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.

Overexpression of VSNL1 Enhances Cell Proliferation in Colorectal Carcinogenesis.

INTRODUCTION: We have previously reported that overexpression of visinin-like protein 1 (VSNL1) is frequently observed in advanced colorectal adenocarcinomas and correlates with poorer prognosis. In this study, we determined the levels of VSNL1 expression in the earlier stages of colorectal tumors including adenomas and adenocarcinomas, and attempted to clarify the functional significance of VSNL1 overexpression in colorectal carcinogenesis. METHODS: Levels of VSNL expression in colorectal tumor tissues were analyzed using immunohistochemistry. The effects of VSNL1 downregulation and overexpression on cell proliferation, resistance to apoptosis, and invasiveness were determined using two VSNL1-overexpressing colorectal cancer cell lines, CW-2 and HCT-116 and VSNL1 inducibly expressing SNU-C5, respectively. Gene expression signatures in VSNL1-downregulated CW-2 and HCT-116 were identified using transcriptome and gene set enrichment analyses. RESULTS: VSNL1 expression was restricted to only a few crypt cells in the non-tumorous epithelium, whereas it became enhanced in adenomas and adenocarcinomas with the progression of tumorigenesis. Downregulation of VSNL1 in CW-2 and HCT-116 cells suppressed their proliferation through induction of apoptosis. Conversely, overexpression of VSNL1 in SNU-C5 cells enhanced resistance to anoikis. Transcriptome and gene set enrichment analyses revealed that downregulation of VSNL1 altered the expression level of the apoptosis-related gene set in CW-2 and HCT-116 cells. CONCLUSION: VSNL1 plays a role in both the development and progression of colorectal tumors by enhancing cell viability.

Impact of the endoscopic surgical skill qualification system on conversion to laparotomy after low anterior resection for rectal cancer in Japan (a secondary analysis of the EnSSURE study).

BACKGROUND AND AIMS: Conversion to laparotomy is among the serious intraoperative complications and carries an increased risk of postoperative complications. In this cohort study, we investigated whether or not the Endoscopic Surgical Skill Qualification System (ESSQS) affects the conversion rate among patients undergoing laparoscopic surgery for rectal cancer. METHODS: We performed a retrospective secondary analysis of data collected from patients undergoing laparoscopic surgery for cStage II and III rectal cancer from 2014 to 2016 across 56 institutions affiliated with the Japan Society of Laparoscopic Colorectal Surgery. Data from the original EnSSURE study were analyzed to investigate risk factors for conversion to laparotomy by performing univariate and multivariate analyses based on the reason for conversion. RESULTS: Data were collected for 3,168 cases, including 65 (2.1%) involving conversion to laparotomy. Indicated conversion accounted for 27 cases (0.9%), while technical conversion accounted for 35 cases (1.1%). The multivariate analysis identified the following independent risk factors for indicated conversion to laparotomy: tumor diameter [mm] (odds ratio [OR] 1.01, 95% confidence interval [CI] 1.01-1.05, p = 0.0002), combined resection of adjacent organs [+/-] (OR 7.92, 95% CI 3.14-19.97, p < 0.0001), and surgical participation of an ESSQS-certified physician [-/+] (OR 4.46, 95% CI 2.01-9.90, p = 0.0002). The multivariate analysis identified the following risk factors for technical conversion to laparotomy: registered case number of institution (OR 0.99, 95% CI 0.99-1.00, p = 0.0029), institution type [non-university/university hospital] (OR 3.52, 95% CI 1.54-8.04, p = 0.0028), combined resection of adjacent organs [+/-] (OR 5.96, 95% CI 2.15-16.53, p = 0.0006), and surgical participation of an ESSQS-certified physician [-/+] (OR 6.26, 95% CI 3.01-13.05, p < 0.0001). CONCLUSIONS: Participation of ESSQS-certified physicians may reduce the risk of both indicated and technical conversion. Referral to specialized institutions, such as high-volume centers and university hospitals, especially for patients exhibiting relevant background risk factors, may reduce the risk of conversion to laparotomy and lead to better outcomes for patients. TRIAL REGISTRATION: This study was registered with the Japanese Clinical Trials Registry as UMIN000040645.

