Modulation of prostaglandin transport activity of SLCO2A1 by annexin A2 and S100A10.

Solute carrier organic anion transporter family member 2A1 (SLCO2A1) is a prostaglandin (PG) transporter and serves as the osmosensitive ATP-permeable maxi-anion channel (Maxi-Cl). Since a heterotetrameric complex of annexin A2 (ANXA2) and S100A10 is obligatory for the channel activity, the present study aimed to determine if they regulate SLCO2A1-mediated PG transport. This study examined PGE2 uptake and ATP release in Anxa2 and/or S100a10 knockout (KO) murine breast C127 cells. Deletion of Slco2a1 decreased PGE2-d4 uptake by wild-type (WT) cells in an isotonic medium (290 mosmol/kgH2O). Decreased osmolarity (135 mosmol/kgH2O) stimulated ATP release but did not affect PGE2 uptake kinetics, showing Km (1,280 nM) and Vmax (10.38 pmol/15 s/mg protein) similar to those in isotonic medium (1,227 nM and 10.65 pmol/15 s/mg protein), respectively, in WT cells. Deletion of Anxa2 associated with loss of S100a10 diminished SLCO2A1-mediated ATP release and uncompetitively inhibited PGE2 uptake with lowered Km (376 nM) and Vmax (2.59 pmol/15 s/mg protein). Moreover, the immunoprecipitation assay confirmed the physical interaction of ANXA2 with SLCO2A1 in WT cells. Enforcement of ANXA2 expression to Anxa2 KO cells partially restored PGE2 uptake and increased Km (744.3 nM) and Vmax (9.07 pmol/15 s/mg protein), whereas the uptake clearance (Vmax/Km) did not change much regardless of ANXA2 expression. These results suggest that an ANXA2/S100A10 complex modulates PG transport activity but osmolality has little effect on it; therefore, the bound form of SLCO2A1, which functions as a PG transporter and Maxi-Cl, may exist regardless of changes in the cell volume.NEW & NOTEWORTHY A previous study indicated that the ANXA2/S100A10 complex represents the regulatory component of SLCO2A1-mediated Maxi-Cl channel activity. The present study showed that apparent PGE2 uptake by C127 cells was osmoinsensitive and uncompetitively inhibited by loss of ANXA2 expression, demonstrating that ANXA2 is a regulatory factor of SLCO2A1-mediated PG transport activity.

Combination of high anti-SKI and low anti-TMED5 antibody levels is preferable prognostic factor in esophageal carcinoma.

Given that esophageal cancer is highly malignant, the discovery of novel prognostic markers is eagerly awaited. We performed serological identification of antigens by recombinant cDNA expression cloning (SEREX) and identified SKI proto-oncogene protein and transmembrane p24 trafficking protein 5 (TMED5) as antigens recognized by serum IgG antibodies in patients with esophageal carcinoma. SKI and TMED5 proteins were expressed in Escherichia coli, purified by affinity chromatography, and used as antigens. The serum anti-SKI antibody (s-SKI-Ab) and anti-TMED5 antibody (s-TMED5-Ab) levels were significantly higher in 192 patients with esophageal carcinoma than in 96 healthy donors. The presence of s-SKI-Abs and s-TMED5-Abs in the patients' sera was confirmed by western blotting. Immunohistochemical staining showed that the TMED5 protein was highly expressed in the cytoplasm and nuclear compartments of the esophageal squamous cell carcinoma tissues, whereas the SKI protein was localized predominantly in the nuclei. Regarding the overall survival in 91 patients who underwent radical surgery, the s-SKI-Ab-positive and s-TMED5-Ab-negative statuses were significantly associated with a favorable prognosis. Additionally, the combination of s-SKI-Ab-positive and s-TMED5-Ab-negative cases showed an even clearer difference in overall survival as compared with that of s-SKI-Ab-negative and s-TMED5-Ab-positive cases. The s-SKI-Ab and s-TMED5-Ab biomarkers are useful for diagnosing esophageal carcinoma and distinguishing between favorable and poor prognoses.

Three-year outcomes of preoperative chemoradiotherapy plus nivolumab in microsatellite stable and microsatellite instability-high locally advanced rectal cancer.

