Novel navigation for laparoscopic cholecystectomy fusing artificial intelligence and indocyanine green fluorescent imaging.

This preliminary study is the first to demonstrate that AI can precisely identify loose connective tissue during laparoscopic cholecystectomy and ICG fluorescent cholangiography. Tashiro and colleagues conclude that this novel real-time navigation modality fusing AI and ICG fluorescent imaging may enhance safety and provide more reliable laparoscopic or robotic surgery.

Color-coded laparoscopic liver resection using artificial intelligence: A preliminary study.

Tashiro and colleagues demonstrated for the first time that an artificial intelligence system can precisely identify intrahepatic vascular structures during laparoscopic liver resection in real time through color coding under bleeding and indocyanine green fluorescent imaging. The system supports real-time navigation and offers potentially safer laparoscopic or robotic liver surgery.

Development of a Novel Artificial Intelligence System for Laparoscopic Hepatectomy.

BACKGROUND/AIM: Laparoscopic hepatectomy (LH) requires accurate visualization and appropriate handling of hepatic veins and the Glissonean pedicle that suddenly appear during liver dissection. Failure to recognize these structures can cause injury, resulting in severe bleeding and bile leakage. This study aimed to develop a novel artificial intelligence (AI) system that assists in the visual recognition and color presentation of tubular structures to correct the recognition gap among surgeons. PATIENTS AND METHODS: Annotations were performed on over 350 video frames capturing LH, after which a deep learning model was developed. The performance of the AI was evaluated quantitatively using intersection over union (IoU) and Dice coefficients, as well as qualitatively using a two-item questionnaire on sensitivity and misrecognition completed by 10 hepatobiliary surgeons. The usefulness of AI in medical education was qualitatively evaluated by 10 medical students and residents. RESULTS: The AI model was able to individually recognize and colorize hepatic veins and the Glissonean pedicle in real time. The IoU and Dice coefficients were 0.42 and 0.53, respectively. Surgeons provided a mean sensitivity score of 4.24±0.89 (from 1 to 5; Excellent) and a mean misrecognition score of 0.12±0.33 (from 0 to 4; Fail). Medical students and residents assessed the AI to be very useful (mean usefulness score, 1.86±0.35; from 0 to 2; Excellent). CONCLUSION: The novel AI presented was able to assist surgeons in the intraoperative recognition of microstructures and address the recognition gap among surgeons to ensure a safer and more accurate LH.

Laparoscopic Anatomical Liver Resection Using Liver Mapping of Incidental Indocyanine Green Fluorescence due to Cholestasis.

BACKGROUND/AIM: Indocyanine green (ICG) fluorescence is useful in laparoscopic hepatectomy (LH) for tumor identification and staining, as well as determination of resection margins. At our Institution, patient-specific, three-dimensional simulations and rehearsal of surgical strategies are carried out preoperatively. We describe cases in which ICG administered preoperatively became stagnated and fluoresced in an area similar to the preoperatively established resection area and the pathological findings in these cases. PATIENTS AND METHODS: Four patients who underwent LH at our hospital between 2020 and 2023 (due to hepatocellular carcinoma in two and colorectal liver metastasis in two) were enrolled in the present study. The ICG-fluorescing liver segments were resected laparoscopically and their pathological characteristics were examined using a fluorescence microscope. RESULTS: In four cases, the areas of ICG fluorescence seen intraoperatively were due to stasis of preoperatively administered ICG, which fortuitously was equivalent to the planned resection area in the preoperative patient-specific simulation. The fluorescent areas were resected; there were no cases of bile leakage or recurrence. Fluorescence microscopy revealed areas with diffuse ICG fluorescence in normal hepatocytes on the tumor's peripheral side. CONCLUSION: It was suggested that resection of the liver area that was fluorescent due to stagnation of preoperatively administered ICG was rational and justified both anatomically and oncologically. This resection may also contribute to the prevention of bile leakage and recurrence.

