Antonio Pesce

Bile duct injury during laparoscopic cholecystectomy without intraoperative cholangiography: a retrospective study on 1,100 selected patients.

Background: Whether to routinely or selectively use intraoperative cholangiography (IOC) during laparoscopic cholecystectomy (LC) has been a controversial issue for many years. Many authors maintain that IOC decreases the rate of biliary complications such as bile duct injuries, biliary leak, and missed common bile duct (CBD) stones. However, in contrast to these claims, many centers have opted to perform LC without IOC. In this retrospective study, the results of a series of 1,100 LCs, all of which involved major biliary complications and which were performed without the use of IOC, were reviewed. Methods: Data from 1,100 selected patients (728 females and 372 males) undergoing LC without the use of IOC from January 2003 to November 2011 were analyzed. One hundred and seventy LCs were performed by young surgeons during the learning curve, and 930 by surgeons with over 10 years of experience. Two techniques were used to create pneumoperitoneum: the Veress technique in 319 cases (29%) and the Hasson technique in the remaining 781 cases (71%). Patients with a suspicion of CBD stones were excluded from the study. Results: Two CBD injuries (0.18%) and three biliary leaks (0.27%) were detected among this group. Thirty-three patients (3%) needed conversion to open cholecystectomy. Missed CBD stones were reported in 4 cases (0.36%). There was no postoperative mortality. Conclusion: LC can be performed safely without the use of IOC and with acceptable low rates of biliary complications. An accurate preoperative evaluation of clinical risk factors, precise operative procedures, and conversion to an open approach in doubtful cases are important measures which must be taken to prevent CBD injury.

Identification of novel targets for the diagnosis and treatment of liver fibrosis

Liver fibrosis is characterized by the excessive deposition of extracellular matrix (ECM) in the hepatic parenchyma and represents an intrinsic response to chronic injury, maintaining organ integrity when extensive necrosis or apoptosis occurs. Hepatic stellate cells (HSCs) are the major cell type responsible for liver fibrosis. Following liver injury, HSCs become activated and transdifferentiate into myofibroblasts (MFBs) that lead to intrahepatic ECM accumulation. In the present study, we performed a meta‑analysis of datasets which included whole-genome transcriptional data on HSCs in the quiescent and activated state from two different rodent species and identified commonly regulated genes. Several of the genes identified, including ECM components, metalloproteinases and growth factors, were found to be well‑known markers for HSC activation. However, other significant genes also appeared to play important roles in hepatic fibrosis. The elucidation of the molecular events underlying HSC activation may be key to the identification of potential novel pharmacological targets for the prevention and treatment of liver fibrosis.

Ultrasound as point of care in management of polytrauma and its complication

PurposeTraumatic injuries constitute a major risk for patients in emergency units. Point-of-care ultrasound may be a determinant in reducing the deleterious impact of complications and in prognosis.MethodsWe describe the case of a 28-year-old female who reported cranial trauma, abdominal and thoracic trauma, and suspected bilateral fracture of the femur.ResultsUltrasound was useful for evaluating and monitoring multiple organ failure.ConclusionCombining cost-effective advantages with bedside real-time imaging, ultrasound is a powerful adjunct to standard clinical assessment in the management of polytrauma when it is administered at the point of care.SommarioScopole patologie traumatiche rappresentano il maggiore rischio dei pazienti nelle Unità di Emergenza. L’ecografia consentendo una diagnosi precoce sia del tipo di trauma sia delle complicanze che da questo potrebbero derivane, può rappresentare un mezzo importante per la prognosi e per l’eventuale terapia.MetodiA tale scopo, noi presentiamo un caso paradigmatico di una paziente di 28 anni che, a seguito di un incidente, aveva riportato dei traumi al cranio, all’addome e al torace e sospetta frattura bilaterale al femore. Al momento del ricovero la paziente era monitorizzata tramite ecografia. I dati venivano confermati sia dalla sintomatologia clinica obiettiva, sia dalla tomografia assiale computerizzata.Risultatol’uso dell’ecografia ha consentito una diagnosi precoce non solo del tipo di trauma, ma anche ha permesso un corretto intervento terapeutico ed un monitoraggio anche dell’attività cardiaca.ConclusioneL’ecografia presenta vantaggi dal punto di vista costo-beneficio ed è utile sia ai fini diagnostici, sia ai fini terapeutici.