BACKGROUND: Preoperative chemoradiotherapy (CRT) followed by surgery is the standard treatment for locally advanced rectal cancer (LARC). We reported the short-term outcomes of the VOLTAGE trial that investigated the safety and efficacy of preoperative CRT followed by nivolumab and surgery. Here, we present the 3-year outcomes of this trial. METHODS: Thirty-nine patients with microsatellite stable (MSS) LARC and five patients with microsatellite instability-high (MSI-H) LARC underwent CRT (50.4 Gy) followed by five doses of nivolumab (240 mg) and surgery. The 3-year relapse-free survival (RFS), overall survival (OS), and associations with biomarkers were evaluated. RESULTS: The 3-year RFS rates in patients with MSS and MSI-H were 79.5% and 100%, respectively, and the 3-year OS rates were 97.4% and 100%, respectively. Of the MSS patients, those with pre-CRT PD-L1 positivity, pre-CRT high CD8 + T cell/effector regulatory T cell (eTreg) ratio, pre-CRT high expression of Ki-67, CTLA-4, and PD-1 had a trend toward better 3-year RFS than those without. CONCLUSIONS: Three-year outcomes of patients with MSI-H were better than those of patients with MSS. PD-L1 positivity, elevated CD8/eTreg ratio, and high expression of Ki-67, CTLA-4, and PD-1 could be positive predictors of prognosis in patients with MSS. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02948348.

Prognostic Relevance of Primary Tumor Sidedness in Early-stage Colorectal Cancer: An Integrated Analysis of 4 Randomized Controlled Trials (JCOG2003A).

OBJECTIVE: The aim of this study was to determine the genuine prognostic relevance of primary tumor sidedness (PTS) in patients with early-stage colorectal cancer (CRC). BACKGROUND: The prognostic relevance of PTS in early-stage CRC remains a topic of debate. Several large epidemiological studies investigated survival only and did not consider the risk of recurrence so far. METHODS: Patients with stage II/III adenocarcinoma of the colon and upper rectum from 4 randomized controlled trials were analyzed. Survival outcomes were compared according to the tumor location: right-sided (cecum to transverse colon) or left-sided (descending colon to upper rectum). RESULTS: A total of 4113 patients were divided into a right-sided group (N=1349) and a left-sided group (N=2764). Relapse-free survival after primary surgery was not associated with PTS in all patients and each stage [hazard ratio (HR) adjusted =1.024 (95% CI: 0.886-1.183) in all patients; 1.327 (0.852-2.067) in stage II; and 0.990 (0.850-1.154) in stage III]. Also, overall survival after primary surgery was not associated with PTS in all patients and each stage [HR adjusted =0.879 (95% CI: 0.726-1.064) in all patients; 1.517 (0.738-3.115) in stage II; and 0.840 (0.689-1.024) in stage III]. In total, 795 patients (right-sided, N=257; left-sided, N=538) developed recurrence after primary surgery. PTS was significantly associated with overall survival after recurrence (HR adjusted =0.773, 95% CI: 0.627-0.954). CONCLUSIONS: PTS had no impact on the risk of recurrence for stage II/III CRC. Treatment stratification based on PTS is unnecessary for early-stage CRC.

Long-term survival and functional outcomes of laparoscopic surgery for clinical stage I ultra-low rectal cancers located within 5 cm of the anal verge: A prospective phase II trial (Ultimate trial).

OBJECTIVE: To clarify the long-term oncological outcomes and postoperative anal, urinary, and sexual functions after laparoscopic surgery for clinical stage I very low rectal carcinoma located near the anal canal. SUMMARY BACKGROUND DATA: Laparoscopic surgery is widely applied for rectal cancer; however, concerns remain, with some studies showing poorer outcomes compared to open surgery. METHODS: This single-arm, phase II trial included patients registered preoperatively from 47 institutions in Japan. The planned sample size was 300. The primary endpoint was the 3-year local recurrence rate. Anal, urinary, and sexual functions were evaluated using a prospective questionnaire. RESULTS: Three-hundred patients were registered between January 2014 and March 2017. Anus-preserving surgery was performed in 278 (93%), including 172 who underwent intersphincteric resection (58%) and 106 (36%) who underwent low anterior resection. The 3-year cumulative local recurrence rate was 6.3%. At 3 years postoperatively, 87% of patients used their own anus, and the median incontinence score improved from 12 at 3 months to 8 at 3 years. Only 5% of patients had severe incontinence (incontinence score of 16 points). Postoperative urinary function evaluation showed that International Prostate Symptom Score and Overactive Bladder Symptom Score decreased 1 week after surgery, but recovered to preoperative level 1 month after surgery. International Consultation on Incontinence Questionnaire-Sort Form remained almost stable after surgery. Sexual function evaluation using the International Index of Erectile Function-5 and International Index of Erectile Function-15 revealed that the patients had deteriorated 3 months after surgery but had recovered only slightly by 6 months. CONCLUSIONS: Laparoscopic surgery achieves feasible long-term oncological outcomes and a high rate of anus preservation with moderate anal function, and an acceptable incontinence score. While urinary function recovered rapidly, sexual function showed poor recovery.

