Detection and Real-Time Surgical Assessment of Colorectal Liver Metastases Using Near-Infrared Fluorescence Imaging during Laparoscopic and Robotic-Assisted Resections.

BACKGROUND: The European Association of Endoscopic Surgery (EAES) recommends, with strong evidence, the use of indocyanine green (ICG) fluorescence imaging combined with intraoperative ultrasound (IOUS) to improve identification of superficial liver tumors. This study reports the use of ICG for the detection of colorectal liver metastases (CRLMs) during minimally invasive liver resection. METHODS: A single-center consecutive series of minimally invasive (laparoscopic and robotic) hepatic resections for CRLMs was prospectively evaluated (April 2019 and October 2023). RESULTS: A total of 25 patients were enrolled-11 undergoing laparoscopic and 14 undergoing robotic procedures. The median age was 65 (range 50-85) years. Fifty CRLMs were detected: twenty superficial, eight exophytic, seven shallow (<8 mm from the hepatic surface), and fifteen deep (>10 mm from the hepatic surface) lesions. The detection rates of CRLMs through preoperative imaging, laparoscopic ultrasound (LUS), ICG fluorescence, and combined modalities (ICG and LUS) were 88%, 90%, 68%, and 100%, respectively. ICG fluorescence staining allowed us to detect five small additional superficial lesions (not identified with other preoperative/intraoperative techniques). However, two lesions were false positive fluorescence accumulations. All rim fluorescence pattern lesions were CRLMs. ICG fluorescence was used as a real-time guide to assess surgical margins during parenchymal-sparing liver resections. All patients with integrity of the fluorescent rim around the CRLM displayed a radical resection during histopathological analysis. Four patients (8%) with a protruding rim or residual rim patterns had positive resection margins. CONCLUSIONS: ICG fluorescence imaging can be integrated with other conventional intraoperative imaging techniques to optimize intraoperative staging. Rim fluorescence proved to be a valid indicator of the resection margins: by removing the entire fluorescent area, a tumor-negative resection (R0) is achieved.

Robotic Total Mesorectal Excision for Low Rectal Cancer: A Narrative Review and Description of the Technique.

Robotic surgery may offer significant advantages for treating extraperitoneal rectal cancer. Although laparoscopy has been shown to be safe and effective, laparoscopic total mesorectal excision (TME) remains technically challenging and is still performed in selected centers. Robotic anterior resection (RAR) may overcome the drawback of conventional laparoscopy, providing high-quality surgery with favorable oncological outcomes. Moreover, recent data show how RAR offers clinical and oncological benefits when affording difficult TMEs, such as low and advanced rectal tumors, in terms of complication rate, specimen quality, recurrence rate, and survival. This series aims to review the most recent and relevant literature, reporting mid- and long-term oncological outcomes and focusing on minimally invasive RAR for low rectal cancer.

Prior Robotic Console Expertise May Improve Basic Skills at the New Hugo RAS Simulator: Results from a Cohort Trial and Implications for Skill Transference Across Platforms.

