Correlation Between Indocyanine Green Fluorescence Patterns and Grade of Differentiation of Hepatocellular Carcinoma: A Western Prospective Cohort Study.

Background. Most of the available evidence on the use of indocyanine green (ICG) fluorescence in clinical practice consists of articles published by surgeons of the Asian-Pacific area. We performed a prospective cohort study to assess the patterns of ICG fluorescence in Western hepatocellular carcinoma (HCC) counterparts.Methods. From April 2019 to January 2022, a total of 31 consecutive patients who underwent laparoscopic liver resection (LLR) for superficial HCC were enrolled in this prospective study. All patients underwent laparoscopic staging with both laparoscopic ultrasound (LUS) and ICG fluorescence imaging.Results. A total of 38 hepatocellular carcinomas (HCCs) were enrolled: 23 superficial (surfacing at the liver's Glissonian capsule), 5 exophytic, 5 shallow (<8 mm from the hepatic surface) and 5 deep (>10 mm from the hepatic surface). The detection rate with preoperative imaging (abdominal CT/MRI), LUS, ICG fluorescence and combined modalities (ICG and LUS) was 97.4%, 94.9%, 89.7% and 100%, respectively. The five deep seated lesions underwent ultrasound-guided laparoscopic thermal ablation. The other 33 HCCs were treated with minimally invasive liver resection. Intraoperative ultrasound patterns were registered for each single nodule resected. The ICG fluorescence pattern was classified in two types: total fluorescence (all the tumoral tissue showed strong and homogeneous fluorescence), n = 9/33 (27.3%), and non-total fluorescence (partial and rim fluorescence), n = 24/33 (72.7%). There was a statistical correlation between ICG patterns and grade of differentiation. Almost all lesions with uniform fluorescence pattern were well-differentiated HCCs (G1-G2), while partial and rim-type fluorescence pattern were more common among moderately and poorly differentiated HCCs (G3-G4) (88.9% vs 11.1%, 37.5% vs 62.5%, P = .025, respectively).Conclusions. ICG fluorescence imaging could be used to identify early the grade of HCC, ie intraoperatively, thus influencing the intraoperative treatment.

Short and long-term outcomes after minimally invasive liver resection for single small hepatocellular carcinoma: An analysis of 714 patients from the IGoMILS (Italian group of minimally invasive liver surgery) registry.

BACKGROUND: Widespread use of minimally invasive liver surgery (MILS) contributed to the reduction of surgical risk of liver resection for hepatocellular carcinoma (HCC). Aim of this study was to analyze outcomes of MILS for single ≤3 cm HCC. METHODS: Patients who underwent MILS for single ≤3 cm HCC (November 2014 - December 2019) were identified from the Italian Group of Minimally Invasive Liver Surgery (IGoMILS) Registry. RESULTS: Of 714 patients included, 641 (93.0%) were Child-Pugh A; 65.7% were limited resections and 2.2% major resections, with a conversion rate of 5.2%. Ninety-day mortality rate was 0.3%. Overall morbidity rate was 22.4% (3.8% major complications). Mean postoperative stay was 5 days. Robotic resection showed longer operative time (p = 0.004) and a higher overall morbidity rate (p < 0.001), with similar major complications (p = 0.431). Child-Pugh B patients showed worse mortality (p = 0.017) and overall morbidity (p = 0.021), and longer postoperative stay (p = 0.005). Five-year overall survival was 79.5%; cirrhosis, satellite micronodules, and microvascular invasion were independently associated with survival. CONCLUSIONS: MILS for ≤3 cm HCC was associated with low morbidity and mortality rates, showing high safety, and supporting the increasing indications for surgical resection in these patients.

COVID-19 outbreak and acute cholecystitis in a Hub Hospital in Milan: wider indications for percutaneous cholecystostomy.