Deep Learning-Based Real-time Ureter Identification in Laparoscopic Colorectal Surgery.

BACKGROUND: Iatrogenic ureteral injury is a serious complication of abdominopelvic surgery. Identifying the ureters intraoperatively is essential to avoid iatrogenic ureteral injury. Here, we developed a model that may minimize this complication. IMPACT OF INNOVATION: We applied a deep learning-based semantic segmentation algorithm to the ureter recognition task and developed a deep learning model called UreterNet. This study aimed to verify whether the ureters could be identified in videos of laparoscopic colorectal surgery. TECHNOLOGY MATERIALS AND METHODS: Semantic segmentation of the ureter area was performed using a convolutional neural network-based approach. Feature Pyramid Networks were used as the convolutional neural network architecture for semantic segmentation. Precision, recall, and the dice coefficient were used as the evaluation metrics in this study. PRELIMINARY RESULTS: We created 14,069 annotated images from 304 videos, with 9537, 2266, and 2266 images in the training, validation, and test datasets, respectively. Concerning ureter recognition performance, precision, recall, and the Dice coefficient for the test data were 0.712, 0.722, and 0.716, respectively. Regarding the real-time performance on recorded videos, it took 71 ms for UreterNet to infer all pixels corresponding to the ureter from a single still image and 143 ms to output and display the inferred results as a segmentation mask on the laparoscopic monitor. CONCLUSIONS AND FUTURE DIRECTIONS: UreterNet is a noninvasive method for identifying the ureter in videos of laparoscopic colorectal surgery and can potentially improve surgical safety. Although this could lead to the development of an image-navigated surgical system, it is necessary to verify whether UreterNet reduces the occurrence of iatrogenic ureteral injury.

Cytological Analysis of the Surgical Field During Transanal Total Mesorectal Excision for Rectal Cancer: A Prospective Study.

BACKGROUND: An unexpectedly large number of patients experienced local recurrence with transanal total mesorectal excision in Norway. This appears to be associated with cancer cell spillage during surgery. OBJECTIVE: To investigate the surgical field cytology during transanal total mesorectal excision. DESIGN: This was a prospective cohort study. SETTINGS: This study was conducted at a single center between June and December 2020. PATIENTS: Forty patients with rectal cancer underwent transanal total mesorectal excision. After irrigation of the surgical field, the water specimens were cytologically evaluated at 6 representative steps. The first sample was used as an initial control. The second, third, fourth, fifth, and sixth samples were collected after the first pursestring suture, rectotomy, the second pursestring suture, specimen resection, and anastomosis, respectively. The clinicopathological features and intraoperative complications of the patients were reviewed. MAIN OUTCOME MEASURES: The primary outcome was to evaluate the presence of cancer cells in washing cytological samples. RESULTS: Of the 40 consecutive patients enrolled in this study, 18 patients underwent neoadjuvant chemoradiotherapy. Incomplete first pursestring suture and rectal perforation were observed in 4 (10.0%) and 3 (7.5%) cases, respectively. In the first sample, 31 patients (77.5%) had malignant cells. Malignant findings were detected in 2 patients (5.0%) from the second to fifth samples. None of the sixth sample exhibited any malignant findings. LIMITATIONS: This single-center study had a small sample size. CONCLUSIONS: Cancer cells were initially detected by cytology, but only a few were observed throughout the procedure; however, cancer cells were not detected in the final surgical field. Further follow-up and novel studies are required to obtain clinically significant findings using cytology during transanal total mesorectal excision. See Video Abstract . ANLISIS CITOLGICO DEL CAMPO QUIRRGICO DURANTE LA ESCISIN TOTAL DEL MESORRECTO TRANSANAL PARA EL CNCER DE RECTO UN ESTUDIO PROSPECTIVO: ANTECEDENTES:Un número inesperadamente grande de pacientes experimentó recurrencia local con la escisión total del mesorrecto transanal en Noruega. Esto parece estar asociado con el derrame de células cancerosas durante la cirugía.OBJETIVO:Investigar la citología del campo quirúrgico durante la escisión total del mesorrecto transanal.DISEÑO:Este fue un estudio de cohorte prospectivo.ENTORNO CLINICO:Este estudio se realizó en un solo centro entre junio y diciembre de 2020.PACIENTES:Cuarenta pacientes con cáncer de recto se sometieron a escisión total del mesorrecto transanal. Después de la irrigación del campo quirúrgico, las muestras de agua se evaluaron citológicamente en seis pasos representativos. La primera muestra se utilizó como control inicial. La segunda, tercera, cuarta, quinta y sexta muestras se recolectaron después de la primera sutura en bolsa de tabaco, la rectotomía, la segunda sutura en bolsa de tabaco, la resección de la muestra y la anastomosis, respectivamente. Se revisaron las características clínico-patológicas y las complicaciones intraoperatorias de los pacientes.PRINCIPALES MEDIDAS DE RESULTADO:El resultado primario fue evaluar la presencia de células cancerosas en el lavado de muestras citológicas.RESULTADOS:De los 40 pacientes consecutivos inscritos en este estudio, 18 pacientes se sometieron a quimiorradioterapia neoadyuvante. Se observaron la primera sutura en bolsa de tabaco incompleta y perforación rectal en cuatro (10,0%) y tres (7,5%) casos, respectivamente. En la primera muestra, 31 (77,5%) pacientes tenían células malignas. Se detectaron hallazgos malignos en dos pacientes (5,0%) de la segunda a la quinta muestra. Ninguno de la sexta muestra demostraron hallazgos malignos.LIMITACIONES:Este estudio unicéntrico tuvo un tamaño de muestra pequeño.CONCLUSIONES:Inicialmente se detectaron células cancerosas mediante citología, pero solo se observaron unas pocas durante todo el procedimiento; sin embargo, no se detectaron células cancerosas en el campo quirúrgico final. Se requieren más seguimientos y estudios novedosos para obtener hallazgos clínicamente significativos mediante citología durante la escisión total del mesorrecto transanal. (Traducción- Dr. Francisco M. Abarca-Rendon ).