Simultaneous tumor identification, cholangiography, and securing surgical margin for recurrence of hepatocellular carcinoma using the Medical Imaging Projection System.

BACKGROUND: Indocyanine green (ICG) fluorescence-guided surgery is a real-time navigation technology for tumor detection, securing surgical margins, segmentation mapping, and cholangiography in liver surgery [1]. According to recent reports, the Medical Imaging Projection System (MIPS) may be a useful new real-time navigation technology for open anatomical liver resection [2]. However, the efficacy of MIPS for tumor identification, cholangiography, and securing surgical margins is uncertain. In this report, we introduce MIPS-assisted liver resection for real-time navigation during simultaneous tumor identification, cholangiography, and securing surgical margins. METHODS: A 76-year-old man presented with a 30 × 30 mm recurrent hepatocellular carcinoma on the transection plane after right anterior sectionectomy. Eight radiofrequency ablations were performed after the first hepatectomy. Preoperative computed tomography and three-dimensional simulation revealed a tumor near the posterior Glissonean branch. One day before surgery, 2.5 mg/body ICG was administered. We analyzed whether MIPS could simultaneously facilitate tumor identification, cholangiography, and securing surgical margins. The relationship between fluorescent imaging and the surgical margin was evaluated with a fluorescent microscope [3]. RESULTS: Simultaneous tumor identification, cholangiography, and securing the surgical margins were demonstrated by adjusting the image projection of MIPS, and R0 resection was achieved without biliary injury (Figs. 1 and 2). The operative time and estimated blood loss were 287 minutes and 394 mL, respectively. He was discharged on postoperative day 12 without any complications. CONCLUSION: MIPS could be useful for real-time navigation for tumor identification, cholangiography, and securing surgical margins during liver surgery. The threshold of fluorescent intensity should be set for optimal image projection.

Comparison of Endotoxin Activity Assay and Various Biomarkers for Severity Assessment in Colorectal Perforation Patients.

Colorectal perforation is a serious disease with high mortality requiring emergency surgery. This study aimed to evaluate the role of the endotoxin activity assay (EAA) to assess the severity in patients admitted to the intensive care unit after emergency surgeries for colorectal perforations. Patients were divided into high (EAA ≥.4) and low (EAA <.4) groups based on the EAA levels, and the correlation between the EAA values and clinical variables related to the severity was evaluated. The SOFA scores were significantly higher in the high group than those in the low group. The high EAA value persisted even after 48 hours and extended the ICU length of stay. These results suggest that EAA may be a potential biomarker to assess severity and useful as one of the instrumental in predicting the outcomes for colorectal perforation patients.

Laparoscopic Resection of a Hepatic Epithelioid Angiomyolipoma Revealed by Indocyanine Green Fluorescence Imaging.

Indocyanine green fluorescence imaging (ICG-FI)-a sensitive tool for detecting tumor localization in laparoscopic surgery-produces false positive results for benign liver tumors. This report is the first case of hepatic angiomyolipoma (HAML) treated laparoscopically with ICG-FI. We present the case of a 31-year-old woman with a liver tumor that was a 13-mm mass in the anterior superior segment. Though a benign tumor was suspected, malignant potential could not be ruled out. Therefore, minimally invasive laparoscopic resection using ICG-FI was planned. ICG, intravenously injected preoperatively, revealed the tumor's existence. Pure laparoscopic hepatectomy with ICG-FI was performed for excisional biopsy, during which the tumor was resected with adequate surgical margins, followed by histological confirmation of HAML. In conclusion, it is suggested that laparoscopic resection with ICG-FI is an effective minimal invasive surgery for tumors that are difficult to detect, such as HAML, leading to a safe surgical margin.

Obesity Strongly Promotes Growth of Mouse MC38 Colon Cancer in an Orthotopic-syngeneic C57BL/6 Mouse Model.