BACKGROUND: COVID-19 pandemic has impacted the Italian National Health Care system at many different levels, causing a complete reorganization of surgical wards. In this context, our study retrospectively analysed the management strategy for patients with acute cholecystitis. METHODS: We analysed all patients admitted to our Emergency Department for acute cholecystitis between February and April 2020 and we graded each case according to 2018 Tokyo Guidelines. All patients were tested for positivity to SARS-CoV-2 and received an initial conservative treatment. We focused on patients submitted to cholecystostomy during the acute phase of pandemic and their subsequent disease evolution. RESULTS: Thirty-seven patients were admitted for acute cholecystitis (13 grade I, 16 grade II, 8 grade III). According to Tokyo Guidelines (2018), patients were successfully treated with antibiotic only, bedside percutaneous transhepatic gallbladder drainage (PC) and laparoscopic cholecystectomy (LC) in 29.7%, 21.6% and 48.7% of cases respectively. Therapeutic strategy of three out of 8 cases, otherwise fit for surgery, submitted to bedside percutaneous transhepatic gallbladder drainage (37.5%), were directly modified by COVID-19 pandemic: one due to the SARS-CoV-2 positivity, while two others due to unavailability of operating room and intensive care unit for post-operative monitoring respectively. Overall success rate of percutaneous cholecystostomy was of 87.5%. The mean post-procedural hospitalization length was 9 days, and no related adverse events were observed apart from transient parietal bleeding, conservatively treated. Once discharged, two patients required readmission because of acute biliary symptoms. Median time of drainage removal was 43 days and only 50% patients thereafter underwent cholecystectomy. CONCLUSIONS: Percutaneous cholecystostomy has shown to be an effective and safe treatment thus acquiring an increased relevance in the first phase of the pandemic. Nowadays, considering we are forced to live with the SARS-CoV-2 virus, PC should be considered as a virtuous, alternative tool for potentially all COVID-19 positive patients and selectively for negative cases unresponsive to conservative therapy and unfit for surgery.

LI-RADS to categorize liver nodules in patients at risk of HCC: tool or a gadget in daily practice?

PURPOSE: To determine the effectiveness of liver reporting and data system (LI-RADS) to diagnose hepatocellular carcinoma (HCC) and to retrospectively evaluate its impact on the adopted therapeutic strategy. MATERIALS AND METHODS: Preoperative imaging of 40 of 350 patients (median age 66, 31 M/9 F) submitted to liver resection for suspected HCC, between January 2008 and August 2019, has been retrospectively analyzed by two radiologists with different expertise, according to CT/MRI LI-RADS® v2018, both blinded to clinical and pathological results and untrained to using aforementioned scoring system. RESULTS: The perfect agreement between the readers was about 62.5% (25/40) (Cohen k: 0.41), better for LR-5 category (16/25) and higher in magnetic resonance imaging (MRI) investigations (68%; 13/19), which has been demonstrated the modality of choice for diagnosis of high probable and certain HCC, with arterial phase hyperenhancement as the most sensitive and accurate major feature. Compared to final histology, LR4 and LR5 scores assigned by senior radiologist reached sensitivity, specificity, positive and negative predictive values (PPV, PNV) and diagnostic accuracy of 90,9%, 29,0%, 93,8%, 62,5% and 87,5%, respectively, slightly higher than junior's ones. Misdiagnosis of HCC was done by both radiologists in the same two patients: 1 primary hepatic lymphoma (PHL) and 1 regenerative liver nodule (RLN). If LI-RADS would have been applied at the time of pre-surgical imaging, treatment planning would be modified in 10% of patients (4/40); the patient scheduled as LR-3 and finally resulted a focal nodular hyperplasia would have avoided liver resection. CONCLUSIONS: Application of LI-RADS, especially on MRI, may provide a more accurate evaluation of suspected HCC. PHL and RLN are the Achille's heels according to our experience.

Deficient Natural Killer Cell NKp30-Mediated Function and Altered NCR3 Splice Variants in Hepatocellular Carcinoma.