Long-term Outcome After Surgical Resection of Paraaortic Lymph Node Metastasis of Colorectal Cancer: A Multicenter Retrospective Study.

BACKGROUND: The significance of resection of paraaortic lymph node metastasis in colorectal cancer is controversial. OBJECTIVE: To clarify the prognosis of colorectal cancer after paraaortic lymph node metastasis resection. DESIGN: Multicenter retrospective study. SETTINGS: Thirty-six institutions in Japan participated in this study. PATIENTS: Patients with resected and pathologically proven paraaortic lymph node metastasis of CRC between 2010 and 2015. DATA SOURCES: Database and medical records at each institution. MAIN OUTCOME MEASURES: Overall survival after paraaortic lymph node metastasis resection, recurrence-free survival, and recurrence patterns after R0 resection of paraaortic lymph node metastasis. RESULTS: A total of 133 patients were included in the primary analysis population in this study. The 5-year overall survival rate (95% confidence interval [CI]) was 41.0% (32.0, 49.8), and the median survival (95% CI) was 4.1 (3.4, 4.7) years. Independent prognostic factors for overall survival were the pathological T stage (pT4 vs. pT1- 3, adjusted hazard ratio [aHR]: 1.91, p = 0.006), other organ metastasis (present vs. absent, aHR: 1.98, p = 0.005), time to metastases (synchronous vs. metachronous, aHR: 2.02, p = 0.02), and number of paraaortic lymph node metastasis (≥3 vs. <3, aHR: 2.13, p = 0.001). The 5-year recurrence-free survival rate (95% CI) was 21.1% (13.5, 29.7), with a median (95% CI) of 1.2 (0.9, 1.4) years. The primary tumor location (left- vs. right-sided colon, aHR: 4.77, p = 0.01; rectum vs. right-sided colon, aHR: 5.27, p = 0.006), other organ metastasis (present vs. absent, aHR: 1.90, p = 0.03), number of paraaortic lymph node metastasis (≥3 vs. <3, aHR: 2.20, p = 0.001), and hospital volume (<10 vs. ≥10, aHR: 2.18, p = 0.02) were identified as independent prognostic factors for recurrence-free survival. Paraaortic lymph node recurrence was the most common at 33.3%. LIMITATIONS: Selection bias cannot be ruled out because of the retrospective nature of the study. CONCLUSIONS: Less than three paraaortic lymph node metastasis was a favorable prognostic factor for both overall survival and recurrence-free survival. However, paraaortic lymph node metastases were considered to be a systemic disease and the significance of resection was limited. See Video Abstract.

Polyandry may mitigate the negative impact of reproductive interference among bumblebees in Japan.