BACKGROUND/AIM: Obesity is a major risk factor for colorectal cancer. The MC38 mouse colon-cancer cell line is a versatile syngeneic model of colon cancer in C57BL/6 mice. In the present study, the influence of a high-fat diet (HFD) on the growth of the MC38 mouse colon-cancer cell line was examined in an orthotopic-transplantation syngeneic model in C57BL/6 mice. MATERIALS AND METHODS: Five 6-week-old C57BL/6 male mice were fed a control diet (CD, 6.5% fat) or HFD (34.3% fat) for eight weeks. Then, a 2 mm3 fragment of a subcutaneous MC38 tumor was attached to the surface of the cecum of C57BL/6 mice with a single stitch using a 7-0 suture to establish an orthotopic-transplantation model. Each group continued their initial diet for 17 days. RESULTS: The HFD group had more than twice the tumor volume and tumor weight than the CD group (p=0.021 and p=0.014, respectively). CONCLUSION: HFD-induced obesity strongly increased MC38 colon-cancer progression in a C57BL/6 orthotopic-transplantation mouse model. The present study emphasizes the detrimental effect of obesity on coloncancer progression.

Linkage of methionine addiction, histone lysine hypermethylation, and malignancy.

Methionine addiction, found in all types of cancer investigated, is because of the overuse of methionine by cancer cells for excess transmethylation reactions. In the present study, we compared the histone H3 lysine-methylation status and degree of malignancy between methionine-addicted cancer cells and their isogenic methionine-independent revertants, selected by their growth in low concentration of methionine. The methionine-independent revertans can grow on low levels of methionine or independently of exogenous methionine using methionine precursors, as do normal cells. In the methionine-independent revertants, the excess levels of trimethylated histone H3 lysine marks found in the methionine-addicted parental cancer cells were reduced or lost, and their tumorigenicity and experimental metastatic potential in nude mice were also highly reduced. Methionine addiction of cancer is linked with malignancy and hypermethylation of histone H3 lysines. The results of the present study thus provide a unique framework to further understand a fundamental basis of malignancy.

Indocyanine Green Labeling of Tumors in the Liver Recurring After Radiofrequency Ablation Enables Complete Resection by Fluorescence-guided Surgery.

BACKGROUND/AIM: Radiofrequency ablation (RFA) is used to treat primary and metastatic tumors in the liver. However, local recurrence after RFA is frequent and subsequent salvage hepatectomy is often ineffective due to difficulty in visualization of tumor margins. PATIENTS AND METHODS: In the present retrospective clinical trial, seven patients from the Department of General and Gastro-enterological Surgery, Showa University School of Medicine underwent salvage hepatectomy for recurrent hepatocellular carcinoma (HCC) (n=2), colorectal liver metastasis (n=4) and lung-carcinoid liver metastasis (n=1), after RFA, between 2011 and 2020. Tumors were labeled with indocyanine green (ICG) and resected under fluorescence guidance. Resected specimens were evaluated under fluorescence microscopy as well as by standard histopathological techniques. RESULTS: Pathological findings revealed negative tumor margins in all patients after fluorescence-guided surgery. Six of seven resected tumors had a fluorescent rim, including both HCC and liver metastasis. Fluorescence microscopy demonstrated that viable cancer tumor cells were located only on the inside of the fluorescent rim, and no malignant cells were detected within the fluorescent rim surrounding the tumor. Fluorescence microscopy showed that the tumor margin was secured if the fluorescence signal was completely resected. CONCLUSION: The present results demonstrate that ICG labeling of liver tumors recurring after RFA enabled complete resection under fluorescence guidance. The present study is the first clinical study to demonstrate that tumor types that generally cannot be completely resected with bright light are fully resectable under fluorescence guidance.

Determinative Structural Features Identified With Probe-based Confocal Endomicroscopy for the Accurate Diagnosis of Gallbladder Malignancy.