Efficacy of pancreaticojejunostomy of the pancreatic stump during distal or central pancreatectomy.

BACKGROUND: A stapler is usually used for transection and closure of the pancreas in distal pancreatectomy (DP) or central pancreatectomy (CP). When the pancreas is transected to the right of the portal vein, it is difficult to use a stapler and clinically relevant postoperative pancreatic fistula (CR-POPF) frequently occurs. We report on the efficacy of pancreaticojejunostomy (PJ) of the pancreatic stump for patients in whom stapler use is difficult. METHODS: Patients who underwent DP or CP were enrolled in this study. The pancreas was usually transected by a stapler, and ultrasonic coagulating shears (UCS) were used depending on the tumor situation. When using UCS, hand-sewn closure or PJ was performed for the pancreatic stump. The relationship between clinicopathological factors and the methods of pancreatic transection and closure were investigated. RESULTS: In total, 164 patients underwent DP or CP, and the pancreas was transected with a stapler in 150 patients and UCS in 14 patients. The rate of CR-POPF was higher and the postoperative hospital stay was longer in the UCS group than in the stapler group. PJ of the pancreatic stump, which was performed for 7 patients, did not worsen intraoperative factors. CR-POPF was not seen in these 7 patients, which was significantly less than that with hand-sewn closure. CONCLUSIONS: PJ of the pancreatic stump during DP or CP reduces CR-POPF compared with hand-sewn closure and may be useful especially when the pancreas is transected to the right of the portal vein.

Clinical significance of colonoscopy before laparoscopic bariatric/metabolic surgery in Japanese patients.

PURPOSE: Obesity is known to be associated with colorectal adenoma (CRA) and colorectal cancer (CRC); yet colonoscopy is not considered an essential preoperative evaluation before bariatric/metabolic surgery. The aim of this study was to clarify the clinical significance of preoperative colonoscopy for obese Japanese patients. METHODS: The subjects of this retrospective study were 114 patients who underwent screening colonoscopy before bariatric/metabolic surgery. Multivariate analyses were performed to evaluate the independent predictors of CRA/CRC among the characteristics identified as significant or nearly significant by univariate analyses. RESULTS: Colonoscopy revealed abnormal findings indicating the need for biopsy or polypectomy in 20 of the 114 patients (17.5%), and CRA was diagnosed in 13 patients (11.4%). Three patients (2.6%), who were all ≥ 56 years old, had a CRA ≥ 10 mm in diameter. The multivariate analysis showed that older age and male sex were significant predictors of CRA/CRC, which was identified in 46.2% of the male patients aged ≥ 46 years. CONCLUSION: Our findings suggest that older age and male sex may be risk factors for CRA/CRC in obese Japanese candidates for bariatric/metabolic surgery; thus, preoperative colonoscopy should be considered for these high-risk patients.

Risk factors for anastomotic leakage after low anterior resection for obese patients with rectal cancer.

PURPOSE: We aimed to analyze the risk factors for anastomotic leakage (AL) after low anterior resection (LAR) in obese patients (body mass index [BMI] ≥ 25 kg/m2) with rectal cancer. METHODS: Data were collected from four hundred two obese patients who underwent LAR for rectal cancer in 51 institutions. RESULTS: Forty-six (11.4%) patients had clinical AL. The median BMI (27 kg/m2) did not differ between the AL and non-AL groups. In the AL group, comorbid respiratory disease was more common (p = 0.025), and the median tumor size was larger (p = 0.002). The incidence of AL was 11.5% in the open surgery subgroup and 11.4% in the laparoscopic surgery subgroup. Among the patients who underwent open surgery, the AL group showed a male predominance (p = 0.04) in the univariate analysis, but it was not statistically significant in the multivariate analysis. Among the patients who underwent laparoscopic surgery, the AL group included a higher proportion of patients with comorbid respiratory disease (p = 0.003) and larger tumors (p = 0.007). CONCLUSION: Comorbid respiratory disease and tumor size were risk factors for AL in obese patients with rectal cancer. Careful perioperative respiratory management and appropriate selection of surgical procedures are required for obese rectal cancer patients with respiratory diseases.

Current status and issues regarding surgical education in the region: a questionnaire survey in Oita prefecture in Japan.