In social hymenopterans, monandry of the queen is an ancestral trait, and polyandry is a derived trait. Polyandry of the queen is the norm in a limited number of lineages, such as honeybees, leaf-cutting ants, Pogonomyrmex ants, and Vespula wasps, which presumably provide fitness advantages for the whole colony. The queen of the introduced bumblebee, Bombus terrestris, is polyandrous in Japan, whereas it is monandrous in native regions. We hypothesize that polyandry can evolve in a process that avoids the negative impacts of reproductive interference caused by interspecific mating and conducted genetic studies of the invasive species B. terrestris and two native subspecies, Bombus hypocrita sapporoensis and Bombus hypocrita hypocrita, in Japan. Our results revealed that although the native queens of B. hypocrita hypocrita allopatric with B. terrestris were strictly monandrous, the native queens of B. hypocrita sapporoensis sympatric with B. terrestris were polyandrous. These results suggested that the queens of native B. hypocrita sapporoensis do not experience negative impacts on interspecific mating from the invasive B. terrestris. We discuss the possibility that reproductive interference is a driving force in selection for multiple mating through an arms race between sympatric species.

Automatic surgical phase recognition-based skill assessment in laparoscopic distal gastrectomy using multicenter videos.

BACKGROUND: Gastric surgery involves numerous surgical phases; however, its steps can be clearly defined. Deep learning-based surgical phase recognition can promote stylization of gastric surgery with applications in automatic surgical skill assessment. This study aimed to develop a deep learning-based surgical phase-recognition model using multicenter videos of laparoscopic distal gastrectomy, and examine the feasibility of automatic surgical skill assessment using the developed model. METHODS: Surgical videos from 20 hospitals were used. Laparoscopic distal gastrectomy was defined and annotated into nine phases and a deep learning-based image classification model was developed for phase recognition. We examined whether the developed model's output, including the number of frames in each phase and the adequacy of the surgical field development during the phase of supra-pancreatic lymphadenectomy, correlated with the manually assigned skill assessment score. RESULTS: The overall accuracy of phase recognition was 88.8%. Regarding surgical skill assessment based on the number of frames during the phases of lymphadenectomy of the left greater curvature and reconstruction, the number of frames in the high-score group were significantly less than those in the low-score group (829 vs. 1,152, P < 0.01; 1,208 vs. 1,586, P = 0.01, respectively). The output score of the adequacy of the surgical field development, which is the developed model's output, was significantly higher in the high-score group than that in the low-score group (0.975 vs. 0.970, P = 0.04). CONCLUSION: The developed model had high accuracy in phase-recognition tasks and has the potential for application in automatic surgical skill assessment systems.

Real-time detection of active bleeding in laparoscopic colectomy using artificial intelligence.

BACKGROUND: Most intraoperative adverse events (iAEs) result from surgeons' errors, and bleeding is the majority of iAEs. Recognizing active bleeding timely is important to ensure safe surgery, and artificial intelligence (AI) has great potential for detecting active bleeding and providing real-time surgical support. This study aimed to develop a real-time AI model to detect active intraoperative bleeding. METHODS: We extracted 27 surgical videos from a nationwide multi-institutional surgical video database in Japan and divided them at the patient level into three sets: training (n = 21), validation (n = 3), and testing (n = 3). We subsequently extracted the bleeding scenes and labeled distinctively active bleeding and blood pooling frame by frame. We used pre-trained YOLOv7_6w and developed a model to learn both active bleeding and blood pooling. The Average Precision at an Intersection over Union threshold of 0.5 (AP.50) for active bleeding and frames per second (FPS) were quantified. In addition, we conducted two 5-point Likert scales (5 = Excellent, 4 = Good, 3 = Fair, 2 = Poor, and 1 = Fail) questionnaires about sensitivity (the sensitivity score) and number of overdetection areas (the overdetection score) to investigate the surgeons' assessment. RESULTS: We annotated 34,117 images of 254 bleeding events. The AP.50 for active bleeding in the developed model was 0.574 and the FPS was 48.5. Twenty surgeons answered two questionnaires, indicating a sensitivity score of 4.92 and an overdetection score of 4.62 for the model. CONCLUSIONS: We developed an AI model to detect active bleeding, achieving real-time processing speed. Our AI model can be used to provide real-time surgical support.

Predictive risk factors for resection surface-related complications after laparoscopic simultaneous resection of primary colorectal tumor and synchronous liver metastases: a single-center retrospective study.