The activating natural cytotoxicity receptor NKp30 is critical for natural killer (NK) cell function and tumor immune surveillance. The natural cytotoxicity receptor-3 (NCR3) gene is transcribed into several splice variants whose physiological relevance is still incompletely understood. In this study, we investigated the role of NKp30 and its major ligand B7 homolog 6 (B7-H6) in patients with hepatocellular carcinoma (HCC). Peripheral blood NK cell phenotype was skewed toward a defective/exhausted immune profile with decreased frequencies of cells expressing NKp30 and natural killer group 2, member D and an increased proportion of cells expressing T-cell immunoglobulin and mucin-domain containing-3. Moreover, NKp30-positive NK cells had a reduced expression of NCR3 immunostimulatory splice variants and an increased expression of the inhibitory variant in patients with advanced tumor, resulting in deficient NKp30-mediated functionality. Tumor-infiltrating lymphocytes showed a prevalent inhibitory NKp30 isoform profile, consistent with decreased NKp30-mediated function. Of note, there were significant differences in the cytokine milieu between the neoplastic and the surrounding non-neoplastic tissue, which may have further influenced NKp30 function. Exposure of NK cells to B7-H6-expressing HCC cells significantly down-modulated NKp30, that was prevented by small interfering RNA-mediated knockdown, suggesting a role for this ligand in inhibiting NKp30-mediated responses. Interestingly, B7-H6 expression was reduced in HCC tissue and simultaneously augmented as a soluble form in HCC patients, particularly those with advanced staging or larger nodule size. Conclusion: These findings provide evidence in support of a role of NKp30 and its major ligand in HCC development and evolution.

Intraoperative ultrasound for prediction of hepatocellular carcinoma biological behaviour: Prospective comparison with pathology.

BACKGROUND & AIMS: Preoperative prediction of both microinvasive hepatocellular carcinoma and histological grade of hepatocellular carcinoma is pivotal to treatment planning and prognostication. The aim of this study was to evaluate whether some intraoperative ultrasound features correlate with both the presence of same histological patterns and differentiation grade of hepatocellular carcinoma on the histological features of the primary resected tumour. METHODS: All patients with single, small hepatocellular carcinoma that underwent hepatic resection were included in this prospective double-blind study: the intraoperative ultrasound patterns of nodule were registered and compared with similar histological features. RESULTS: A total of 179 patients were enclosed in this study: 97 (54%) patients (34% in HCC ≤2 cm) had a microinvasive hepatocellular carcinoma at ultrasound examination, while 82 (46%) patients (41% in HCC ≤2 cm) at histological evaluation. Statistical analysis showed that diameters ≤2 cm, presence of satellites and microinvasive hepatocellular carcinoma at ultrasound examination were the variables with the strongest association with the histological findings. In the multivariate analysis, the vascular microinfiltration and infiltrative hepatocellular carcinoma aspect were independent predictors for grading. CONCLUSIONS: In patients with cirrhosis and hepatocellular carcinoma, the prevalence of microinvasive hepatocellular carcinoma is high, even in cases of HCC ≤2 cm. Intraoperative ultrasound findings strongly correlated with histopathological criteria in detecting microinvasive patterns and are useful to predict neoplastic differentiation. The knowledge of these features prior to treatment are highly desired (this can be obtained by an intraoperative ultrasound examination), as they could help in providing optimal management of patients with hepatocellular carcinoma.

Comparison of Laparoscopic Microwave to Radiofrequency Ablation of Small Hepatocellular Carcinoma (≤3 cm).

BACKGROUND: Laparoscopic thermal ablation is a common alternative to surgical resection in treating hepatic tumors, particularly in those located in difficult-to-reach locations. OBJECTIVE: The aim of this study was to compare the safety and long-term efficacy of laparoscopic radiofrequency ablation (RFA) and microwave ablation (MWA) in treating hepatocellular carcinoma (HCC). METHOD: From February 2009 to May 2015, data from patients with HCC nodules who had undergone either laparoscopic MWA or laparoscopic RFA were examined. Complications, complete ablation rates, local tumor progression (LTP) rates, and disease-free and cumulative survival rates were compared between the two treatment groups. RESULTS: A total of 154 patients with HCC (60 MWA and 94 RFA) were treated via the laparoscopic approach. Major complication rates were identified as 1 and 2 % in the RFA and MWA groups, respectively (p = 0.747). Complete ablation rates were 95 % for both treatment groups (p = 0.931), and LTP rates were 21.2 % for RFA and 8.3 % for MWA (p = 0.034). Disease-free survival rates at 5 years were 19 % in the RFA group and 12 % in the MWA group (p = 0.434), while cumulative survival rates at 5 years were 50 % in the RFA group and 37 % in the MWA group (p = 0.185). CONCLUSION: Laparoscopic RFA and MWA appear to be safe in the treatment of early-stage HCC. The LTP rates were lower in the laparoscopic MWA group compared with the laparoscopic RFA group, but their respective overall and disease-free survival rates remained similar.

