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.

The anti-TLR4 monoclonal antibody Sa15-21 enhances inflammatory cytokine production in LPS-stimulated macrophages.

Sa15-21, a monoclonal antibody against mouse Toll-like receptor (TLR) 4, can protect mice from lipopolysaccharide (LPS)/D-galactosamine-induced acute lethal hepatitis. Herein, we investigated the molecular mechanisms underlying Sa15-21-mediated regulation of TLR4 signaling in macrophages. Results showed that Sa15-21 enhanced the production of proinflammatory cytokines and attenuated the production of anti-inflammatory cytokines in LPS-stimulated macrophages. Western blotting analysis revealed that Sa15-21 pretreatment had no effect on NF-κB and MAPK signaling in LPS-stimulated macrophages; however, Sa15-21 treatment alone led to a weak and delayed activation of NF-κB and MAPK signaling without any effect on proinflammatory cytokine production. By contrast, Sa15-21 failed to induce the activation of interferon regulatory factor 3. Taken together, our results indicate that Sa15-21 sensitizes macrophages to facilitate the inflammatory response via TLR signaling.

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.

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.

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.

Desmoplastic myxoid tumor, SMARCB1-mutant: a new variant of SMARCB1-deficient tumor of the central nervous system preferentially arising in the pineal region.

Desmoplastic myxoid tumor (DMT), SMARCB1-mutant is a recently proposed brain tumor that occurs in the pineal region of adults. This tumor is characterized by desmoplastic stroma and various degrees of myxoid matrix. Tumor cells with low-grade morphology show polyphenotypic immunoreactivity, and rhabdoid cells are rare. We herein present a case with some uncommon features such as no myxoid stroma and slightly elevated proliferating activity. To date, knowledge on the variety of SMARCB1/INI1-deficient tumors of the central nervous system is gradually increasing, encompassing highly aggressive to slow-growing varieties. DMT, SMARCB1-mutant seems to be relatively benign, but careful attention is necessary because SMARCB1/INI1 deficiency is generally a genetic signature of concern.

Intraoperative Shear Wave Elastography as a Quantitative Predictor of Pancreatic Fibrosis and Exocrine Function.

BACKGROUND/AIM: Soft pancreatic texture is a risk factor for postoperative pancreatic fistula (POPF). However, conventional evaluation of pancreatic texture is largely dependent on subjective assessment and lacks quantitative parameters. The study aimed to use ultrasonic shear wave elastography (SWE) to evaluate pancreatic stiffness to determine if the intraoperative SWE measurement could be a quantitative predictor for POPF. PATIENTS AND METHODS: Fifteen patients scheduled for pancreaticoduodenectomy were included. Both pre- and intra-operative measurement of the pancreatic SWE index (SWEI) were evaluated. Relationships between intraoperative and preoperative SWEI, pathological fibrosis of the resected pancreatic specimen, postoperative exocrine function of the remnant pancreas, and the incidence of POPF were evaluated. RESULTS: The intraoperative SWEI was correlated with the preoperative SWEI, pathological fibrosis of pancreatic tissue, and pancreatic exocrine function. CONCLUSION: Intraoperative SWE measurement of pancreatic elasticity may be useful as a quantitative method for evaluating pancreatic fibrosis and exocrine function.

Laparoscopic Liver Surgery Guided by Virtual Real-time CT-Guided Volume Navigation.

BACKGROUND: Recently, virtual navigation system has been applied to hepatic surgery, enabling better visualization of intrahepatic vascular branches and location of tumor. Intraoperative ultrasonography (IOUS) is the most common form of image guidance during liver surgery. However, during laparoscopic hepatectomies (LH), IOUS has several limitations and its reliability has been poorly evaluated. The objective of this work is to evaluate VRCT (virtual real-time CT-guided volume navigation) during LH. This system aims to provide accurate anatomical orientation for surgeons enhancing the safety of LH. METHODS: Twenty-seven hepatic neoplasms were resected laparoscopically at our institution under reference guidance of VRCT. During operation, electromagnetic tracking of the surgical instrument was used for navigating the direction of accurate liver transection. RESULTS: Twenty-six (96.3%) of the 27 lesions (mean diameter 11 mm) were successfully performed under VRCT guidance. Average registration time was < 2 min. Average setup time was approximately 7 min per procedure. VRCT allows the surgeon to navigate liver transection with acceptable accuracy. The mean error was 12 mm. All surgical margins were negative and the mean histologic resection margin was 9 mm. CONCLUSIONS: VRCT-guided LH is feasible and provides valuable real-time anatomical feedback during hepatic resections. Advancement of such systems to improve accuracy might greatly compensate for the limitation of laparoscopic IOUS.

Preventing clinically relevant pancreatic fistula with combination of linear stapling plus continuous suture of the stump in laparoscopic distal pancreatectomy.