BACKGROUND: Laparoscopic simultaneous resection (LSR) of primary colorectal tumors and synchronous colorectal liver metastases (sCRLM) has been recently performed. This study aimed to evaluate the postoperative outcomes after LSR and determine the risk factors for resection surface-related complications (RSRC), such as postoperative biliary fistula and liver-transection surface abscess. METHODS: Between 2009 and 2022, consecutive patients with sCRLM who underwent LSR were included. We retrospectively analyzed clinicopathological data, including intraoperative factors and postoperative outcomes. The difficulty level of all liver resections was classified according to the IWATE difficulty scoring system (DSS). We then performed univariate and multivariate analyses to identify the risk factors for RSRC. RESULTS: Of the 112 patients, 94 (83.9%) underwent partial hepatectomy and colorectal surgery. The median DSS score was 5 points (1-11), with 12 (10.7%) patients scoring ≥ 7 points. Postoperative complications were observed in 41 (36.6%) patients, of whom 16 (14.3%) experienced severe complications classified as Clavien-Dindo grade IIIa or higher. There was no postoperative mortality. The most common complication was RSRC (19 patients, 17.0%). Multivariate analysis identified American Society of Anesthesiologists (ASA) classification ≥ 3 [odds ratio (OR) 10.3, 95% confidence interval (CI) 1.37-77.8; P = 0.023], DSS score ≥ 7 points (OR 5.08, 95% CI 1.17-20.0; P = 0.030), and right-sided colectomy (OR 4.67, 95% CI 1.46-15.0; P = 0.009) as independent risk factors for RSRC. Postoperative hospital stays were significantly longer for patients with RSRC than for those without RSRC (22 days vs. 11 days; P < 0.001). CONCLUSION: Short-term outcomes of LSR for patients with sCRLM were acceptable in an experienced center. RSRC was the most common complication, and high-difficulty hepatectomy, right-sided colectomy, and ASA classification ≥ 3 were independent risk factors for RSRC.

Deep learning-based vessel automatic recognition for laparoscopic right hemicolectomy.

BACKGROUND: In laparoscopic right hemicolectomy (RHC) for right-sided colon cancer, accurate recognition of the vascular anatomy is required for appropriate lymph node harvesting and safe operative procedures. We aimed to develop a deep learning model that enables the automatic recognition and visualization of major blood vessels in laparoscopic RHC. MATERIALS AND METHODS: This was a single-institution retrospective feasibility study. Semantic segmentation of three vessel areas, including the superior mesenteric vein (SMV), ileocolic artery (ICA), and ileocolic vein (ICV), was performed using the developed deep learning model. The Dice coefficient, recall, and precision were utilized as evaluation metrics to quantify the model performance after fivefold cross-validation. The model was further qualitatively appraised by 13 surgeons, based on a grading rubric to assess its potential for clinical application. RESULTS: In total, 2624 images were extracted from 104 laparoscopic colectomy for right-sided colon cancer videos, and the pixels corresponding to the SMV, ICA, and ICV were manually annotated and utilized as training data. SMV recognition was the most accurate, with all three evaluation metrics having values above 0.75, whereas the recognition accuracy of ICA and ICV ranged from 0.53 to 0.57 for the three evaluation metrics. Additionally, all 13 surgeons gave acceptable ratings for the possibility of clinical application in rubric-based quantitative evaluations. CONCLUSION: We developed a DL-based vessel segmentation model capable of achieving feasible identification and visualization of major blood vessels in association with RHC. This model may be used by surgeons to accomplish reliable navigation of vessel visualization.

Intraoperative artificial intelligence system identifying liver vessels in laparoscopic liver resection: a retrospective experimental study.

BACKGROUND: The precise recognition of liver vessels during liver parenchymal dissection is the crucial technique for laparoscopic liver resection (LLR). This retrospective feasibility study aimed to develop artificial intelligence (AI) models to recognize liver vessels in LLR, and to evaluate their accuracy and real-time performance. METHODS: Images from LLR videos were extracted, and the hepatic veins and Glissonean pedicles were labeled separately. Two AI models were developed to recognize liver vessels: the "2-class model" which recognized both hepatic veins and Glissonean pedicles as equivalent vessels and distinguished them from the background class, and the "3-class model" which recognized them all separately. The Feature Pyramid Network was used as a neural network architecture for both models in their semantic segmentation tasks. The models were evaluated using fivefold cross-validation tests, and the Dice coefficient (DC) was used as an evaluation metric. Ten gastroenterological surgeons also evaluated the models qualitatively through rubric. RESULTS: In total, 2421 frames from 48 video clips were extracted. The mean DC value of the 2-class model was 0.789, with a processing speed of 0.094 s. The mean DC values for the hepatic vein and the Glissonean pedicle in the 3-class model were 0.631 and 0.482, respectively. The average processing time for the 3-class model was 0.097 s. Qualitative evaluation by surgeons revealed that false-negative and false-positive ratings in the 2-class model averaged 4.40 and 3.46, respectively, on a five-point scale, while the false-negative, false-positive, and vessel differentiation ratings in the 3-class model averaged 4.36, 3.44, and 3.28, respectively, on a five-point scale. CONCLUSION: We successfully developed deep-learning models that recognize liver vessels in LLR with high accuracy and sufficient processing speed. These findings suggest the potential of a new real-time automated navigation system for LLR.

