Model to predict major complications following liver resection for HCC in patients with metabolic syndrome.

BACKGROUND: Metabolic syndrome (MS) is rapidly growing as risk factor for HCC. Liver resection for HCC in patients with MS is associated with increased postoperative risks. There are no data on factors associated with postoperative complications. AIMS: The aim was to identify risk factors and develop and validate a model for postoperative major morbidity after liver resection for HCC in patients with MS, using a large multicentric Western cohort. MATERIALS AND METHODS: The univariable logistic regression analysis was applied to select predictive factors for 90 days major morbidity. The model was built on the multivariable regression and presented as a nomogram. Performance was evaluated by internal validation through the bootstrap method. The predictive discrimination was assessed through the concordance index. RESULTS: A total of 1087 patients were gathered from 24 centers between 2001 and 2021. Four hundred and eighty-four patients (45.2%) were obese. Most liver resections were performed using an open approach (59.1%), and 743 (68.3%) underwent minor hepatectomies. Three hundred and seventy-six patients (34.6%) developed postoperative complications, with 13.8% major morbidity and 2.9% mortality rates. Seven hundred and thirteen patients had complete data and were included in the prediction model. The model identified obesity, diabetes, ischemic heart disease, portal hypertension, open approach, major hepatectomy, and changes in the nontumoral parenchyma as risk factors for major morbidity. The model demonstrated an AUC of 72.8% (95% CI: 67.2%-78.2%) ( https://childb.shinyapps.io/NomogramMajorMorbidity90days/ ). CONCLUSIONS: Patients undergoing liver resection for HCC and MS are at high risk of postoperative major complications and death. Careful patient selection, considering baseline characteristics, liver function, and type of surgery, is key to achieving optimal outcomes.

Impact of Aspirin on clinical outcome in advanced HCC patients receiving sorafenib and regorafenib.

BACKGROUND AND AIM: The aim of our retrospective study is to evaluate the prognostic significance of aspirin in patients with advanced HCC treated with sorafenib. METHODS: 304 patients with HCC,consecutively treated with sorafenib from May 2007 to September 2018, were included in the clinical study. Of Them 93 patients token aspirin. Progression-free survival (PFS)and overall survival (OS)were estimated with the Kaplan-Meier method and compared with the log-rank test. RESULTS: The concomitant use of sorafenib and aspirin was associated with a median OS of 18.3 months compared to 8.8 months of patients who did not receive aspirin (HR 0.57; P < 0.0001). The concomitant use of sorafenib and aspirin was associated with a median PFS of 7.3 months compared to 3.0 months of patients who did not receive aspirin (HR 0.61; P = 0.0003). In the multivariate analysis, the use of aspirin maintained an independent prognostic value for OS(HR 0.61; P = 0.0013). In second line the concomitant use of regorafenib and aspirin was associated with a median OS of 16.9 months compared to 8.0 months of patients who did not receive aspirin (HR 0.30; P = 0.02). CONCLUSION: Globally, our data seem to suggest that aspirin use may improve the clinical outcome of patients with advanced hepatocellular carcinoma receiving sorafenib and regorafenib.

A Translational Approach to Standardization of Machine Perfusion Adoption in Ex Vivo Liver Resection.

BACKGROUND: Hepatic resection represents the best treatment for primary and metastatic liver tumors but is not always feasible. In early 1980, Piclmayr described a complex liver resection technique, termed "ex vivo liver resection," for the treatment of locally advanced tumors not conventionally resectable. The authors approached this technique with translational research in a preclinical setting and then similarly reproduced it in human patients. METHODS: In the swine median xyphopubic laparotomy, the liver was mobilized to expose the vena cava. A temporary porto-caval shunt was previously prepared on the back table using a segment of thoracic aorta, and a vascular anastomosis between the supra-hepatic vena cava and a caval graft was quickly performed. The liver was placed in a machine perfusion system and continuously perfused for 2 h for its final implantation orthotopically in the same animal. The anastomoses were performed as usual. Based on this experience, the intervention was reproduced in the human model of a 39-year-old woman affected by large intrahepatic cholangiocarcinoma considered unresectable.' RESULTS: All animals survived the procedure. The peak aspartate aminotransferase level (460 ± 87 U/L) was recorded 60 min after reperfusion. Lactate levels flared up for 120 min (3.6 ± 0.2 mmol/L). In the clinical case, the postoperative period was uneventful, and the patient was discharged on day 22. CONCLUSIONS: The described procedure is feasible only for surgeons with a transplantation background. The study showed that this translational approach enhances the surgeon's ability to perform the intervention systematically in a shorter time and with a good outcome.

Rare Neoplasm Mimicking Neuoroendocrine Pancreatic Tumor: A Case Report of Solitary Fibrous Tumor with Review of the Literature.