BACKGROUND: Probe-based confocal laser endomicroscopy (pCLE) can visualize microscopic structures at high resolution but has not yet yielded definitive diagnostic features of gallbladder malignancy, as opposed to benign changes. PATIENTS AND METHODS: A total of 73 patients had their gallbladder evaluated with pCLE performed on resected benign and malignant gallbladder surgical specimens, which were sprayed with fluorescein. Malignant and benign features of pCLE findings were identified on the basis of Miami and Paris Classifications. Standard histopathological diagnoses and individual patient pCLE findings of gallbladder lesions were correlated. RESULTS: Of the 73 consecutive patients that had their gallbladder evaluated ex vivo with pCLE, 11 were identified with gallbladder malignancy. pCLE identified features of gallbladders examined ex vivo, including the presence of thick dark bands and dark clumps, which together correlated with histopathologically-determined biliary malignancy at 100% sensitivity. Thick white bands and visualized epithelium, also identified with pCLE, together correlated with histopathologically-determined malignancy at 100% specificity. CONCLUSION: pCLE can be used for real-time differentiation of cancerous/non-cancerous regions in the gallbladder using the diagnostic criteria identified in the present study.

Relationship Between Remnant Pancreatic Volume and Endocrine Function After Pancreaticoduodenectomy.

BACKGROUND: Decreased pancreatic volume (PV) is a predictive factor for diabetes mellitus (DM) after surgery. There are few reports on PV and endocrine function pre- and post-surgery. We investigated the correlation between PV and insulin secretion. METHODS: Seventeen patients underwent pancreaticoduodenectomy (PD) Pre- and post-surgery PV and C-peptide index (CPI) measurements were performed. Additionally, the correlation between PV and CPI was analyzed. RESULTS: The mean preoperative PV (PPV) was 55.1 ± 31.6 mL, postoperative remnant PV (RPV) was 25.3±17.3 mL, and PV reduction was 53%. The mean preoperative C-peptide immunoreactivity (CPR) was 1.39 ± .51 and postoperative CPR was .85±.51. The mean preoperative CPI was 1.29±.72 and postoperative CPI was .73 ± .48. Significant correlations were observed between RPV and post CPR (ρ = .507, P = .03) and post CPI (ρ = .619, P = .008). DISCUSSION: There was a significant correlation between RPV and CPI after PD. A smaller RPV resulted in lower insulin secretion ability, increasing the potential risk of new-onset DM after PD.

Extent and Instability of Trimethylation of Histone H3 Lysine Increases With Degree of Malignancy and Methionine Addiction.

BACKGROUND/AIM: Methionine addiction is a fundamental and general hallmark of cancer, termed the Hoffman effect. Methionine addiction is due to excessive use of and dependence on methionine by cancer cells. In the present report, we correlated the extent of methionine addiction and degree of malignancy with the amount and stability of methylated histone H3 lysine marks. MATERIALS AND METHODS: We established low- and high-malignancy variants from a parental human pancreatic-cancer cell line and compared their sensitivity to methionine restriction and histone H3 lysine methylation status. RESULTS: A low-malignancy, low-methionine-addiction revertant of the parental pancreatic-cancer cell line had less methylated H3K9me3 and was less sensitive to methionine restriction effected by recombinant methioninase (rMETase) than the parental cell line. A high-malignancy variant of the pancreatic cancer cell line had increased methylated H3K9me3 and was more sensitive to methionine restriction by rMETase with regard to inhibition of proliferation and to instability of histone H3 lysine methylation than the parental cell line. Orthotopic malignancy in nude mice was reduced in the low-methionine-addiction revertant and greater in the high-malignancy variant than in the parental cell line. CONCLUSION: The present study indicates that the degree of malignancy is linked to the extent of methionine addiction and the level and instability of trimethylation of histone H3, suggesting these phenomena are linked as a fundamental basis of oncogenic transformation.

Over-methylation of Histone H3 Lysines Is a Common Molecular Change Among the Three Major Types of Soft-tissue Sarcoma in Patient-derived Xenograft (PDX) Mouse Models.