Long-term outcome of laparoscopic ablation therapies for unresectable hepatocellular carcinoma: a single European center experience of 426 patients.

BACKGROUND: Radiofrequency ablation (RFA) is widely used as a first-line option in patients with hepatocellular carcinoma (HCC). However, since percutaneous approach of RFA may be, in some cases, unfeasible by the tumor size and its location, laparoscopic ablation therapies (LATs) were used as an alternative. Objective of the present study was to assess the efficacy of laparoscopic ultrasound examination in addition to LATs in the treatment of HCC in patients not eligible for percutaneous RFA or surgical resection. METHODS: Four hundred and twenty-six patients who underwent LATs were analyzed. Laparoscopic approach was offered to patients fulfilling at least one of the following criteria: (a) patients with a single nodule or up to three nodules smaller than 3 cm not suitable for liver transplantation or not eligible for HR because of severe portal hypertension, impaired liver function, or coexistent comorbidities; (b) patients not suitable for percutaneous RFA because of inconvenient tumor location; and (c) short-term recurrence of HCC (<3 months). RESULTS: Technical success was achieved in one session in 396 patients (93 %). One-month mortality and morbidity rates were 0.23 % (1 patient) and 25 % (106 patients), respectively. During a median follow-up of 37.2 months (range 2-193) in the remaining 425 patients, 276 (65 %) developed intra-hepatic recurrence: It appeared as a local tumor progression in 65 cases (15 %). Patients median survival was 39 months (95 % CI 34.8-47.2), while overall survivals at 1, 3, and 5 years were 88, 55, and 34 %, respectively. CONCLUSIONS: In the treatment of HCC, LATs proved to be a safe and effective technique, as they permit to treat with low-morbidity-rate lesions not manageable by percutaneous approach. Moreover, they allow achieving a more accurate staging of the disease in one-fifth of patients, thus better redefining the prognosis of such individuals.

Hepatic resection for hepatocellular carcinoma in patients with Child-Pugh's A cirrhosis: is clinical evidence of portal hypertension a contraindication?

BACKGROUND: According to international guidelines [European Association for the Study of the Liver (EASL) and the American Association for the Study of Liver Diseases (AASLD)], portal hypertension (PHTN) is considered a contraindication for liver resection for hepatocellular carcinoma (HCC), and patients should be referred for other treatments. However, this statement remains controversial. The aim of this study was to elucidate surgical outcomes of minor hepatectomies in patients with PHTN (defined by the presence of esophageal varices or a platelet count of <100,000 in association with splenomegaly) and well-compensated liver disease. METHODS: Between 1997 and 2012, a total of 223 cirrhotic patients [stage A according to the Barcelona Clinic Liver Cancer (BCLC) classification] were eligible for this analysis and were divided into two groups according to the presence (n = 63) or absence (n = 160) of PHTN. The demographic data were comparable in the two patient groups. RESULTS: Operative mortality was not different (only one patient died in the PHTN group). However, patients with PHTN had higher liver-related morbidity (29% versus 14%; P = 0.009), without differences in hospital stay (8.8 versus 9.8 days, respectively). The PHTN group showed a worse survival rate only if biochemical signs of liver decompensation existed. Multivariate analysis identified albumin levels as an independent predictive factor for survival. CONCLUSIONS: PHTN should not be considered an absolute contraindication to a hepatectomy in cirrhotic patients. Patients with PHTN have short- and long-term results similar to patients with normal portal pressure. A limited hepatic resection for early-stage tumours is an option for Child-Pugh class A5 patients with PHTN.

Laparoscopic Microwave Ablation: Which Technologies Improve the Results.