BACKGROUND: The shortage and aging of surgeons in regional surgical care has been remarkable, and the importance of surgical education for young surgeons in the region is only increasing. However, there are very few reports about regional surgical education. This study aimed to clarify the current status and issues regarding surgical education in regional surgical care and to examine the ideal way to provide surgical education in the region. METHODS: Two questionnaire surveys were carried out. (1) "Survey on the awareness regarding the education of young surgeons" was conducted by mail in institutions where surgeons worked. (2) "Survey on the current status of surgical education for young surgeons" was conducted via the Internet with surgeons under 40 years old and mentors at the same facility. RESULTS: There were 175 respondents to survey (1), among whom 131 (75%) surgeons were interested in educating young surgeons, and 112 (64%) were actively participating in this educating. Regarding the best evaluation methods for mentors who are educating young surgeons, the most frequent answer was "I don't know (51%)". The number of respondents in survey (2) was 87, including 27 (31%) young surgeons and 60 (69%) mentors. Although there was no difference between young surgeons and mentors in the level of satisfaction with the current status of young surgeons, 37% of young surgeons in urban areas were dissatisfied with their current status, compared to 0% in the regional area (p < 0.05). CONCLUSIONS: Although surgeons did not have confidence in their own education, the level of satisfaction among young surgeons was high even in those providing regional surgical care. Development of an evaluation system for surgical education is necessary for young surgeons to receive more effective surgical education in the region.

Efficacy of cooling therapy and α-lipoic acid derivative against chemotherapy-induced alopecia in an animal model.

Chemotherapy-induced alopecia is frequently induced by various regimens of chemotherapy and has a significant impact on mental health and quality of life. However, the effect of available current treatment for chemotherapy-induced alopecia is not sufficient. This study aimed to clarify the therapeutic effects and mechanism of skin cooling and the antioxidant α-lipoic acid derivative on chemotherapy-induced alopecia. We developed a chemotherapy-induced alopecia model of cyclophosphamide (120 µg/g) using Institute of Cancer Research mice. We used cooling therapy and α-lipoic acid derivative application as the treatments. We compared the alopecia score, hair bulb diameter, insulin-like growth factor-1 level, vascular permeability, and apoptosis between the control and treatment groups. The alopecia score significantly improved in each treatment group compared with that in the cyclophosphamide group. Hair bulb diameter significantly improved in the cyclophosphamide + cooling group compared with that in the cyclophosphamide group. The insulin-like growth factor-1 level and vascular permeability level was significantly retained and suppressed, respectively, in each treatment group compared with that in the cyclophosphamide group. The number of apoptotic cells in the vascular endothelium significantly decreased in the cyclophosphamide + α-lipoic acid derivative group compared with that in the cyclophosphamide group. In conclusion, cooling therapy and α-lipoic acid derivative facilitated recovery from chemotherapy-induced alopecia caused by cyclophosphamide through decreasing vascular permeability.

Association of immune-related expression profile with sensitivity to chemotherapy in esophageal squamous cell carcinoma.

Neoadjuvant chemotherapy (NAC) followed by surgery is one of the standard therapeutic approaches in Japan for patients with locally advanced esophageal carcinoma. Recently, the JCOG1109 study revealed that NAC with docetaxel, cisplatin and 5-fluorouracil (5-FU) (DCF-NAC) is superior to NAC with cisplatin and 5-FU, and has now become the standard preoperative chemotherapy. Using a microarray system, we have previously investigated the expression profiles of endoscopic biopsy samples from patients with esophageal squamous cell carcinoma (ESCC) before DCF-NAC (preNAC) and identified 17 molecules as biomarkers predictive of a pathologically complete response to DCF-NAC. Here, we re-grouped our previous dataset based on the histopathological response grade with the addition of several microarray profiles and conducted a re-analysis using bioinformatic web tools including DAVID, GSEA, UALCAN, and CIBERSORTx. We identified 204 genes that were differentially expressed between the highly resistant and sensitive groups. Some of these differentially expressed genes (DEGs) were related to the immune response and showed higher expression in the sensitive group. UALCAN showed that high expression of 28 of the top 50 DEGs was associated with a favorable prognosis (p < 0.25), and that this reached a significant (p < 0.05) level for 18 of them, suggesting that patients with high expression of these genes might have benefited from chemotherapy and thus had a better outcome. In preNAC biopsy tissues from a DCF-sensitive case, we demonstrated the presence of cells expressing mRNA for CXCL9, one of the prognosis-related DEGs. Our results highlight the association of immune-related expression profile in preNAC ESCC with the DCF-NAC efficacy.