Background: Robot-assisted surgery ensures minimal invasiveness; since the expiry of the Da Vinci patent, new robotic systems have entered the market. Recently, the Hugo RAS received CE approval for several surgical procedures. However, more is needed to know about skill acquisition at the new simulator. Objective: This study aims to analyse the factors impacting basic surgical skills at the Hugo RAS simulator. Design setting and participants: We present a cross-sectional study involving 71 participants of different backgrounds invited to a hands-on session with the Hugo RAS simulator voluntarily. All of them had no prior expertise with the system. Participants were recruited among medical/nurse students, residents, and laparoscopic and robotic surgeons. Intervention: All participants underwent a hands-on "pick and place" exercise at the Hugo RAS simulator; the metrics of a second-round pick and place exercise were recorded. Outcome measurements and statistical analysis: Metrics were analysed with regard to the following variables: demographics, videogame use, and prior surgical experience (no surgical expertise, experience with laparoscopy, and experience with robotic console). Results and limitations: All participants completed the test. Of them, 77.5% were naïve to surgery, 8.5% had prior laparoscopic expertise, and 14.1% had prior robotic console experience. The time to complete the pick and place exercise was significantly lower (p < 0.001) among prior robotic surgeons (38 s, interquartile range [IQR] 34-45) compared with both naïve participants (61 s, IQR 53-71) and laparoscopists (93 s, IQR 53-162). The overall score of the exercise decreased with age (p = 0.046); however, the overall scores were significantly and steadily higher among surgeons experienced in robotic consoles across all age groups (p = 0.006). Neither gender (p = 0.7) nor videogame use (p = 0.9) correlated significantly with the metrics. Conclusions: This is the first study analysing factors impacting basic skill acquisition at a new robotic simulator. Experience with robotic consoles may represent a major factor, raising the hypothesis of the transferability of basic robotic skills across different robotic systems. Further studies are required to explore this issue. Patient summary: In the present study, we analysed which characteristics may affect the basic surgical skills at a novel robotic platform.

Utility of near infrared fluorescent cholangiography in detecting biliary structures during challenging minimally invasive cholecystectomy.

BACKGROUND: Surgeons can minimize the risk of bile duct injury (BDI) during challenging mini-invasive cholecystectomy through technical standardization by means of a precise anatomical landmark identification (Critical View of Safety) and advanced technology for biliary visualization. Among these systems, the adoption of magnified stereoscopic 3-dimensional view provided by robotic platforms and near infrared fluorescent cholangiography (NIRF-C) is the most promising. METHODS: In this prospective cohort study, we evaluated all consecutive minimally invasive cholecystectomies (laparoscopic and robotic) performed with NIRF-C between May 2022 and January 2023 at General Surgery Unit, Department of Health Sciences, University of Milan, San Paolo Hospital (Milan, Italy). Inclusions criteria were as follows: (1) acute cholecystitis (emergency group), (2) history of chronic cholecystitis or complicated cholelithiasis (deferred urgent group), (3) difficult cases (patients affected by cirrhosis, with scleroatrophic gallbladder or BMI > 35 kg/m2). For each group, the detection rate and visualization order of the main biliary structures were reported (cystic duct, CD; common hepatic duct, CHD; common bile duct, CBD; and CD-CHD junction). RESULTS: A total of 101 consecutive patients were enrolled, including 83 laparoscopic and 18 robotic cholecystectomies. All patients were stratified into three subgroups: (a) emergency group (n = 33, 32.7%), (b) deferred urgent group (n = 46, 45.5%), (c) difficult group (n = 22, 21.8%). Visualization of at least one biliary structure was possible in 94.1% of cases (95/101). Interestingly, all four main structures were detected in 43.6% of cases (44/101). The CD was the structure identified most frequently, being recognized in 91/101 patients (90.1%), followed by CBD (83.2%), CHD (62.4%), and CD-CHD junction (52.5%). In the subset of patients that underwent emergency surgery for AC, the CD-CHD confluence was identified in only 45.5% of cases. However, early and precise identification of CBD (75.8%) and CD (87.9%) allowed safe isolation, clipping, and transection of the cystic duct. In the deferred urgent group, the CBD and the CD were easily identified as first structure in a high percentage of cases (65.2% and 41.3% respectively), whereas the CD-CHD junction was the third structure to be identified in 67.4% of cases, the highest value among the three subgroups. In the difficult group, NIRF-C did not prove to be a useful tool for biliary visualization. The rates of failure of visualization were elevated: CBD (27.3%), CD (18.2%), CHD (54.5%), and CD-CHD (68.2%). CONCLUSIONS: NIRF-C is a powerful real-time diagnostic tool to detect CBD and CD during minimally invasive cholecystectomy, especially when inflammation due to acute or chronic cholecystitis subverted the anatomy of the hepatoduodenal ligament.