Liver resection is the best treatment for hepatocellular carcinoma (HCC) when resectable. Unfortunately, many patients with HCC cannot undergo liver resection. Percutaneous thermoablation represents a valid alternative for inoperable neoplasms and for small HCCs, but it is not always possible to accomplish it. In cases where the percutaneous approach is not feasible (not a visible lesion or in hazardous locations), laparoscopic thermoablation may be indicated. HCC diagnosis is commonly obtained from imaging modalities, such as CT and MRI, However, the interpretation of radiological images, which have a two-dimensional appearance, during the surgical procedure and in particular during laparoscopy, can be very difficult in many cases for the surgeon who has to treat the tumor in a three-dimensional environment. In recent years, more technologies have helped surgeons to improve the results after ablative treatments. The three-dimensional reconstruction of the radiological images has allowed the surgeon to assess the exact position of the tumor both before the surgery (virtual reality) and during the surgery with immersive techniques (augmented reality). Furthermore, indocyanine green (ICG) fluorescence imaging seems to be a valid tool to enhance the precision of laparoscopic thermoablation. Finally, the association with laparoscopic ultrasound with contrast media could improve the localization and characteristics of tumor lesions. This article describes the use of hepatic three-dimensional modeling, ICG fluorescence imaging and laparoscopic ultrasound examination, convenient for improving the preoperative surgical preparation for personalized laparoscopic approach.

Laparoscopic Indocyanine Green Fluorescence Imaging for Intrahepatic Cholangiocarcinoma.

BACKGROUND: Indocyanine green fluorescence (ICG) is one of the first fluorophore that found a clinical application in medicine. In the liver, ICG fluorescence is due to the preserved uptake but impaired washout of the dye from hepatocellular cells into the bile ducts. Therefore, some hepatobiliary surgeons proposed the technique of intravenous ICG injection before surgery for the detection of superficial hepatocarcinomas (HCCs) and colorectal liver metastases (CRLMs). Little evidence exists regarding the use of ICG to identify other hepatic tumors, such as intrahepatic cholangiocarcinoma (ICC). We report two patients affected by ICC who underwent laparoscopic liver resection with lymphadenectomy, the ICG staining was routinely performed not only to evaluate the site of the hepatic lesions but also to guide the extension of liver resection. METHODS: It was injected intravenously a single dose of ICG dye (0.5 mg/kg) during liver function tests 5 days before scheduled surgery. All patients underwent laparoscopic staging with both laparoscopic ultrasound and ICG fluorescence imaging. RESULTS: It was identified two different patter of ICG imaging: rim and segmental fluorescence for mass forming and mixed ICC subtype respectively. CONCLUSIONS: Identification of the ICC subtype before definitive histological examination may have an impact on the surgical plan.

Hepatic resection for "BCLC stage A" hepatocellular carcinoma. The prognostic role of alpha-fetoprotein.

BACKGROUND: Our aim was to assess the capability of Barcelona Clinic Liver Cancer (BCLC) staging system in allocating stage A patients to hepatic resection (HR) and the effect on survival. METHODS: We enrolled 132 patients with hepatocellular carcinoma (HCC) amenable to HR. All patients underwent ultrasound (US)-guided anatomical resection (≤2 segments) and then postoperative results were evaluated. RESULTS: Results showed 95% of patients were Child A, 49% in BCLC A1, 21% in A2, 6% in A3, and 24% in A4. No 30-day mortality occurred. Overall survival got worse from A1 to A4 (P = 0.0271), while no differences were found in Childs A patients with or without portal hypertension (P = 0.1674). Multivariate analysis (Cox model) shows that only AFP (<20 ng/ml) was an independent predictor of survival: If the AFP is incorporated in BCLC staging system (all A1 and A2 patients with abnormal AFP levels were included in A3 subgroup), 5-year survival rate including normal AFP for A1 was 57% and for A2 was 65%, whereas the survival rates impaired in the worst candidates (5-year survival rate including AFP abnormal for A3 and A4 was 36%; P = 0.002). So, introducing AFP in BCLC classification it is possible to simplify the algorithm in only 2 classes, well-separated in survival curves (class 1 [AFP-]: 60%; class 2 [AFP+]: 37%; P = 0.0001). CONCLUSION: Our experience stressed the high value of BCLC system in staging of patients with HCC, but underlined that in selected patients (normal AFP) even A2 group may benefit from HR with a good survival.

MicroRNA profiling of hepatocarcinogenesis identifies C19MC cluster as a novel prognostic biomarker in hepatocellular carcinoma.