Involvement of clusterin expression in the refractory response of pancreatic cancer cells to a MEK inhibitor.

Constitutive activation of the mitogen-activated protein kinase (MAPK) signaling pathway is essential for tumorigenesis of pancreatic ductal adenocarcinoma (PDAC). To date, however, almost all clinical trials of inhibitor targeting this pathway have failed to improve the outcome of patients with PDAC. We found that implanted MIA Paca2, a human PDAC cell line sensitive to a MAPK inhibitor, PD0325901, became refractory within a week after treatment. By comparing the expression profiles of MIA Paca2 before and after acquisition of the refractoriness to PD0325901, we identified clusterin (CLU) as a candidate gene involved. CLU was shown to be induced immediately after treatment with PD0325901 or expressed primarily in more than half of PDAC cell lines, enhancing cell viability by escaping from apoptosis. A combination of PD0325901 and CLU downregulation was found to synergistically or additively reduce the proliferation of PDAC cells. In surgically resected PDAC tissues, overexpression of CLU in cancer cells was observed immunohistochemically in approximately half of the cases studied. Collectively, our findings highlight the mechanisms responsible for the rapid refractory response to MEK inhibitor in PDAC cells, suggesting a novel therapeutic strategy that could be applicable to patients with PDAC using inhibitor targeting the MAPK signaling pathway and CLU.

A Prospective Multicenter Phase II Trial of Neoadjuvant Chemotherapy with Gemcitabine Plus Nab-Paclitaxel for Borderline Resectable Pancreatic Cancer with Arterial Involvement.

BACKGROUND: Only two clinical trials have shown the effects of neoadjuvant treatment for borderline resectable pancreatic cancer with arterial involvement (BRPC-A). Here, we aimed to analyze the efficacy and safety of neoadjuvant gemcitabine plus nab-paclitaxel (GnP) for BRPC-A. PATIENTS AND METHODS: A prospective, single-arm, multicenter phase II trial was conducted. Patients who were radiologically and histologically diagnosed with BRPC-A were enrolled. A central review was conducted to confirm the presence of BRPC-A. Patients received two to four cycles of GnP before surgery. The primary endpoint of the study was the R0 resection rate. Overall survival (OS) was evaluated in an ancillary study. RESULTS: Thirty-five patients were enrolled, of whom 33 were subjected to central review and 28 were confirmed to have BRPC-A. All eligible patients with BRPC-A received neoadjuvant GnP. Nineteen patients underwent pancreatic resections. Postoperative complications of Clavien-Dindo IIIa or lower were observed in 11 patients. No treatment-related mortalities were observed. R0 resection was achieved in 17 patients (89%); the R0 resection rate was 61% in eligible patients. One patient underwent curative resection after termination of the treatment protocol, resulting in an overall R0 resection rate of 64%. The median overall survival (OS) and 2-year OS rate were 24.9 months [95% confidence interval (CI) 19.0 months to not estimatable] and 53.6%, respectively. OS in patients with BRPC-A who achieved overall R0 resection was significantly longer than that in the other patients (p = 0.0255). CONCLUSIONS: Neoadjuvant GnP is a safe and effective strategy for BRPC-A, providing a chance for curative resection and improved survival.

Specialty-Certified Colorectal Surgeons Demonstrate Favorable Short-term Surgical Outcomes for Laparoscopic Low Anterior Resection: Assessment of a Japanese Nationwide Database.