BACKGROUND/AIM: Sarcomas are considered a heterogeneous disease with incomplete understanding of its molecular basis. In the present study, to further understand general molecular changes in sarcoma, patient-derived xenograft (PDX) mouse models of the three most common soft-tissue sarcomas: myxofibrosarcoma, undifferentiated pleomorphic sarcoma (UPS) and liposarcoma were established and the methylation status of histone H3 lysine marks was studied. MATERIALS AND METHODS: Immunoblotting and immunohistochemical staining were used to quantify the extent of methylation of histone H3K4me3 and histone H3K9me3. RESULTS: In all 3 sarcoma types in PDX models, histone H3K4me3 and H3K9me3 were found highly over-methylated compared to normal muscle tissue. CONCLUSION: Histone H3 lysine over-methylation may be a general basis of malignancy of the major sarcoma types.

A rare case of synchronous appendiceal and cecal cancer.

Primary appendiceal cancer is rare, and difficult to diagnose pre-operatively because lack of specific symptoms. This report presents a rare case of synchronous colon and appendiceal cancer. A 50-year-old man was referred to our hospital due to endoscopic submucosal resection (ESD) for early cecal cancer. ESD was performed, and the pathological examination revealed tubular adenocarcinoma with deep submucosal invasion. Laparoscopic ileocecal resection was performed as additional resection after ESD of cecal cancer. There were no obvious abnormalities around the ileocecal region in the preoperative examination. Postoperative pathological examination incidentally revealed a mucosal papillary adenocarcinoma of the appendix, with no residual lesion in the ESD scar. The patient was discharged on the seventh postoperative day. Synchronous appendiceal and colon cancer is extremely rare in past reports. Here, we report the case details and review previous case reports.

Indocyanine Green Fluorescence Image-guided Laparoscopic Hepatectomy Enabled Resection of a Tumor Invisible With Ultrasonography.

BACKGROUND: Ultrasonography (US) is widely used for pre-operative detection of liver tumors. However, US does not have high resolution and very small tumors, tumors located near the liver surface, or those in cirrhotic livers are often not detected. CASE REPORT: A 47-year-old woman with a previous surgery for sigmoid colon cancer (T3N1bM0 Stage3b) showed a liver tumor on the surface of segment 2 by contrast-enhanced computed tomography (CT) and gadoliniumethoxybenzyldiethlenetriaminepen-taacetic acid (Gd-EOB-DTPA) magnetic resonance imaging (MRI). However, preoperative US could not identify a tumor lesion at the same site. The most likely preoperative diagnosis was metastasis from her sigmoid colon cancer and laparoscopic liver resection was performed. Intraoperative ultrasonography (IOUS) did not identify the tumor, but it was visualized with indocyanine green (ICG) fluorescence at the surface of segment 2. Laparoscopic liver resection was performed under fluorescence guidance. Pathological examination showed a pseudotumor with negative margins. CONCLUSION: ICG fluorescence imaging can allow visualization of liver tumors that are undetectable on US.

The Efficacy of Intraoperative Fluorescent Imaging Using Indocyanine Green for Cholangiography During Cholecystectomy and Hepatectomy.

