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.

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.

The role of HIPEC in the treatment of peritoneal carcinomatosis from gastric cancer: between lights and shadows.

Gastric cancer is one of the most dreadful neoplastic diseases and remains the second cause of cancer death worldwide. Patients who develop peritoneal metastasis have a poor prognosis, with a median survival of less than 6 months. Despite being the cause of 60% of deaths from gastric cancer, peritoneal metastasis can still be considered a local disease and a local multidisciplinary approach can improve the prognosis even in this end-stage disease. At present, hyperthermic intraperitoneal chemotherapy (HIPEC) is the most widely accepted treatment for peritoneal surface diseases and can be performed in patients with different stages of cancer and with various antitumoral drugs. We performed a systematic review of the current status of HIPEC in the treatment of gastric peritoneal metastasis in an attempt to obtain answers to the questions that still remain: do results differ with these different methods? Does HIPEC exert a significant effect on the intracavitary delivery of drugs? Which patients should be treated and which should not? What can we expect from this approach in terms of survival, morbidity, and mortality? On reviewing the literature, despite the lack of trials comparing the different methods, we found that HIPEC has been shown to be an effective tool whenever a complete or an almost complete resection of the peritoneal implants can be performed. Therefore, it is advisable to refer all at-risk patients to specialized centers to be enrolled in randomized trials to achieve truly reliable results.

Radical cholecystectomy without liver resection for peritoneal side early incidental gallbladder cancer.

Gallbladder cancer (GBC) is a rare disease with a poor prognosis. Simple cholecystectomy may be an adequate treatment only for very early disease (Tis, T1a), whereas reoperation is recommended for more advanced disease (T1b and T2). Radical cholecystectomy should have two fundamental objectives: To radically resect the liver parenchyma and to achieve adequate clearance of the lymph nodes. However, recent studies have shown that compared with lymph node dissection alone, liver resection does not improve survival outcomes. The oncological roles of lymphadenectomy and liver resection is distinct. Therefore, for patients with incidental GBC without liver invasion, hepatic resection is not always mandatory.

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.

Giant gastrointestinal stromal tumor (GIST) of the stomach cause of high bowel obstruction: surgical management.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) represent 85% of all mesenchymal neoplasms that affect the gastrointestinal (GI) tract. These GISTs range in size from small lesions to large masses. Often they are clinically silent until they reach a significant size, so their discovery is usually incidental. CASE PRESENTATION: A 67-year-old man was admitted at our general surgery department with a persistent abdominal pain in the left hypochondrium, associated with nausea and vomiting. Clinical examination revealed a palpable mass in the epigastrium and in the left hypochondrium, which was approximately 40 cm long. Ultrasonography and computed tomography of the abdomen showed a large mass of 40 × 25 cm, which extended from the posterior wall of the stomach to the spleen, involving the body and the tail of the pancreas. The patient underwent en-block resection of the mass, sleeve resection of the stomach, and distal pancreatectomy-splenectomy. The histopathology of the resected specimen was consistent with a gastrointestinal stromal tumor of the stomach (positive for CD 117) with a high risk of malignancy (mitotic count >5/50 high-power fieldand Ki67/Mib1 >10%). The postoperative course was uneventful and treatment with imatinib mesylate began immediately. The patient appears to be disease free after four years. CONCLUSIONS: Giant GISTs of the stomach are rare. Surgical resection with curative intent is feasible. The combination of surgical resection and imatinib can provide long-termdisease-free survival. An R0 resection is the best achievable treatment, therefore the patient should be evaluated over time for potential resectability.

Prognostic factors in elderly patients with breast cancer.

BACKGROUND: Breast cancer (BC) remains principally a disease of old ages; with 35-50% of cases occurring in women older than 65 years. Even mortality for cancer increases with aging: 19.7% between 65 and 74 years; 22.6% between 75 and 84 years; and 15.1% in 85 years or more. METHODS: A search was performed on Medline, Embase, Scopus using the following Key words: Breast cancer, Breast neoplasms, Aged, Elder, Elderly, Eldest, Older, Survival analysis, Prognosis, Prognostic factors, Tumor markers, Biomarkers, Comorbidity, Geriatric assessment, Axilla, Axillary surgery. 3029 studies have been retrieved. Paper in which overall or disease free survival were not end points, or age class was not well defined, or the sample was too small, were excluded. At last 42 papers fulfilled the criteria. RESULTS AND DISCUSSION: Lack of screening and delay in diagnosis may be responsible for the minor improvement in survival observed in elderly respect to younger breast cancer patients. Predictive factors are the same and must be assessed with the same attention reserved to younger women. CONCLUSIONS: Most of elderly patient are fit to undergo standard treatment and can get the same benefits of younger women. Nevertheless it is possible that some older women with early breast cancer can be spared too aggressive treatments. Geriatric assessment and co-morbidities can affect the prognosis modifying surveillance, life expectancy and compliance to therapies. They can thus be useful to select the better treatment, either surgical or radio or hormone - or chemo-therapy.

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.

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.

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.

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.

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.

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.

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.

Multicentric evaluation by Verbal Rate Scale and EuroQoL-5D of early and late post-operative pain after TAPP and TEP procedures with mechanical fixation for bilateral inguinal hernias.

Aimed to evaluate the postoperative pain and other complications among two cohorts of patients undergone transabdominal preperitoneal (TAPP) and totally extraperitoneal (TEP) laparoscopic hernia repairs with mechanical fixation, the chart of 305 TAPP and 134 TEP for bilateral not recurrent inguinal hernias were reviewed. The postoperative pain was assessed by using the Verbal Rating Scale (VRS) at one week, one month, 3 months ad six months postoperatively. A subgroup of 60 patients was also administered the QoL EQ-5D questionnaire and follow up for at least 6 months. We found a statistically significant difference in the first day (p = 0.001), in the 7th day (p = 0.002), 30th, and 90th day (p = 0.008) between patients perception of pain in TAPP group and TEP group, but after the 180th day there was not any considerable distinction. On the short term the postoperative pain seems slightly lesser in TEP group.

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.