BACKGROUND: There are few studies on the impact of a colorectal-specific technically certified surgeon on good surgical outcomes for laparoscopic low anterior resection in the real world. OBJECTIVE: To evaluate the short-term outcomes of laparoscopic low anterior resection with the participation of a certified colorectal surgeon. DESIGN: This was a retrospective cohort study using a Japanese nationwide database. SETTING: This study was conducted as a project for the Japan Society of Endoscopic Surgery and the Japanese Society of Gastroenterological Surgery. PATIENTS: This study included 41,741 patients listed in the National Clinical Database who underwent laparoscopic low anterior resection performed by certified, noncertified, and colorectal-specific certified surgeons, according to the Endoscopic Surgical Skill Qualification System, from 2016 to 2018. MAIN OUTCOME MEASURES: Operative mortality rate and anastomotic leak rate were the primary outcome measures. RESULTS: Overall 30-day mortality and operative mortality were 0.2% and 0.3%, respectively, without significant differences between all kinds of certified and noncertified surgeon groups. Overall anastomotic leak rate was 9.3%, with a significant difference between the 2 groups. Colorectal- and stomach-certified groups had lower 30-day mortality and operative mortality than the biliary-certified and noncertified groups. The anastomotic leak rate was the lowest in the colorectal-certified group. Based on a logistic regression analysis using the risk-adjusted model, operative mortality was significantly higher in the biliary-certified group than in the colorectal-certified group. Moreover, anastomotic leak rate was significantly lower in the colorectal-certified group than in the stomach-certified and noncertified groups. LIMITATIONS: This study was a retrospective study, and there was a possibility of different definitions of anastomotic leak due to the use of a nationwide database. CONCLUSIONS: The participation of a colorectal-specific certified surgeon may decrease the risk of operative mortality and anastomotic leak for laparoscopic low anterior resection. CIRUJANO COLORRECTAL ALTAMENTE CALIFICADO PROVOCA RESULTADOS QUIRRGICOS FAVORABLES A CORTO PLAZO PARA LA RESECCIN ANTERIOR BAJA LAPAROSCPICA EVALUACIN DE LA BASE DE DATOS NACIONAL JAPONESA: ANTECEDENTES:Hay pocos estudios sobre el impacto de un cirujano certificado técnicamente especializado en cáncer colorrectal con un buen resultado quirúrgico para la resección anterior baja laparoscópica en el mundo real.OBJETIVO:Evaluar los resultados a corto plazo de la resección anterior baja laparoscópica con la participación de un cirujano colorrectal certificado.DISEÑO:Este fue un estudio de cohorte retrospectivo que utilizó una base de datos nacional japonesa.AJUSTE:Este estudio se realizó como un proyecto para la Sociedad Japonesa de Cirugía Endoscópica y la Sociedad Japonesa de Cirugía Gastroenterológica.PACIENTES:este estudio incluyó a 41 741 pacientes incluidos en la base de datos clínica nacional que se sometieron a una resección anterior baja laparoscópica realizada por cirujanos certificados, no certificados y certificados específicamente colorrectales, según el Sistema de calificación de habilidades quirúrgicas endoscópicas de 2016 a 2018.PRINCIPALES MEDIDAS DE RESULTADO:La tasa de mortalidad operatoria y la tasa de fuga anastomótica fueron los resultados primarios.RESULTADOS:La mortalidad general a los 30 días y la mortalidad operatoria fueron del 0,2 % y el 0,3 %, respectivamente, sin diferencias significativas entre los grupos de todos los tipos de cirujanos certificados y no certificados. La tasa global de fuga anastomótica fue del 9,3 %, con una diferencia significativa entre los dos grupos. Los grupos con certificación colorrectal y estomacal tuvieron una mortalidad a los 30 días y una mortalidad operatoria más bajas que los grupos con certificación biliar y sin certificación. La tasa de fuga anastomótica fue la más baja en el grupo certificado colorrectal. Con base en un análisis de regresión logística utilizando el modelo ajustado por riesgo, la mortalidad operatoria fue significativamente más alta en el grupo con certificación biliar que en el grupo con certificación colorrectal. Además, la tasa de fuga anastomótica fue significativamente más baja en el grupo con certificación colorrectal que en los grupos con certificación estomacal y sin certificación.LIMITACIONES:Este estudio fue retrospectivo y existía la posibilidad de diferentes definiciones de fuga anastomótica debido al uso de una base de datos nacional.CONCLUSIONES:La participación de un cirujano certificado en video específico colorrectal puede disminuir el riesgo de mortalidad operatoria y fuga anastomótica para la resección anterior baja laparoscópica. (Traducción-Dr. Mauricio Santamaria ).

