Inflammatory Pseudotumor of the Liver or Intrahepatic Cholangiocarcinoma, That's the Question: A Review of the Literature.

An inflammatory pseudotumor of the liver is a rare tumor-like lesion composed of polymorphous inflammatory cell infiltrates and variable amounts of fibrosis that can often mimic a malignant liver neoplasm. The etiology of inflammatory pseudotumors of the liver is unknown; symptoms are faint and imaging non-specific. Thus, it is often hard to make a diagnosis preoperatively and it is not so rare to over-treat patients with this disease or vice versa. Thus, more profound knowledge is necessary to plan appropriate disease management. We reported our two cases and systematically searched the literature regarding IPTL. We selected articles published in English from four databases, PubMed, Scopus, Web of Science and Google Scholar, and we included only articles with consistent data. Twenty nine papers fulfilling criteria for the review were selected. The analysis of 69 cases published from 1953 confirmed that the risk factors are unclear, the imaging data is not specific, and biopsy is crucial but not so widely used in clinical practice due to the procedure's related risks, and relatively low effectiveness and improvement in imaging analysis. Regarding treatment, surgeons have moved towards a more conservative attitude over the years due to better imaging quality and patient surveillance. However, surgery remains the modality of choice for most cases with an indeterminate diagnosis. Even if an inflammatory pseudotumor of the liver is a benign tumor with a good prognosis, not requiring any treatment in most cases, sometimes it remains challenging to differentiate it from ICC; therefore, there is a solid recommendation to manage this condition with a multidisciplinary team.

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.

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.

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.

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.

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.

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.

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.