BACKGROUND AND AIMS: Progressive hepatocarcinogenesis is a stepwise process that drives liver transformation. However, the molecular mechanisms of early liver transformation are far from clear. A role for microRNAs (miRNA) as diagnostic and prognostic factors in human tumours, including hepatocellular carcinoma (HCC), is promising. We aimed to identify novel miRNA as biomarkers for differential diagnosis and predictors of disease progression. METHODS: We used a low-density array platform to profile the expression of 664 mature miRNA in a cohort of 60 hepatitis C virus-positive liver lesions representative of all stages of progressive hepatocarcinogenesis. We validated selected miRNA in two independent patient series by qPCR and we characterized the genomic status of the miRNA cluster C19MC by fluorescent in situ hybridization and copy-number variation analyses. RESULTS: A 18-miRNA signature distinguished cirrhosis, dysplastic nodules and HCC lesions. Four miRNAs overexpressed in HCCs belonged to chromosome 19 miRNA cluster (C19MC). Significant overexpression of C19MC in early HCC compared to dysplastic nodules could be confirmed in a second series of hepatitis B virus-related liver lesions (n = 30). In a third series of 61 HCCs, C19MC cluster was overexpressed in HCCs compared to matched cirrhotic parenchyma and regardless of the type of viral infection. High C19MC miRNA levels were correlated with poor clinico-pathological features, increased risk of tumour recurrence and shorter overall survival time. HCCs overexpressing the C19MC cluster showed genetic amplification of the corresponding locus. CONCLUSIONS: C19MC cluster is a novel molecular alteration characteristic of liver cancer and predictor of poor prognosis. C19MC is an attractive candidate for novel HCC therapies.

Recurrent hepatocellular carcinoma successfully treated with laparoscopic thermal ablation.

BACKGROUND: Aggressive treatment of intrahepatic recurrence of hepatocellular carcinoma (HCC) increases patients' survival. This study aimed to evaluate laparoscopic thermal ablation (TA) in the treatment of intrahepatic HCC recurrences. METHODS: A retrospective analysis was performed on 88 patients (REC group) who underwent laparoscopic TA after prior TA (66 patients.) or partial hepatic resection (HR) (22 patients) as initial local treatment. Another 170 patients with primary HCC tumors (PRIM group) were regarded as the control group. RESULTS: The postoperative morbidity rates were similar for the patients with prior TA (18%) and those with prior HR (21%) (nonsignificant difference [NS]). The overall survival rates were not significantly different between the two groups (3-year survival rates of 59 and 78%, respectively; P = 0.1662). Moreover, the disease-free survival (DFS) rates did not differ significantly between the patients with prior TA and those with prior HR (3-year DFS of 21 and 8%, respectively; P = 0.1911). The incidences of morbidity in the whole REC (21%) and PRIM (20%) groups were similar (P = NS), and no mortality occurred in either group (0%). The cumulative 3-year survival rate was 63% in the REC group and 59% in the PRIM group (P = 0.5739), whereas the 3-year DFS rate was 17% in the REC group and 22% in the PRIM group (P = 0.5266). CONCLUSION: Laparoscopic TA can be performed safely and may be effective for intrahepatic HCC recurrence after prior TA or HR. It leads to survival and DFS rates similar to those obtained using laparoscopic TA for primary HCC without increasing morbidity. Laparoscopic TA could be proposed as first-line treatment of intrahepatic HCC recurrence for selected patients.

Role of Indocyanine Green Fluorescence Imaging in Minimally Invasive Resection of Colorectal Liver Metastases.

Indocyanine green (ICG) fluorescence imaging is an easy and reproducible method to detect hepatic lesions, both primary and metastatic. This review reports the potential benefits of this technique as a tactile mimicking visual tool and a navigator guide in minimally invasive liver resection of colorectal liver metastases (CRLM). PubMed and MEDLINE databases were searched for studies reporting the use of intravenous injection of ICG before minimally invasive surgery for CLRM. The search was performed for publications reported from the first study in 2014 to April 2021. The final review included 13 articles: 6 prospective cohort studies, 1 retrospective cohort study, 3 case series, 1 case report, 1 case-matched study, and 1 clinical trial registry. The administered dose ranged between 0.3 and 0.5 mg/kg, while timing ranged between 1 and 14 days before surgery. CRLM detection rate ranged between 30.3% and 100% with preoperative imaging (abdominal computed tomography/magnetic resonance imaging), between 93.3 and 100% with laparoscopic ultrasound, between 57.6% and 100% with ICG fluorescence, and was 100% with combined modalities (ICG and laparoscopic ultrasound) with weighted averages of 77.42%, 95.97%, 79.03%, and 100%, respectively. ICG fusion imaging also allowed to detect occult small-sized lesions, not diagnosed preoperatively. In addition, ICG is effective in real-time assessment of surgical margins by evaluating the integrity of the fluorescent rim around the CRLM.