Glucose metabolic upregulation via phosphorylation of S6 ribosomal protein affects tumor progression in distal cholangiocarcinoma.

BACKGROUND: The prognosis of distal cholangiocarcinoma (dCCA) remains poor; thus, the identification of new therapeutic targets is warranted. Phosphorylated S6 ribosomal protein indicates a mammalian target of rapamycin complex 1 (mTORC1) activity, and mTORC1 plays a central role in controlling cell growth and regulating glucose metabolism. We aimed to clarify the effect of S6 phosphorylation on tumor progression and the glucose metabolic pathway in dCCA. METHODS: Thirty-nine patients with dCCA who underwent curative resection were enrolled in this study. S6 phosphorylation and the expression of GLUT1 were evaluated by immunohistochemistry, and their relationship with clinical factors was investigated. The effect of S6 phosphorylation on glucose metabolism with PF-04691502 treatment, an inhibitor of S6 phosphorylation, was examined in cancer cell lines by Western blotting and metabolomics analysis. Cell proliferation assays were performed with PF-04691502. RESULTS: S6 phosphorylation and the expression of GLUT1 were significantly higher in patients with an advanced pathological stage. Significant correlations between GLUT1 expression, S6 phosphorylation, and SUV-max of FDG-PET were shown. In addition, cell lines with high S6 phosphorylation levels showed high GLUT1 levels, and the inhibition of S6 phosphorylation reduced the expression of GLUT1 on Western blotting. Metabolic analysis revealed that inhibition of S6 phosphorylation suppressed pathways of glycolysis and the TCA cycle in cell lines, and then, cell proliferation was effectively reduced by PF-04691502. CONCLUSION: Upregulation of glucose metabolism via phosphorylation of S6 ribosomal protein appeared to play a role in tumor progression in dCCA. mTORC1 may be a therapeutic target for dCCA.

Skill-qualified surgeons positively affect short-term outcomes after laparoscopic gastrectomy for gastric cancer: a survey of the National Clinical Database of Japan.

BACKGROUND: Proficiency of the operating surgeon is one of the most critical factors potentially associated with reductions in complications and surgery-related mortality. With video-rating systems having shown potential for assessing laparoscopic surgeons' proficiency, the Endoscopic Surgical Skill Qualification System (ESSQS) was developed by the Japan Society for Endoscopic Surgery to subjectively assess the proficiency of laparoscopic surgeons by rating applicants' non-edited case videos. We conducted a study to evaluate how ESSQS skill-qualified (SQ) surgeon involvement influences short-term outcomes of laparoscopic gastrectomy performed for gastric cancer. METHODS: Data from the National Clinical Database regarding laparoscopic distal and total gastrectomy performed for gastric cancer between January 2016 and December 2018 were analyzed. Operative mortality, defined as 30-day mortality or 90-day in-hospital mortality, and anastomotic leakage rates were compared per involvement vs. non-involvement of an SQ surgeon. Outcomes were also compared per involvement of a gastrectomy-, colectomy-, or cholecystectomy-qualified surgeon. The association between the area of qualification and operative mortality/anastomotic leakage was also analyzed with a generalized estimating equation logistic regression model used to account for patient-level risk factors and institutional differences. RESULTS: Of 104,093 laparoscopic distal gastrectomies, 52,143 were suitable for inclusion in the study; 30,366 (58.2%) were performed by an SQ surgeon. Of 43,978 laparoscopic total gastrectomies, 10,326 were suitable for inclusion; 6501 (63.0%) were performed by an SQ surgeon. Gastrectomy-qualified surgeons outperformed non-SQ surgeons in terms of both operative mortality and anastomotic leakage. They also outperformed cholecystectomy- and colectomy-qualified surgeons in terms of operative mortality or anastomotic leakage in distal and total gastrectomy, respectively. CONCLUSION: The ESSQS appears to discriminate laparoscopic surgeons who can be expected to achieve significantly improved gastrectomy outcomes.

Universal meta-competencies of operative performances: a literature review and qualitative synthesis.