Does transient elastography (FibroScan®) have a role in decision making in hepatocellular carcinoma?

OBJECTIVES Portal hypertension has been reported as a negative prognostic factor and a relative contraindication for liver resection. This study considers a possible role of fibrosis evaluation by transient elastography (FibroScan(®)) and its correlation with portal hypertension in patients with cirrhosis, and discusses the use of this technique in planning therapeutic options in patients with hepatocellular carcinoma (HCC). METHODS A total of 77 patients with cirrhosis, 42 (54.5%) of whom had HCC, were enrolled in this study during 2009-2011. The group included 46 (59.7%) men. The mean age of the sample was 65.2 years. The principle aetiology of disease was hepatitis C virus (HCV)-related cirrhosis (66.2%). Liver function was assessed according to Child-Pugh classification. In all patients liver stiffness (LS) was measured using FibroScan(®). The presence of portal hypertension was indirectly defined as: (i) oesophageal varices detectable on endoscopy; (ii) splenomegaly (increased diameter of the spleen to ≥ 12 cm), or (iii) a platelet count of <100,000 platelets/mm(3). RESULTS Median LS in all patients was 27.9 kPa. Portal hypertension was recorded as present in 37 patients (48.1%) and absent in 40 patients (51.9%). Median LS values in HCC patients with and without portal hypertension were 29.1 kPa and 19.6 kPa, respectively (r = 0.26, P < 0.04). Liver stiffness was used to implement the Barcelona Clinic Liver Cancer algorithm in decisions about treatment. CONCLUSIONS   The evaluation of liver fibrosis by transient elastography may be useful in the follow-up of patients with cirrhosis and a direct correlation with portal hypertension may aid in the evaluation of surgical risk in patients with HCC and in the choice of alternative therapies.

Involvement of the Nrf2/HO‐1/CO axis and therapeutic intervention with the CO‐Releasing Molecule CORM‐A1, in a murine model of Autoimmune Hepatitis

Concanavalin A (ConA)‐induced hepatitis is an experimental model of human autoimmune hepatitis induced in rodents by i.v. injection of Con A. The disease is characterized by increase in serum levels of transaminases and massive immune infiltration of the livers. Type 1, type 2, and type 17 cytokines play a pathogenic role in the development of ConA‐induced hepatitis. To understand further the immunoregulatory mechanisms operating in the development and regulation of ConA‐induced hepatitis, we have evaluated the role of the anti‐inflammatory pathway Nrf2/HO‐1/CO (Nuclear Factor E2‐related Factor 2/Heme Oxygenase‐1/Carbon Monoxide) in this condition and determined whether the in vivo administration of CO via the CO‐releasing molecule (CORM) CORM‐A1, influences serological and histological development of Con‐A‐induced hepatitis. We have firstly evaluated in silico the genes belonging to the Nrf2/HO‐1/CO pathway that are involved in the pathogenesis of autoimmune hepatitis (AIH). The data obtained from the in silico study demonstrate that a significant number of genes modulated in the liver of ConA‐challenged mice belong to the Nrf2 pathway; on the other hand, the administration of CORM‐A1 determines an improvement in several sero‐immunological and histological parameters, and it is able to modulate genes identified by the in silico analysis. Collectively, our data indicate that the Nrf2/HO‐1/CO pathway is fundamental for the regulation of the immune responses, and that therapeutic intervention aimed at its modulation by CORM‐A1 may represent a valuable strategy to be considered for the treatment of autoimmune hepatitis in humans.