BACKGROUND: Pancreatic fistula is one of the serious complications for patients undergoing distal pancreatectomy, which leads to significant morbidity. The aim of our study is to compare linear stapling closure plus continuous suture with linear stapling closure alone during laparoscopic distal pancreatectomy (LDP) in terms of clinically relevant postoperative pancreatic fistula (POPF) rate. METHODS: Twenty-two patients underwent LDP at our institution between 2011 and 2013. Twelve patients had linear stapling closure with peri-firing compression (LSC) alone compared with ten patients who had linear stapling closure, peri-firing compression plus continuous suture (LSC/CS) for stump closure of remnant pancreas in LDP. Biochemical leak and clinically relevant POPF were compared between both groups. RESULTS: POPF occurred in 4 of 12 (33.3%) patients with linear stapling closure while no patient developed a clinically relevant POPF in the triple combination of linear stapling, peri-firing compression plus continuous suture group (p = 0.043).1 patient (8.3%) in the LSC group and 5 patients (50%) in the LSC/CS group had evidence of a biochemical leak. There were no significant differences in operative time (188.3 vs 187.0 min) and blood loss (135 vs. 240 g) between both groups but there was a significantly of shorter length of hospital stay (11.9 vs. 19.9 days) in LSC/CS group (p = 0.037). There was no mortality in either group. CONCLUSIONS: The triple combination of linear stapling, peri-firing compression plus continuous suture in LDP has effectively prevented occurrence of clinically relevant ISGPF POPF. TRIAL REGISTRATION: The study was retrospectively registered September 30, 2019 at Showa University Ethics Committee as IRB protocol numbers 2943.

Usefulness of a Transumbilical Incision for Organ Removal in Laparoscopic Hepatectomy.

BACKGROUND/AIM: To evaluate the complication rates and risk factors associated with transumbilical wounds and investigate the usefulness of an incision for organ removal in laparoscopic hepatectomy (Lap-H). PATIENTS AND METHODS: We enrolled 42 patients who underwent Lap-H excluding a small partial resection in our hospital between 2013 and 2018. The occurrences of superficial surgical site infection (SSI) and transumbilical port-site incisional hernia were recorded. RESULTS: SSI was not observed, and hernia occurred in 3 patients (7.14%). Univariate analysis revealed that body mass index (BMI) (p=0.004) was significantly associated with the risk of hernia formation. CONCLUSION: High BMI is a risk factor for hernia formation in patients undergoing Lap-H with transumbilical incision; hence, wound closure should be performed carefully. The construction of the transumbilical wound for organ removal was feasible with rationality, with no need to create a new wound.

Corrigendum to "Solid Pseudopapillary Neoplasm of the Pancreas with High-Grade Malignant Transformation Involving p16-RB Pathway Alterations".

[This corrects the article DOI: 10.1155/2020/5980382.].

Laparoscopic Treatment of a Hepatoduodenal Ligament Schwannoma With Infrared Indocyanine Green Fluorescence.

Schwannomas occurring in the hepatoduodenal ligament are extremely rare, with only four cases reported. Here, we describe a case of a 30-mm schwannoma that originated in the hepatoduodenal ligament of a 38-year-old female found during a periodic medical check-up. Magnetic resonance imaging demonstrated a tumor in the hepatoduodenal ligament. Following an ultrasound-guided microbiopsy, histological examination showed solitary fibrous tumor or schwannomas in the liver or originating from the hepαtoduodenal ligament. The relationship between the tumor and associated organs was confirmed intraoperatively, and the tumor was removed safely in its entirety using indocyanine green. The postoperative histopathological examination revealed the presence of a schwannoma with typical characteristics. To our knowledge, this is the first case of hepatoduodenal ligament schwannoma treated by laparoscopic surgery using indocyanine green fluorescence imaging.

Pathological Validity of Using Near-infrared Fluorescence Imaging for Securing Surgical Margins During Liver Resection.

BACKGROUND/AIM: This study investigated the use of near-infrared fluorescent imaging for securing safe margins during liver resection. PATIENTS AND METHODS: This study included 125 patients who underwent liver tumor resection in 2014-2018. Indocyanine green testing was performed 2-14 days before surgery. Histopathological specimens of hepatocellular carcinoma (HCC) and colorectal liver metastasis (CRLM) were evaluated using fluorescent microscopy. RESULTS: Fluorescence microscopy identified signals in 26/53 (49.0%) and 36/72 (50%) cases of HCC and CRLM, respectively. HCC demonstrated total, partial, rim, and combined fluorescence patterns; CRLM uniformly demonstrated rim fluorescence. Although rim fluorescence was seen in both HCC and CRLM, no malignancy was confirmed pathologically in the peritumoral area demonstrating fluorescence. The median widths of fluorescence from the tumor edge in HCC and CRLM were 1227.5 µm and 1608 µm, respectively, with no significant difference. CONCLUSION: Near-infrared fluorescent imaging can reliably detect safe surgical margins intraoperatively during liver resection.

Virtual reality with three-dimensional image guidance of individual patients' vessel anatomy in laparoscopic distal pancreatectomy.