PURPOSE: Bile duct injury is one of the most serious complications of laparoscopic cholecystectomy. Intraoperative indocyanine green (ICG) cholangiography is a safe and useful navigation modality for confirming the biliary anatomy. ICG cholangiography is expected to be a routine method for helping avoid bile duct injuries. PATIENTS AND METHODS: We examined 25 patients who underwent intraoperative cholangiography using ICG fluorescence. Two methods of ICG injection are used: intrabiliary injection (percutaneous transhepatic gallbladder drainage [PTGBD], gallbladder [GB] puncture and endoscopic nasobiliary drainage [ENBD]) at a dosage of 0.025 mg during the operation or intravenous injection with 2.5 mg ICG preoperatively. RESULTS: There were 24 patients who underwent laparoscopic cholecystectomy and 1 patient who underwent hepatectomy. For laparoscopic cholecystectomy, the average operation time was 127 (50-197) minutes, and estimated blood loss was 43.2 (0-400) g. The ICG administration route was intravenous injections in 12 cases and intrabiliary injection in 12 cases (GB injection: 3 cases, PTGBD: 8 cases, ENBD:1 case). The course of the biliary tree was able to be confirmed in all cases that received direct injection into the biliary tract, whereas bile structures were recognizable in only 10 cases (83.3%) with intravenous injection. The postoperative hospital stay was 4.6 (3-9) days, and no postoperative complications (Clavien-Dindo ≧IIIa) were observed. For hepatectomy, a tumor located near the left Glissonian pedicle was resected using a fluorescence image guide. Biliary structures were fluorescent without injury after resecting the tumor. No adverse events due to ICG administration were observed, and the procedure was able to be performed safely. CONCLUSION: ICG fluorescence imaging allows surgeons to visualize the course of the biliary tree in real time during cholecystectomy and hepatectomy. This is considered essential for hepatobiliary surgery to prevent biliary tree injury and ensure safe surgery.

A Novel Color-Coded Liver Metastasis Mouse Model to Distinguish Tumor and Adjacent Liver Segment.

BACKGROUND: It is difficult to distinguish between a tumor and its liver segment with traditional use of indocyanine green (ICG) alone. In the present study, a method was used to limit ICG to the liver segment adjacent to a tumor. A spectrally-distinct fluorescently-labeled tumor-specific antibody against human carcinoembryonic antigen-related cell-adhesion molecules was used to label the metastatic tumor in a patient-derived orthotopic xenograft mouse model to enable color-coded visualization and distinction of a colon-cancer liver metastases and its adjacent liver segment. MATERIALS AND METHODS: Nude mice received surgical orthotopic implantation in the liver of colon-cancer liver metastases derived from two patients. An anti- carcinoembryonic antigen-related cell-adhesion molecules monoclonal antibody (mAb 6G5j) was conjugated to a near-infrared dye IR700DX (6G5j-IR700DX). After three weeks, mice received 6G5j-IR700DX via tail-vein injection 48 hours before surgery. ICG was intravenously injected after ligation of the left or left lateral Glissonean pedicle resulting in labeling of the segment with preserved blood-flow in the liver. Imaging was performed with the Pearl Trilogy and FLARE Imaging Systems. RESULTS: The metastatic liver tumor had a clear fluorescence signal due to selective tumor targeting by 6G5j-IR700DX, which was imaged on the 700 nm channel. The adjacent liver segment, with preserved blood-flow in the liver, had a clear fluorescence ICG 800 nm signal, while the left or left lateral segment had no fluorescence signal. Overlay of the images showed clear color-coded differentiation between the tumor fluorescing at 700 nm and the adjacent liver segment fluorescing at 800 nm. CONCLUSIONS: Color-coding of a liver tumor and uninvolved liver segment has the potential for improved liver resection.

Use of Transumbilical Incision as an Organ Removal Site in Laparoscopic Pancreatectomy.

BACKGROUND/AIM: To evaluate complications and risk factors associated with transumbilical incision as an organ removal site in laparoscopic pancreatectomy (LP). PATIENTS AND METHODS: In total, 52 patients who underwent LP between 2009 and 2017 were included in this study. The development of superficial surgical site infection (SSI) and transumbilical port-site incisional hernia was recorded. RESULTS: None of the patients had SSI. However, three (5.77%) presented with transumbilical incisional hernia. No variables were significantly associated with the risk of transumbilical incisional hernia. CONCLUSION: No evident risk factors correlated with hernia formation. Hence, incisional hernia might have occurred at a certain probability. In some cases, it was caused by technical problems. However, the use of transumbilical incision as an organ removal site was feasible, and a new incision for organ removal alone was not required.