Evaluation of fibrosis in cirrhotic elderly patients with HCC

BackgroundHepatocellular carcinoma (HCC) is usually associatedwith liver cirrhosis and is the principal cause of deathamong patients with cirrhosis [1]. Apart from livertransplantation that may cure both conditions, treat-ment of HCC and cirrhosis is complex because of theneed to be oncologically radical but simultaneously con-servative. Hepatectomy is considered an invasiveapproach and has a marginal role in the treatment ofHCC [2,3]. The value of hepatic fibrosis is considered apredictive factor of outcome in patients with HCCundergoing liver resection [4].Materials and methodsA retrospective analysis of 77 cirrhotic patients, 42 ofthem with hepatocellular carcinoma, observed from2008 to 2010 was performed. The mean age was 65.2years old with 46 men and 31 women. As regards cir-rhosis etiology, 51 patients presented cirrhosis HCV-related, 9 HBV-related, 3 alcohol-related, 2 HBV-HDVco-infections and 12 other etiology. Liver function wasassessed according to the Child-Pugh classification: 60patients were in Child A, 13 in Child B and 4 in ChildC. In all patients liver stiffness measurement (LSM) wasperformed using transient elastography (Fibroscan

Predictive Value of the Number of Harvested Lymph Nodes and Cut-Off for Lymph Node Ratio in the Prognosis of Stage II and III Colorectal Cancer Patients

ABSTRACT Purpose/aim: The appropriate staging of colorectal cancer requires at least 12 lymph nodes to be sampled. We evaluated whether lymph node sampling (LNS) and lymph node ratio (LNR) can predict the prognosis of stage II-III patients. Materials and methods: This is a retrospective study on 432 patients classified in LNS ≥12 and LNS <12. Disease-free survival (DFS) was computed using the Kaplan–Meier method. We stratified stage III patients into 4 quartiles base on LNR values. To determine the optimal LNR cut-off, receiver operating characteristic (ROC) curve analysis was performed. Results: There was a positive association between the number of lymph node sampled and the number of metastatic lymph nodes (p < 0.01). Among stage II patients, the DFS was 81% for LNS ≥ 12 and 72% for LNS < 12 (p = 0.158). Among stage III patients, the DFS was 58% (p < 0.001). We found a significant association between LNR quartiles and relapse in stage III patients but only in the LNS ≥ 12 group. ROC curve analysis indicated an ideal LNR cut-off value at 0.194 (sensitivity 65% and specificity 61%). The DFS of patients with LNR below 0.194 was 71%, and that of patients with LNR above 0.194 was 45% (log-rank test, p < 0.001). In the patients with LNS ≥ 12, the cut-off of 0.257 could predict recurrence (specificity 86%). Conclusions: Stage II patients with LNS < 12 tend to have shorter DFS than stage II patients with LNS ≥ 12. In stage III patients, an appropriate LNR cut-off is a better prognostic predictor than LNR quartile, especially in patients with LNS ≥ 12.

Dystopic retrohepatic gallbladder and cholecysto-choledocho lithiasis: the rendez-vous and indocyanine green fluorescence

Laparoscopic cholecystectomy is a well‐known procedure for the treatment of most gallbladder diseases. Sometimes, it could be very difficult, in the presence of aberrations regarding the cystic duct, the cystic artery, or the gallbladder itself. Fluorescence laparoscopy using indocyanine green could be very useful for all the situations of anatomy aberrations.

Metastatic hepatocellular carcinoma to the occipito‐cervical junction: a unique case and literature review