Impact of Platelet Count on Perioperative Bleeding in Patients With Cirrhosis Undergoing Surgical Treatments of Liver Cancer.

In patients with cirrhosis with severe thrombocytopenia (platelet count [PC] <50 × 109 /L) and undergoing invasive procedures, it is common clinical practice to increase the PC with platelet transfusions or thrombopoietin receptor agonists to reduce the risk of major periprocedural bleeding. The aim of our study was to investigate the association between native PC and perioperative bleeding in patients with cirrhosis undergoing surgical procedures for the treatment of hepatocellular carcinoma (HCC). We retrospectively evaluated 996 patients with cirrhosis between 1996 and 2018 who underwent surgical treatments of HCC by liver resection (LR) or radiofrequency ablation (RFA) without prophylactic platelet transfusions. Patients were allocated to the following three groups based on PC: high (>100 × 109 /L), intermediate (51-100 × 109 /L), and low (≤50 × 109 /L). PC was also analyzed as a continuous covariate on multivariable analysis. The primary endpoint was major perioperative bleeding. The overall event rate of major perioperative bleeding was 8.9% and was not found to differ significantly between the high, intermediate, and low platelet groups (8.1% vs. 10.2% vs. 10.8%, P = 0.48). On multivariable analysis, greater age, aspartate aminotransferase, lower hemoglobin, and treatment with LR (vs. RFA) were found to be significant independent predictors of major perioperative bleeding, with associations with disease etiology and year of surgery also observed. After adjusting for these factors, the association between PC and major perioperative bleeding remained nonsignificant. Conclusion: Major perioperative bleeding was not significantly associated with PC in patients with cirrhosis undergoing surgical treatment of HCC, even when their PC was <50 × 109 /L. With the limit of a retrospective analysis, our data do not support the recommendation of increasing PC in patients with severe thrombocytopenia in order to decrease their perioperative bleeding risk.

Is there still a role for laparoscopy combined with laparoscopic ultrasonography in the staging of pancreatic cancer?

PURPOSE: This study was designed to compare our laparoscopic ultrasonography (LUS) experience in the resectability evaluation of pancreatic or periampullary cancers (PAC) in two different periods: before and after the introduction of multidetector CT (MDCT). METHODS: We prospectively enrolled 104 CT-resectable patients with PAC. During Step 1 (1995-1999), we performed LUS on all patients, whereas during Step 2 (2002-2007), LUS was performed selectively according to Pisters' criteria. RESULTS: LUS was satisfactorily performed in all cases. At Step 1 accuracy of LUS in predicting pancreatic resectability was high (96%) but it was markedly lower in a subgroup of patients with close contact between tumor and portal vein (sensibility of 57%). At Step 2, selective LUS was performed on 9 of 64 patients (14%). LUS confirmed the MDCT finding of unresectability in 8 of 9 cases, and allowed curative resection in 1 case. Only 1 of 55 of the patients who did not undergo LUS would have benefited from the procedure. The yield of LUS decreased from 45% before to 1.8% after MDCT. CONCLUSIONS: In resectable-MDCT patients, routine LUS is unjustified. However, in doubtful MDCT cases, LUS has yet a good yield. In the event of close vascular contact, neither MDCT nor LUS seem to be conclusive, and laparotomy is still the only solution.

Fluorescence and Ultrasound-guided Laparoscopic Resection of Caudate Lobe for Hepatocellular Carcinoma Located in the Retrocaval Portion.