BACKGROUND: Prioritizing patient health is essential, and given the risk of mortality, surgical techniques should be objectively evaluated. However, there is no comprehensive cross-disciplinary system that evaluates skills across all aspects among surgeons of varying levels. Therefore, this study aimed to uncover universal surgical competencies by decomposing and reconstructing specific descriptions in operative performance assessment tools, as the basis of building automated evaluation system using computer vision and machine learning-based analysis. METHODS: The study participants were primarily expert surgeons in the gastrointestinal surgery field and the methodology comprised data collection, thematic analysis, and validation. For the data collection, participants identified global operative performance assessment tools according to detailed inclusion and exclusion criteria. Thereafter, thematic analysis was used to conduct detailed analyses of the descriptions in the tools where specific rules were coded, integrated, and discussed to obtain high-level concepts, namely, "Skill meta-competencies." "Skill meta-competencies" was recategorized for data validation and reliability assurance. Nine assessment tools were selected based on participant criteria. RESULTS: In total, 189 types of skill performances were extracted from the nine tool descriptions and organized into the following five competencies: (1) Tissue handling, (2) Psychomotor skill, (3) Efficiency, (4) Dissection quality, and (5) Exposure quality. The evolutionary importance of these competences' different evaluation targets and purpose over time were assessed; the results showed relatively high reliability, indicating that the categorization was reproducible. The inclusion of basic (tissue handling, psychomotor skill, and efficiency) and advanced (dissection quality and exposure quality) skills in these competencies enhanced the tools' comprehensiveness. CONCLUSIONS: The competencies identified to help surgeons formalize and implement tacit knowledge of operative performance are highly reproducible. These results can be used to form the basis of an automated skill evaluation system and help surgeons improve the provision of care and training, consequently, improving patient prognosis.

Impact of AI system on recognition for anatomical landmarks related to reducing bile duct injury during laparoscopic cholecystectomy.

BACKGROUND: According to the National Clinical Database of Japan, the incidence of bile duct injury (BDI) during laparoscopic cholecystectomy has hovered around 0.4% for the last 10 years and has not declined. On the other hand, it has been found that about 60% of BDI occurrences are due to misidentifying anatomical landmarks. However, the authors developed an artificial intelligence (AI) system that gave intraoperative data to recognize the extrahepatic bile duct (EHBD), cystic duct (CD), inferior border of liver S4 (S4), and Rouviere sulcus (RS). The purpose of this research was to evaluate how the AI system affects landmark identification. METHODS: We prepared a 20-s intraoperative video before the serosal incision of Calot's triangle dissection and created a short video with landmarks overwritten by AI. The landmarks were defined as landmark (LM)-EHBD, LM-CD, LM-RS, and LM-S4. Four beginners and four experts were recruited as subjects. After viewing a 20-s intraoperative video, subjects annotated the LM-EHBD and LM-CD. Then, a short video is shown with the AI overwriting landmark instructions; if there is a change in each perspective, the annotation is changed. The subjects answered a three-point scale questionnaire to clarify whether the AI teaching data advanced their confidence in verifying the LM-RS and LM-S4. Four external evaluation committee members investigated the clinical importance. RESULTS: In 43 of 160 (26.9%) images, the subjects transformed their annotations. Annotation changes were primarily observed in the gallbladder line of the LM-EHBD and LM-CD, and 70% of these shifts were considered safer changes. The AI-based teaching data encouraged both beginners and experts to affirm the LM-RS and LM-S4. CONCLUSION: The AI system provided significant awareness to beginners and experts and prompted them to identify anatomical landmarks linked to reducing BDI.

Development of an artificial intelligence system for real-time intraoperative assessment of the Critical View of Safety in laparoscopic cholecystectomy.

BACKGROUND: The Critical View of Safety (CVS) was proposed in 1995 to prevent bile duct injury during laparoscopic cholecystectomy (LC). The achievement of CVS was evaluated subjectively. This study aimed to develop an artificial intelligence (AI) system to evaluate CVS scores in LC. MATERIALS AND METHODS: AI software was developed to evaluate the achievement of CVS using an algorithm for image classification based on a deep convolutional neural network. Short clips of hepatocystic triangle dissection were converted from 72 LC videos, and 23,793 images were labeled for training data. The learning models were examined using metrics commonly used in machine learning. RESULTS: The mean values of precision, recall, F-measure, specificity, and overall accuracy for all the criteria of the best model were 0.971, 0.737, 0.832, 0.966, and 0.834, respectively. It took approximately 6 fps to obtain scores for a single image. CONCLUSIONS: Using the AI system, we successfully evaluated the achievement of the CVS criteria using still images and videos of hepatocystic triangle dissection in LC. This encourages surgeons to be aware of CVS and is expected to improve surgical safety.