A 53-year-old woman presented with a 2-month history of cervical pain without any evidence of skeletal fractures at axial X-ray. The patient denied any significant medical problem, neither any prior history of hepatic disease or chronic alcoholism. She reported a previous laparoscopic cholecystectomy for cholelithiasis. Laboratory tests revealed an increase of alkaline phosphatase (226 U/L) and gamma-GT (240 U/L) levels; the alpha-fetoprotein value was 11.5 UI/mL. An abdominal ultrasonography and computed tomography (CT) scan were performed. CT scan identified a large mass in the right lobe of the liver measuring with 14 cm in its greatest diameter, which infiltrated the right and middle hepatic veins, as shown in Figure 1a. The radiological findings were not consistent with the diagnosis of hepatocellular carcinoma (HCC). No portal vein thrombosis was observed. However, cervical spine CT and dorsal-cervical-magnetic resonance imaging were performed showing an osteolytic lesion in the right C1 lateral mass, invading the anterior arc, the para-vertebral muscles and above the occipitocervical junction (Fig. 1b). There was no evidence of spinal cord compression (Fig. 1c). After a multidisciplinary evaluation, the patient underwent neurosurgical procedure of osteosynthesis on C2 and C3. During surgery, a biopsy of the soft tissue mass in C1 was performed. Histological diagnosis revealed a metastatic carcinoma with solid and trabecular growth patterns. Immunohistochemical analyses showing a focal positivity for anti-hepatocyte and anti-carcino-embryonic antigen antibodies were consistent with the diagnosis of HCC metastasis, as shown in Figure 2. There was also a marked and widespread positivity for cytokeratin-19. The biopsy of the liver mass confirmed the presence of a moderately differentiated HCC. A lateral cervical spine X-ray at 1 month revealed no evidence of failure (Fig. 1d) and clinically the patient presented an improvement of cervical pain. Therefore, the patient was discharged, succumbing to her metastatic disease 3 months later. HCC represents the most common primary tumour of the liver and the fifth most common cancer in the world. We describe, to the best of our knowledge, the first case of HCC in a female patient without any evidence of underlying liver disease, who presented with unknown isolated HCC metastasis to the occipito-cervical junction C0–C1 and cervical instability due to tumour infiltration and destruction of the atlanto-occipital joint. A recent systematic review about metastatic HCC to the spine identified a prevalence of cervical localizations for metastasis in about 14.5% of patients, whereas thoracic and lumbar localization were, respectively, in 44.7 and 22.4%. Among patients with the cervical spine metastases, the results showed that the most frequent symptoms at the time of the diagnosis were neck pain and neurologic symptoms in 70% of cases, followed by pathological fractures in 25%. Metastatic involvement of the atlanto-occipital junction is rare with only 16 cases previously reported (Table 1). Specifically, the most frequent primary tumour was lung cancer in six cases, following by thyroid cancer in three patients. Considering the poor prognosis of metastatic vertebral disease, especially in advanced-stage patients, the goal of treatment for such lesions is not an anterior radical tumour resection but the palliation of the symptoms, which includes pain control, posterior occipito-cervical stabilization, prevention of neurological deterioration and the maintenance of mobility. In the majority of cases, patients with metastatic disease at the atlanto-occipital joint experience a reduction in upper neck pain following occipito-cervical fixation. In our patient, the mechanical

Efficacy of the Laparoendoscopic "Rendezvous" to Treat Cholecystocholedocholithiasis in 210 Consecutive Patients: A Single Center Experience

Objective: The simultaneous laparoendoscopic “rendezvous” (LERV) represents an alternative to sequential or totally laparoscopic approaches for patients affected by cholecystocholedocholithiasis. The aim of this study was to analyze the results in a large series of 210 consecutive patients. Materials and Methods: From 2002 to 2016 all patients affected by cholecystocholedocholithiasis were treated with a standardized “tailored” LERV. The relevant technical features of the procedure were recorded. An analysis of feasibility, effectiveness in stone clearance, and safety was performed. Results: Among 214 patients with common bile duct stones, 210 were treated with LERV and 4 with open rendezvous approach. Intraoperative cholangiography confirmed common bile duct stones in 179 patients (85.2%) or sludge in 18 (8.5%) and in 98.9% stone clearance was obtained endoscopically. Endoscopic papilla cannulation was feasible in 161 patients (76.7%), whereas in 49 (23.3%) a transcystic guidewire was needed. The overall LERV feasibility was 96.6%. The conversion rate to open surgery was 3.3%. Minor morbidity was observed in 1.9% of cases, mortality in 0.47%, and the mean hospital stay was 4.3 days. Conclusions: These results confirm the high effectiveness of LERV. This approach to treat cholecystocholedocholithiasis should be preferred and therefore implemented where a strong collaboration between surgeons and endoscopists is possible.