BACKGROUND: Contrast-enhanced intraoperative ultrasonography (CEIOUS) and indocyanine green fluorescence were interesting tool for the visualization of intrahepatic neoplastic nodules. The combinations of the 2 technologies could increase tumor detection and the radicality of resection, allowing the use of a pure laparoscopic approach. METHODS: The patient was an 81-year-old man with a history of hypertension and treated hepatitis C infection, with a sustained serological response from 2018, previously undergoing laparotomic resection for hepatocellular carcinoma (HCC) in segment 8.During his regular hepatological follow-up, a 25 mm nodule was detected in segment 1, in a retrocaval position. Considering clinical presentation, good liver function (Child A5-MELD 8) and imaging, pure laparoscopic resection of the caudate lobe was performed using fluorescence imaging and CEIOUS navigation guidance. RESULTS: The operation last for 205 minutes. Blood loss was 100 mL and no blood transfusion was required. She resumed diet on the next day and was discharged 4 days after the operation. Histopathologic examination showed 27 mm HCC with a clear margin. Contrast computed tomography scan performed 3 months after the operation showed no recurrence of the disease. CONCLUSIONS: A laparoscopic isolated caudate resection for HCC located in the retrocaval portion of the cirrhotic liver seems to be feasible in selected patients and fluorescence imaging and CEIOUS navigation guidance could guarantee a safe and successful surgery.

Guidelines Adaptation to the COVID-19 Outbreak for the Management of Hepatocellular Carcinoma.

Background: COVID-19 pandemic rendered the surgical approach as well as the surgical indication very complex due to the outstanding consumption of public health system' resources, especially in the intensive care subdivision. A multidisciplinary team-based strategy is necessary to adapt guidelines and medical practices to the actual situation. The aim of this study is to evaluate the changes in the therapeutic algorithm in a small group of patients with hepatocellular carcinoma (HCC) enlisted for surgery during the COVID-19 outbreak. Materials and Methods: A multidisciplinary strategy has been adopted to allocate HCC patients to a treatment that permitted to reduce the risk of complications and the hospital stay, thus preventing contamination by the virus. Nasopharyngeal swab and a chest radiograph were performed in all patients within 48 hours before the surgical procedure: in the suspected cases with negative COVID tests, we prudently postponed surgery and repeated the diagnostic tests after 15 days. Results: During the emergency state, 11 HCC patients were treated (8 laparoscopic ablations and 3 hepatic resections). We reported only 1 postoperative complication (hemothorax) and 1 death during the follow-up for COVID pneumonia. Comparing our performances with those in the same time frame in the past 4 years, we treated a similar number of HCC patients, obtaining a decrease in operative timing (P = .0409) and hospital stay (P = .0412) (Fig. 2b) with similar rates of immediate postoperative complications, without ICU admissions. Conclusions: An adapted algorithm for the treatment of HCC to COVID outbreak permitted to manage safely these patients by identifying those most at risk of evolution of the neoplastic disease.

Micronvasive behaviour of single small hepatocellular carcinoma: which treatment?

BACKGROUND: Microinvasion (MI), defined as infiltration of the portal or hepatic vein or bile duct and intrahepatic metastasis are accurate indicators of a poor prognosis for mall hepatocellular carcinomas (HCC). A previous study showed that intraoperative ultrasound (IOUS) definition of MI-HCC had a high concordance with histological findings. Aim of this study is to evaluate overall survival and recurrence patterns of patients with MI-HCC submitted to hepatic resection (HR) or laparoscopic ablation therapies (LAT). METHODS: A total of 171 consecutive patients (78 h; 93 LAT) with single, small HCC (< 3 cm) with a MI pattern at IOUS examination were compared analyzing overall survival and recurrence patterns using univariate and multivariate analysis and weighting by propensity score. RESULTS: Overall recurrences were similar in the 2 groups (HR: 51 patients (65%); LAT: 66 patients (71%)). The rate of local tumor progression in the HR group was very low (5 pts; 6%) in comparison to LAT group (22 pts; 24%; p = 0.002). The overall survival curves of HR are significantly better than that of the LAT group (p = 0.0039). On the propensity score Cox model, overall mortality was predicted by the surgical treatment with a Hazard ratio 1.68 (1.08-2.623) (p = 0.022). CONCLUSIONS: If technically feasible and in patients fit for surgery, HR with an adequate tumor margin should be preferred to LAT in patients with MI-HCC at IOUS evaluation, to eradicate MI features near the main nodule, which are relatively frequent even in small HCC (< 3 cm).