Surgical step recognition in laparoscopic distal gastrectomy using artificial intelligence: a proof-of-concept study.

PURPOSE: Laparoscopic distal gastrectomy (LDG) is a difficult procedure for early career surgeons. Artificial intelligence (AI)-based surgical step recognition is crucial for establishing context-aware computer-aided surgery systems. In this study, we aimed to develop an automatic recognition model for LDG using AI and evaluate its performance. METHODS: Patients who underwent LDG at our institution in 2019 were included in this study. Surgical video data were classified into the following nine steps: (1) Port insertion; (2) Lymphadenectomy on the left side of the greater curvature; (3) Lymphadenectomy on the right side of the greater curvature; (4) Division of the duodenum; (5) Lymphadenectomy of the suprapancreatic area; (6) Lymphadenectomy on the lesser curvature; (7) Division of the stomach; (8) Reconstruction; and (9) From reconstruction to completion of surgery. Two gastric surgeons manually assigned all annotation labels. Convolutional neural network (CNN)-based image classification was further employed to identify surgical steps. RESULTS: The dataset comprised 40 LDG videos. Over 1,000,000 frames with annotated labels of the LDG steps were used to train the deep-learning model, with 30 and 10 surgical videos for training and validation, respectively. The classification accuracies of the developed models were precision, 0.88; recall, 0.87; F1 score, 0.88; and overall accuracy, 0.89. The inference speed of the proposed model was 32 ps. CONCLUSION: The developed CNN model automatically recognized the LDG surgical process with relatively high accuracy. Adding more data to this model could provide a fundamental technology that could be used in the development of future surgical instruments.

Hydronephrosis severity as a predictor of postoperative renal function decline following laparoscopic radical nephroureterectomy.

BACKGROUND: This study aimed to investigate factors, including the degree of hydronephrosis, that may be associated with decreased renal function after radical nephroureterectomy (RNU). METHODS: This study included 252 patients who underwent laparoscopic RNU with an estimated glomerular filtration rate (eGFR) ≥ 30 ml/min/1.73 m2 in three institutions. We assessed the association between hydronephrosis grade and perioperative renal function and performed a stepwise multivariate linear regression analysis to identify factors associated with postoperative eGFR. Patients with preoperative eGFR ≥ 50 ml/min/1.73 m2 were divided into a training set and an independent external validation set to develop a predictive model for postoperative renal function. RESULTS: The median preoperative and postoperative eGFR were 61.1 and 46.4 ml/min/1.73 m2, respectively. The eGFR preservation rates were 66.9%, 66.6%, 88.1%, and 100.0% in groups without, with mild, moderate, and severe hydronephrosis, respectively, and this difference was statistically significant (p < 0.001). Multivariate analysis revealed that factors predictive of postoperative eGFR included sex, preoperative eGFR, clinical T stage (cT3-4), and the presence of moderate or severe hydronephrosis. Our predictive model, based on these factors, positively correlated with actual postoperative renal function, and the similarity in categories with or without renal function insufficiency between predicted and actual postoperative renal functions was 78% in both training and validation sets. CONCLUSION: Moderate or severe hydronephrosis is associated with a modest postoperative decline in renal function, while mild hydronephrosis is not. Our predictive model may be useful in predicting postoperative renal function insufficiency and guiding decision-making for perioperative medical treatment.

Changes in TgAb and TPOAb titers are greater in thyrotoxicosis than isolated hypothyroidism induced by PD-1 blockade.

Anti-thyroglobulin antibodies (TgAb) and/or anti-thyroid peroxidase antibodies (TPOAb) positivity at baseline is a risk marker for thyroid immune-related adverse events (thyroid-irAEs) in anti-programmed cell death-1 antibody (PD-1-Ab) treatment; however, it is unknown if TgAb and TPOAb titers are associated with clinical characteristics of thyroid-irAEs. Among 586 patients treated with PD-1-Ab at Nagoya University Hospital between 2 November 2015 and 30 September 2021, 57 patients developed thyroid-irAEs (thyrotoxicosis [n = 38]; hypothyroidism without prior thyrotoxicosis {isolated hypothyroidism} [n = 19]) in whom thyroid function, and TgAb and TPOAb titers were determined at baseline and at the onset. The changes in TgAb (median, 54.8 vs. 0.2 IU/mL; p = 0.002) and TPOAb titers (31.6 vs. 0 IU/mL; p = 0.032) from baseline to onset of developing thyroid-irAEs were greater in patients with thyrotoxicosis than patients with isolated hypothyroidism. Higher TgAb and TPOAb titers, and the TgAb titer at baseline were associated with an earlier onset of thyrotoxicosis and higher peak free thyroxine levels, respectively. Twenty-eight patients who developed hypothyroidism after thyrotoxicosis had higher TgAb (54.5 vs. 10.7 IU/mL; p = 0.011) and TPOAb titers at baseline (46.1 vs. 9.0 IU/mL; p < 0.001) and greater changes in TgAb (61.7 vs. 7.8 IU/mL; p = 0.025) and TPOAb titers (52.8 vs. -0.8 IU/mL; p < 0.001) than patients who did not develop hypothyroidism. The TgAb titer at baseline and changes in the TgAb and TPOAb titers were greater in patients with thyrotoxicosis than patients with isolated hypothyroidism, suggesting that the magnitude of the thyroid autoimmune response reflects the clinical types of thyroid-irAEs.