BACKGROUND: Solitary fibrous tumors (SFTs) are rare biological entities described mainly in the pleura. To date, in the pancreas, only 14 cases have been reported in the English literature. CASE REPORT: A 52-year-old male was diagnosed incidentally with a suspected neuroendocrine tumor (NET) of the pancreas. He underwent pancreatic enucleation of the mass, which, at final pathology, showed spindle cell proliferation set in a collagenous background and featuring the presence of hemangiopericytoma-like blood. Immunohistochemistry showed cytoplasmic expression of CD34 and nuclear expression of STAT6. As mitotic activity was of 1 mitoses/10 high-power fields (HPFs) a diagnosis of conventional SFT was made. The patient was discharged without major complications and is alive and free of disease after 24 months. CONCLUSION: SFTs of pancreas are rare tumors, often mimicking pancreatic NET.

Totally Laparoscopic Microwave Ablation and Portal Vein Ligation for Staged Hepatectomy : A New Minimally Invasive Two-Stage Hepatectomy.

BACKGROUND: Laparoscopic microwave ablation and portal vein ligation for staged hepatectomy (LAPS) is a new technique with a first laparoscopic step available in cases of unresectable right liver masses and inadequate future liver remnant (FLR). METHODS: In Step 1, laparoscopic right portal vein occlusion is performed with microwave ablation on the future transection plane and in the FLR. Step 2 consists of a totally laparoscopic right trisectionectomy. RESULTS: Duration of the Step 1 operation was 170 min, without the need for blood transfusions and intensive care unit admission. The postoperative liver volumetric computed tomography scan was performed on postoperative day 9 and revealed a satisfactory left hepatic hypertrophy (FLR 666 cm(3); FLR to body weight ratio 0.96; FLR increase 90.4 %; daily FLR hypertrophy 35 cm(3)/day). Duration of the Step 2 operation was 630 min (liver transection time 240 min). Blood loss was 700 cc, with no need for transfusion. The specimen was extracted through a 10-cm Pfannenstiel incision, and pathology revealed a tumor-free resection margin (R0). The patient was discharged on postoperative day 7 without complications (total hospital stay for Step 1 + Step 2: 10 days). CONCLUSIONS: Totally LAPS is a technically feasible and safe procedure. It could provide benefit in selected patients with primarily non-resectable liver cancer, making extreme liver surgery easy and safe in well-selected patients.

Totally laparoscopic caudate lobe resection: technical aspects and literature review.

The particular anatomic location of the hepatic caudate lobe between the hilar plate and inferior vena cava means that it is still considered unsuitable for laparoscopic measures and a difficult site even for conventional surgery. Here we describe the first case to be reported in the literature of caudate lobe resection for a single metastasis from breast adenocarcinoma that was completed using an exclusively laparoscopic procedure and a simplified scheme involving the placement of 4 trocars, without any need for conversion or the Pringle maneuver. The patient was 31 years old with a history of radical right mastectomy and chemotherapy. The patient's postoperative course was uneventful and she was discharged 4 days after the surgery. Twelve months on, she is currently alive and disease free.

Vascular inflow control during hemi-hepatectomy: a comparison between intrahepatic pedicle ligation and extrahepatic vascular ligation.

BACKGROUND: Intrahepatic pedicle ligation (IPL) is an alternative to extrahepatic portal dissection (EPD). Although IPL has been well described, concern has arisen over a possible association with increased complication rates. METHODS: Patients who underwent hemi-hepatectomy during January 1995 to December 2010 were reviewed and the inflow control technique (IPL versus EPD) documented. Patient, tumour, treatment and outcome variables were compared. RESULTS: A total of 798 patients underwent hemi-hepatectomy, 568 (71.2%) of the right and 230 (28.8%) of the left liver. In univariate analysis, factors associated with the choice of IPL included surgeon, right hepatectomy, preoperative portal vein embolization, diagnosis of colorectal cancer liver metastasis, and smaller tumour size (P < 0.011). In multivariate analysis, right hepatectomy [versus left: hazard ratio (HR) 3.878, 95% confidence interval (CI) 1.15-13.14; P = 0.029] and smaller tumour size (median of 4.5 cm versus 5.5 cm: HR 0.72, 95% CI 0.59-0.88; P = 0.002) were associated with IPL. Pringle manoeuvre time was longer in IPL procedures (40 min versus 29 min; P < 0.001). Complication rates (49.8% in IPL versus 48.4% in EPD; P = 0.706) were similar in both groups, as was the severity of complications; 17.6% of EPD and 22.3% of IPL patients experienced complications of grade ≥3 (P = 0.225). CONCLUSIONS: Patients with small tumours undergoing right hepatectomy were more likely to undergo IPL. In selected patients, IPL was not associated with an increased complication rate and thus it should be considered a safe approach.