Ceramide present in cholangiocarcinoma-derived extracellular vesicle induces a pro-inflammatory state in monocytes.

Cholangiocarcinoma (CCA) is a rare cancer characterized by a global increasing incidence. Extracellular vesicles (EV) contribute to many of the hallmarks of cancer through transfer of their cargo molecules. The sphingolipid (SPL) profile of intrahepatic CCA (iCCA)-derived EVs was characterized by liquid chromatography-tandem mass spectrometry analysis. The effect of iCCA-derived EVs as mediators of inflammation was assessed on monocytes by flow cytometry. iCCA-derived EVs showed downregulation of all SPL species. Of note, poorly-differentiated iCCA-derived EVs showed a higher ceramide and dihydroceramide content compared with moderately-differentiated iCCA-derived EVs. Of note, higher dihydroceramide content was associated with vascular invasion. Cancer-derived EVs induced the release of pro-inflammatory cytokines in monocytes. Inhibition of synthesis of ceramide with Myriocin, a specific inhibitor of the serine palmitoyl transferase, reduced the pro-inflammatory activity of iCCA-derived EVs, demonstrating a role for ceramide as mediator of inflammation in iCCA. In conclusion, iCCA-derived EVs may promote iCCA progression by exporting the excess of pro-apoptotic and pro-inflammatory ceramides.

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.

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.

Defective DNAM-1 Dependent Cytotoxicity in Hepatocellular Carcinoma-Infiltrating NK Cells.

BACKGROUND: Natural killer (NK) cells play a key role in immune surveillance and response to tumors, their function regulated by NK cell receptors and their ligands. The DNAM-1 activating receptor recognizes the CD155 molecule expressed in several tumor cells, such as hepatocellular carcinoma (HCC). This study aims to investigate the role of the DNAM-1/CD155 axis in mediating the NK cell response in patients with HCC. METHODS: Soluble CD155 was measured by ELISA. CD155 expression was sought in HCC cells by immunohistochemistry, qPCR, and flow cytometry. DNAM-1 modulation in NK cells was evaluated in transwell experiments and by a siRNA-mediated knockdown. NK cell functions were examined by direct DNAM-1 triggering. RESULTS: sCD155 was increased in sera from HCC patients and correlated with the parameters of an advanced disease. The expression of CD155 in HCC showed a positive trend toward better overall survival. DNAM-1 downmodulation was induced by CD155-expressing HCC cells, in agreement with lower DNAM-1 expressions in tumor-infiltrating NK (NK-TIL) cells. DNAM-1-mediated cytotoxicity was defective both in circulating NK cells and in NK-TIL of HCC patients. CONCLUSIONS: We provide evidence of alterations in the DNAM-1/CD155 axis in HCC, suggesting a possible mechanism of tumor resistance to innate immune surveillance.

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.

MICA/B-targeted antibody promotes NK cell-driven tumor immunity in patients with intrahepatic cholangiocarcinoma.

The major histocompatibility complex-class I chain related proteins A and B (MICA/B) is upregulated because of cellular stress and MICA/B shedding by cancer cells causes escape from NKG2D recognition favoring the emergence of cancers. Cholangiocarcinoma (CCA) is a relatively rare, though increasingly prevalent, primary liver cancer characterized by a late clinical presentation and a dismal prognosis. We explored the NKG2D-MICA/B axis in NK cells from 41 patients with intrahepatic cholangiocarcinoma (iCCA). The MICA/B-specific 7C6 mAb was used for ex vivo antibody-dependent cytotoxicity (ADCC) experiments using circulating, non tumor liver- and tumor-infiltrating NK cells against the HuCCT-1 cell line and patient-derived primary iCCA cells as targets. MICA/B were more expressed in iCCA than in non-tumoral tissue, MICA transcription being higher in moderately-differentiated compared with poorly-differentiated cancer. Serum MICA was elevated in iCCA patients in line with higher expression of ADAM10 and ADAM17 that are responsible for proteolytic release of MICA/B from tumor. Addition of 7C6 significantly boosted peripheral, liver- and tumor-infiltrating-NK cell degranulation and IFNγ production toward MICA/B-expressing established cell lines and autologous iCCA patient target cells. Our data show that anti-MICA/B drives NK cell anti-tumor activity, and provide preclinical evidence in support of 7C6 as a potential immunotherapeutic tool for iCCA.