Development of a laparoscopic sigmoidectomy simulator: Sigmaster.

The sigmoid colon simulator was designed to accurately reproduce the anatomical layer structure and the arrangement of characteristic organs in each layer, and to have conductivity so that energy devices can be used. Dry polyester fibers were used to reproduce the layered structures, which included characteristic blood vessels, nerve sheaths, and intestinal tracts. The adhesive strength of the layers was controlled to allow realistic peeling techniques. The features of the Sigmaster are illustrated through a comparison of simulated sigmoidectomy using Sigmaster and actual surgery. We developed a laparoscopic sigmoidectomy simulator called Sigmaster. Sigmaster is a training device that closely reproduces the membrane structures of the human body and allows surgeons to experience the entire laparoscopic sigmoidectomy process.

Stage-Specific Alteration and Prognostic Relationship of Serum Fumarate Hydratase Autoantibodies in Gastric Cancer.

The relationship between energy production and cancer is attracting attention. This study aimed to investigate the clinicopathological significance of fumarate hydratase (FH), a tricarboxylic acid cycle enzyme, in gastric cancer using autoantibodies as biomarkers. The study analyzed 116 patients who underwent gastric cancer surgery and 96 healthy controls. Preoperative serum FH autoantibody (s-FH-Ab) titers were analyzed using an immunosorbent assay with an amplified luminescent proximity homogeneous assay. Receiver operating characteristic analysis was used to determine the cutoff s-FH-Ab titer. Clinicopathological factors and prognosis were compared between the high and low s-FH-Ab groups. The s-FH-Ab levels were significantly higher in the gastric cancer group than in the control group (p = 0.01). Levels were elevated even in patients with stage I gastric cancer compared with healthy controls (p = 0.02). A low s-FH-Ab level was significantly associated with distant metastasis (p = 0.01), peritoneal dissemination (p < 0.05), and poor overall survival (p < 0.01). Multivariate analysis revealed that low s-FH-Ab levels were an independent risk factor for poor prognosis (p < 0.01). Therefore, s-FH-Ab levels may be a useful biomarker for early diagnosis and the prediction of prognosis in patients with gastric cancer.

JMJD6 Autoantibodies as a Potential Biomarker for Inflammation-Related Diseases.

Inflammation is closely associated with cerebrovascular diseases, cardiovascular diseases, diabetes, and cancers, and it is accompanied by the development of autoantibodies in the early stage of inflammation-related diseases. Hence, it is meaningful to discover novel antibody biomarkers targeting inflammation-related diseases. In this study, Jumonji C-domain-containing 6 (JMJD6) was identified by the serological identification of antigens through recombinant cDNA expression cloning. In particular, JMJD6 is an antigen recognized in serum IgG from patients with unstable angina pectoris (a cardiovascular disease). Then, the serum antibody levels were examined using an amplified luminescent proximity homogeneous assay-linked immunosorbent assay and a purified recombinant JMJD6 protein as an antigen. We observed elevated levels of serum anti-JMJD6 antibodies (s-JMJD6-Abs) in patients with inflammation-related diseases such as ischemic stroke, acute myocardial infarction (AMI), diabetes mellitus (DM), and cancers (including esophageal cancer, EC; gastric cancer; lung cancer; and mammary cancer), compared with the levels in healthy donors. The s-JMJD6-Ab levels were closely associated with some inflammation indicators, such as C-reactive protein and intima-media thickness (an atherosclerosis index). A better postoperative survival status of patients with EC was observed in the JMJD6-Ab-positive group than in the negative group. An immunohistochemical analysis showed that JMJD6 was highly expressed in the inflamed mucosa of esophageal tissues, esophageal carcinoma tissues, and atherosclerotic plaques. Hence, JMJD6 autoantibodies may reflect inflammation, thereby serving as a potential biomarker for diagnosing specific inflammation-related diseases, including stroke, AMI, DM, and cancers, and for prediction of the prognosis in patients with EC.