Clear cell sarcoma of the ileum: report of a case and review of the literature.

INTRODUCTION: Clear cell sarcoma of the gastrointestinal tract (CCS-GI) is an extremely rare and aggressive tumor, which often mimics other neoplastic processes. Because of this feature, its real incidence may have been underestimated, especially in the past when genetic tests were less available than nowadays. To date, less then 30 cases have been described in the literature on the GI tract. CASE PRESENTATION: We report the case of a 69-year-old woman who presented with active rectal bleeding. After a negative colonoscopy, the patient underwent a video-capsule endoscopy. The latter detected an ileal mass that was surgically resected. The microscopic appearance was consistent with a malignant mesenchymal neoplasm; immunohistochemistry was positive for S100 protein, CD56, and INI1. Fluorescence in situ hybridization showed a translocation involving the EWSR1 (Ewing sarcoma 1) gene region. All these findings were consistent with a CCS-GI. CONCLUSION: Herein we present a case of CCS-GI, discuss its clinical and pathological features, and review the literature on the subject.

Clinical presentation and diagnosis of intestinal adenocarcinoma in Crohn's disease: analysis of clinical predictors and of the life-time risk.

BACKGROUND: Late diagnosis of cancer in CD often occurs, and the prognosis is poor. The primary aim of this study was to assess the relationship between clinical presentation and diagnosis of intestinal adenocarcinoma in CD; the secondary aim was to evaluate the timing of cancer occurrence in CD patients. PATIENTS AND METHODS: Medical records of 12 consecutive patients with intestinal adenocarcinoma in CD and of 79 consecutive CD patients undergoing bowel surgery were reviewed. Presentation symptoms were analyzed as possible predictors. Timing of intestinal adenocarcinoma occurrence in patients with CD was analyzed including all the 347 consecutive patients that had undergone surgery for CD in our institute from January 1984 to June 2008. Life table analysis and uni/multivariate analyses were performed. RESULTS: Ten men and two women underwent surgery for intestinal cancer in CD with a median age of 50 years (31-68). Carcinomas were localized in the terminal ileum in four cases, right colon in three, transverse colon in one, sigmoid colon in one, rectum in two, and an anorectal fistula in one. Only three patients were pre-operatively diagnosed with cancer. At multivariate analysis only age (OR 1.057 (95% CI 0.999-1.107), p = 0.05) and obstruction (OR 6.530 (95% CI 1.533-27.806), p = 0.01) significantly predicted cancer diagnosis. The risk rate (RR) for cancer occurrence started to rise at the end of the third decade of life (RR = 0.005). The analysis of risk rate for cancer occurrence during overt CD showed that it is initially high at onset (RR = 0.001) and after two other peaks at 150 months from onset, it began to rise again. The presence of Crohn's colitis was associated to a significant risk of cancer (HR = 4.790, p = 0.009) while the use of 5-ASA resulted to be a protective factor against cancer occurrence (HR = 0.122, p = 0.013). DISCUSSION: In CD, rectal bleeding, the most common alarm symptom for intestinal cancer, is not useful for an early diagnosis. CD patients presenting with an older age and obstruction should be thoroughly investigated to rule out neoplastic lesions. There is probably no safe interval of CD where surveillance for intestinal cancer can be omitted. In the meantime, even in absence of active disease, all CD patients should undergo therapy with 5-ASA.

Lyn-mediated mitochondrial tyrosine phosphorylation is required to preserve mitochondrial integrity in early liver regeneration.

Functional alterations in mitochondria such as overproduction of ROS (reactive oxygen species) and overloading of calcium, with subsequent change in the membrane potential, are traditionally regarded as pro-apoptotic conditions. Although such events occur in the early phases of LR (liver regeneration) after two-thirds PH (partial hepatectomy), hepatocytes do not undergo apoptosis but continue to proliferate until the mass of the liver is restored. The aim of the present study was to establish whether tyrosine phosphorylation, an emerging mechanism of regulation of mitochondrial function, participates in the response to liver injury following PH and is involved in contrasting mitochondrial pro-apoptotic signalling. Mitochondrial tyrosine phosphorylation, negligible in the quiescent liver, was detected in the early phases of LR with a trend similar to the events heralding mitochondrial apoptosis and was attributed to the tyrosine kinase Lyn, a member of the Src family. Lyn was shown to accumulate in an active form in the mitochondrial intermembrane space, where it was found to be associated with a multiprotein complex. Our results highlight a role for tyrosine phosphorylation in accompanying, and ultimately counteracting, mitochondrial events otherwise leading to apoptosis, hence conveying information required to preserve the mitochondrial integrity during LR.