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.

Fluorescent cholangiography: An up-to-date overview twelve years after the first clinical application.

Laparoscopic cholecystectomy (LC) is one of the most frequently performed gastrointestinal surgeries worldwide. Bile duct injury (BDI) represents the most serious complication of LC, with an incidence of 0.3%-0.7%, resulting in significant perioperative morbidity and mortality, impaired quality of life, and high rates of subsequent medico-legal litigation. In most cases, the primary cause of BDI is the misinterpretation of biliary anatomy, leading to unexpected biliary lesions. Near-infrared fluorescent cholangiography is widely spreading in clinical practice to delineate biliary anatomy during LC in elective and emergency settings. The primary aim of this article was to perform an up-to-date overview of the evolution of this method 12 years after the first clinical application in 2009 and to highlight all advantages and current limitations according to the available scientific evidence.

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.

Application of Indocyanine Green Fluorescence as an Adjuvant to Laparoscopic Ultrasound in Minimally Invasive Liver Resection.

Background: Indocyanine green (ICG) fluorescence imaging has been extensively used in a variety of applications in visceral surgery. In minimally invasive liver resections, the detection of small superficial hepatic lesions using an intravenous injection of ICG before surgery represents a promising application. Methods: We analyzed 18 consecutive patients who underwent laparoscopic liver resection for superficial malignant tumors, namely 11 patients with hepatocellular carcinoma (HCC), 5 patients with colorectal liver metastases (CRLM), 1 patient with intrahepatic cholangiocarcinoma (ICC), and 1 patient with thyroid cancer metastasis, using ICG fluorescence as an adjuvant tool to intraoperative laparoscopic ultrasound (LUS). Results: An optimal ICG 15-minute clearance retention rate (R15 < 10%) and ICG plasma disappearance rate (<18%/minute) were present in 11 patients (61.1%) and in 14 patients (77.7%), respectively. Liver tumors were 29 in total, including 14 HCCs (48.3%), 13 CRLMs (44.8%), 1 ICC (3.4%), and 1 thyroid cancer metastasis (3.4%). Twenty-nine tumors (100%) were correctly visualized with ICG/fluorescence, as compared with 21 tumors identified with LUS (72.4%). After complete liver mobilization, ICG staining allowed to identify more superficial lesions (early HCC and small CRLM) in posterolateral segments (Segments 6 and 7) as compared with LUS (14 versus 10 lesions). In addition, in segments usually treated laparoscopically (e.g., left lateral segments), ICG was superior to LUS (10 versus 6 lesions) to identify superficial early HCC in patients with macronodular cirrhosis. Conclusions: ICG visual feedback might substitute the tactile feedback of the hand and might in some cases act as a "booster" of LUS for superficial hepatic lesions.

An Anti-MICA/B Antibody and IL-15 Rescue Altered NKG2D-Dependent NK Cell Responses in Hepatocellular Carcinoma.