PURPOSE: Three-dimensional virtual endoscopy (3DVE) has the potential advantage of enhanced anatomic delineation and spatial orientation during laparoscopic procedures. In the present study, we aimed to evaluate the impact of 3DVE guidance in laparoscopic distal pancreatectomy (LDP). METHODS: Thirty-eight patients presenting to our hospital with a variety of pancreatic tumors underwent preoperative computed tomography scanning to clearly define the major peripancreatic vasculature and correlate it with a 3DVE system (SYNAPSE VINCENT: Fujifilm Medical, Tokyo, Japan). This map served as the guide during preoperative planning, surgical education, and simulation and as intraoperative navigation reference for LDP. Operative records and pathological findings were analyzed for each procedure. Operative parameters were compared between the 38 patients in this study and 8 patients performed without 3DVE guidance at our institution. RESULTS: The 3DVE navigation system successfully created a preoperative resection map in all patients. Relevant peripancreatic vasculature displayed on the system was identified and compared during the intervention. The mean blood loss in LDP performed under 3DVE guidance versus LDP without 3DVE was 168.5 +/- 347.6 g versus 330.0 +/- 211.4 g, p = 0.008 while and the operative time was 171.9 +/- 51.7 min versus 240.6 +/- 24.8 min, p = 0.001. CONCLUSIONS: 3DVE in conjunction with a "laparoscopic eye" creates a preoperative and intraoperative three-dimensional data platform that potentially enhances the accuracy and safety of LDP.

Malignant transformation of a dysembryoplastic neuroepithelial tumor verified by a shared copy number gain of the tyrosine kinase domain of FGFR1.

Dysembryoplastic neuroepithelial tumors (DNTs) are regarded as benign glioneuronal neoplasms because of their excellent outcomes; however, rare DNTs show malignant transformation. We herein described a case of DNT showing malignant transformation. The patient had intractable epilepsy caused by a tumor at 1 year of age and partial resection was performed. After surgery, the residual tumor showed regrowth and surgery was performed again at 4 years of age. The resected tumor showed the typical histological features of DNT, such as specific glioneuronal elements and alveolar structures. Tumor regrowth was detected again at 6 years of age, and the patient underwent gross total resection. Histologically, the tumor was composed of a high-grade glial component mixed with atypical neuronal cells, and the diagnosis of an anaplastic glioneuronal tumor was made. Genetically, DNT and the anaplastic glioneuronal tumor both shared a copy number gain of the tyrosine kinase domain of fibroblast growth factor receptor 1 (FGFR1), as demonstrated by multiplex ligation-dependent probe amplification (MLPA), corresponding to internal tandem duplication (ITD). A frequent FGFR1-ITD in DNT was previously reported. To the best of our knowledge, an identical mutation between primary and transformed DNT has not yet been demonstrated by MLPA.

Solid Pseudopapillary Neoplasm of the Pancreas with High-Grade Malignant Transformation Involving p16-RB Pathway Alterations.

Solid pseudopapillary neoplasm (SPN) of the pancreas has generally been regarded as a low-grade malignant tumour that preferentially develops in young women and can have a good prognosis with surgery. Among the few patients who have died from metastatic SPN are mostly those whose tumours harbour an undifferentiated component characterized by diffuse sheets of cells with increased nuclear atypia and proliferative index. We herein report a case of an aggressive, fatal, solid pseudopapillary neoplasm (SPN) of the pancreas in a 63-year-old woman complaining of epigastric pain. Despite having undergone surgical resection for a 10 cm pancreatic mass and multiple liver metastases, the patient later died due to uncontrollable metastases 36 months after the initial surgery. Histological examination showed that the tumour displayed unusual high-grade malignant features, showing diffuse sheets of cells with increased nuclear atypia and proliferative activity, along with conventional low-grade malignant features. The tumour was subsequently recognized as an SPN with foci of high-grade malignant transformation according to the 2010 World Health Organization classification. Immunohistochemical studies revealed that p16-RB pathway alterations contributed to the high-grade malignant transformation. The present case report suggests the necessity for developing diagnostic and treatment methods targeting p16 and RB for high-grade variants of SPN.

Oligodendroglioma showing pleomorphic xanthoastrocytoma-like perivascular microlesion: With IDH1, TERT promoter mutation and 1p/19q codeletion detected in both components.

We report a histological and genetic study of concurrent oligodendroglioma and a microscopic pleomorphic xanthoastrocytoma (PXA)-like lesion in a 48-year-old male. He presented with generalized seizure, and magnetic resonance imaging revealed a nonenhanced left frontal lobe mass suggesting low-grade glioma. The patient underwent craniotomy and tumor resection. Histopathological examination of the surgical specimen showed an oligodendroglioma with a PXA-like element; the latter measured 0.9 mm and occupied a Virchow-Robin space of the superficial cortex. The whole tumor had no elevated mitotic activity, microvascular proliferation or necrosis. Each component was immunohistochemically isocitrate dehydrogenase (IDH1)-R132H positive, p53 negative and ATRX positive. Genetic analyses clarified identical IDH1 G395A mutation, promoter C228T mutation and 1p/19q codeletion in both elements. Careful integration of histology and telomerase reverse transcriptase (TERT) molecular parameters revealed that this case was an oligodendroglioma showing PXA-like features, rather than a collision tumor. This case provides further insights into the gliomagenesis.