for postoperative transfusions were not statistically different. Mortality included one case among young patients, while no deaths were recorded among elderly patients. Postoperative morbidity was higher in Y-group than in O-group (21.6% versus 9.4%, p = 0.2). In conclusion, the age factor does not negatively affect the outcome of liver resections.