Natural killer (NK) cells play a pivotal role in cancer immune surveillance, and activating the receptor/ligand interaction may contribute to control the development and evolution of hepatocellular carcinoma (HCC). We investigated the role of the natural killer group 2 member D (NKG2D) activating receptor and its ligand, the major histocompatibility complex class I chain-related protein A and B (MICA/B) in patients with cirrhosis and HCC subjected to surgical resection, patients with cirrhosis and no HCC, and healthy donors (HD). The NKG2D-mediated function was determined in peripheral blood (PB), in tumor-infiltrating lymphocytes (NK-TIL), and in matched surrounding liver tissue (NK-LIL). A group of patients treated with sorafenib because of clinically advanced HCC was also studied. A humanized anti-MICA/B monoclonal antibody (mAb) was used in in vitro experiments to examine NK cell-mediated antibody-dependent cellular cytotoxicity. Serum concentrations of soluble MICA/B were evaluated by ELISA. IL-15 stimulation increased NKG2D-dependent activity which, however, remained dysfunctional in PB NK cells from HCC patients, in line with the reduced NKG2D expression on NK cells. NK-TIL showed a lower degranulation ability than NK-LIL, which was restored by IL-15 stimulation. Moreover, in vitro IL-15 stimulation enhanced degranulation and interferon-γ production by PB NK from patients at month one of treatment with sorafenib. Anti-MICA/B mAb associated with IL-15 was able to induce PB NK cytotoxicity for primary HCC cells in HD and patients with HCC, who also showed NK-TIL degranulation for autologous primary HCC cells. Our findings highlight the key role of the NKG2D-MICA/B axis in the regulation of NK cell responses in HCC and provide evidence in support of a potentially important role of anti-MICA/B mAb and IL-15 stimulation in HCC immunotherapy.

Correction to: Immunohistochemical evaluation of microsatellite instability in resected colorectal liver metastases: a preliminary experience.

The original version of this article unfortunately contained a mistake. All the authors first name and second name has been inadvertently interchanged. Now the authors name are corrected.

The role of E-cadherin expression in the treatment of western undifferentiated early gastric cancer: Can a biological factor predict lymph node metastasis?

The use of endoscopic techniques to cure small sized, well differentiated early gastric cancer has been adopted worldwide. In the Eastern world, endoscopic resection is being increasingly utilized to treat small undifferentiated early gastric cancer according to the extended criteria proposed by the Japanese Gastric Cancer Associations. However, studies in the Western world reported in these tumors a rate of nodal metastasis ranging between 5% and 20%, that is higher of those observed in Eastern counterparts. A tool to predict the risk of nodal dissemination would be of great use to guide treatment toward endoscopic resection. In our study, we propose E-cadherin expression as a biological factor to predict lymph node involvement. We retrospectively reviewed the E-cadherin (E-cad) expression profile of all histological specimens of undifferentiated early gastric cancer from two Oncologic Departments and compared it with several tumor characteristics. A total of 39 patients with early gastric cancer met the inclusion criteria, of which 16 (41%) pT1a, and 23 (58.9%) pT1b SM1. Thirty-two patients (82%) underwent subtotal gastrectomy, whereas total gastrectomy was performed in only seven cases (17.9%). Patients were divided into two groups: low E-cad expression (E-cad 0/1+, 10 patients) and high E-cad expression (E-cad 2+/3+, 29 patients) according to the immunohistochemical assay (ICH). On univariate analysis, we found an association between low E-cad expression and low grading tumor (p = 0.019), pure undifferentiated histotype (PU-type) (p = 0.014), and lymph node involvement (N+) (p < 0.001). The association between low E-cad expression and lymph node metastasis was confirmed by multivariate analysis (OR = 14.5, 95% CI 3.46-60.76, p < 0.001). The loss of expression of E-cad may be a simple biological factor to predict lymph nodes metastasis in patients with undifferentiated early gastric cancer. Additional larger prospective studies are necessary to confirm these findings.

Laparoscopic thermoablation for hepatocellular carcinoma in patients with liver cirrhosis: an effective procedure for tricky tumors.

The optimal treatment for hepatocellular carcinoma (HCC) is surgical resection. However, only a small percentage of patients are amenable to this option. Percutaneous radiofrequency interstitial thermal ablation (TA) proved to be effective in the treatment of unresectable HCC. Recent advances in laparoscopic ultrasound have improved the accuracy in detecting small intrahepatic HCC nodules missed by pre-operative imaging techniques. Our objective was to evaluate an operative combination of laparoscopic ultrasound with laparoscopic thermoablation (LTA) in the treatment of HCC not amenable to liver resection. The aim of our review was to evaluate the advantages and limits of the laparoscopic approach according the criteria of the evidence-based medicine. LTA of HCC proved to be a safe and effective technique both in the short- and long-term follow-up period. This technique may be indicated in selected cases when the percutaneous approach to the lesion is very difficult or contraindicated.

Totally Laparoscopic Radical Cholecystectomy for Gallbladder Cancer: A Single Center Experience.

Background: Primary laparoscopic approach for the treatment of cancers of the biliary tract is not popular in the surgical community. The aim of this study is to report the short-term data of patients who underwent total laparoscopic radical cholecystectomy for gallbladder cancer (GBC) at a single center of specialized hepatobiliary surgery. Methods: From November 2016 to January 2019, we routinely performed a laparoscopic approach for two groups of patients: (1) patients with primary GBC (diagnosed preoperatively) and (2) patients with incidental GBC (IGBC) discovered after cholecystectomy. Results: Our retrospective study included 18 patients (7 primary GBCs, 11 IGBCs). Conversion rate from laparoscopy to laparotomy was 28.6% and 9.1%, respectively, for the two groups, but this difference was not statistically significant (P = .28). Only 3 patients had liver recurrence (27.3%) and 1 had liver invasion (14.3%). A more advanced T category and TNM stage were presented in the preoperative suspicion cases (T3-T4 18.2% versus 57.1%, P = .06, stage IVA-B 9.1% versus 71.4%, P = .017). Regional lymphadenectomy was performed in 15 patients, in 73.3% the total number of lymph nodes (total LNs) retrieved was more than 7 (7-12 LNs in 66.7% of patients and >12 LNs in 6.6% of patients). The mean postoperative long stay was 8 days excluding for cases who developed complication. Conclusions: Laparoscopy can be considered a safe treatment for IGBC or primary GBC. The T3 stage with only liver involvement was not a contraindication. The real reasons that lead to convert the laparoscopic procedure were due to oncological concerns, unrelated to the liver infiltration.

Hem-o-Lok clip migration into the duodenum after laparoscopic digestive surgery: a systematic review.

INTRODUCTION: The wide use of hemoclips during laparoscopic surgery has led to a variety of unusual complications, among these, there is the migration of Hem-o-Lok clip into the duodenum. We performed a literature review of all cases of Hem-o-Lok clip migration into the duodenum after laparoscopic digestive surgery reported in literature. EVIDENCE ACQUISITION: All relevant articles were extracted up to June 2019 based on the results of searches in MEDLINE, PubMed, Scopus, Web of Science and Google Scholar. EVIDENCE SYNTHESIS: At the time of this review, a total of seven cases have been described. The mean age was 49 years and the majority of these patients were women (57%). Previous laparoscopic surgery was performed for cholecystectomy (four patients), cholecystectomy with common bile duct exploration (one patient), right hemicolectomy (one patient) and distal gastrectomy (one patient). Symptoms occurred from 3 months to 2 years after laparoscopic surgery. The majority of patients developed symptoms of bowel occlusion and abdominal pain. Three patients remained asymptomatic. In many cases the Hem-o-Lok wedged into the wall of the first or second portion of the duodenum. In all cases, esophageal gastroduodenoscopy was the primary modality to make the diagnosis. Initial treatment was conservative with watch-and-wait strategy or proton pump inhibitors followed by endoscopic removal, while surgical treatment was required in two cases. CONCLUSIONS: The application of Hem-o-Lok clip during laparoscopic surgery is safe and effective. Postoperative Hem-o-Lok migration into the duodenum is rare. The treatment could be conservative in the majority of cases.