An intraoperative artificial intelligence system identifying anatomical landmarks for laparoscopic cholecystectomy: a prospective clinical feasibility trial (J-SUMMIT-C-01).

BACKGROUND: We have implemented Smart Endoscopic Surgery (SES), a surgical system that uses artificial intelligence (AI) to detect the anatomical landmarks that expert surgeons base on to perform certain surgical maneuvers. No report has verified the use of AI-based support systems for surgery in clinical practice, and no evaluation method has been established. To evaluate the detection performance of SES, we have developed and established a new evaluation method by conducting a clinical feasibility trial. METHODS: A single-center prospective clinical feasibility trial was conducted on 10 cases of LC performed at Oita University hospital. Subsequently, an external evaluation committee (EEC) evaluated the AI detection accuracy for each landmark using five-grade rubric evaluation and DICE coefficient. We defined LM-CBD as the expert surgeon's "judge" of the cystic bile duct in endoscopic images. RESULTS: The average detection accuracy on the rubric by the EEC was 4.2 ± 0.8 for the LM-CBD. The DICE coefficient between the AI detection area of the LM-CBD and the EEC members' evaluation was similar to the mean value of the DICE coefficient between the EEC members. The DICE coefficient was high score for the case that was highly evaluated by the EEC on a five-grade scale. CONCLUSION: This is the first feasible clinical trial of an AI system designed for intraoperative use and to evaluate the AI system using an EEC. In the future, this concept of evaluation for the AI system would contribute to the development of new AI navigation systems for surgery.

Development of a cross-artificial intelligence system for identifying intraoperative anatomical landmarks and surgical phases during laparoscopic cholecystectomy.

BACKGROUND: Attention to anatomical landmarks in the appropriate surgical phase is important to prevent bile duct injury (BDI) during laparoscopic cholecystectomy (LC). Therefore, we created a cross-AI system that works with two different AI algorithms simultaneously, landmark detection and phase recognition. We assessed whether landmark detection was activated in the appropriate phase by phase recognition during LC and the potential contribution of the cross-AI system in preventing BDI through a clinical feasibility study (J-SUMMIT-C-02). METHODS: A prototype was designed to display landmarks during the preparation phase and Calot's triangle dissection. A prospective clinical feasibility study using the cross-AI system was performed in 20 LC cases. The primary endpoint of this study was the appropriateness of the detection timing of landmarks, which was assessed by an external evaluation committee (EEC). The secondary endpoint was the correctness of landmark detection and the contribution of cross-AI in preventing BDI, which were assessed based on the annotation and 4-point rubric questionnaire. RESULTS: Cross-AI-detected landmarks in 92% of the phases where the EEC considered landmarks necessary. In the questionnaire, each landmark detected by AI had high accuracy, especially the landmarks of the common bile duct and cystic duct, which were assessed at 3.78 and 3.67, respectively. In addition, the contribution to preventing BDI was relatively high at 3.65. CONCLUSIONS: The cross-AI system provided landmark detection at appropriate situations. The surgeons who previewed the model suggested that the landmark information provided by the cross-AI system may be effective in preventing BDI. Therefore, it is suggested that our system could help prevent BDI in practice. Trial registration University Hospital Medical Information Network Research Center Clinical Trial Registration System (UMIN000045731).

Apoptosis-related factors are relevant to progression of pancreatic neuroendocrine tumors.

BACKGROUND: Multidisciplinary therapy centered on antitumor drugs is indicated in patients with unresectable pancreatic neuroendocrine tumors (PanNET). However, the criteria for selection of optimal therapeutic agents is controversial. The aim of this study was to assess the malignancy of PanNET for optimal therapeutic drug selection. METHODS: Forty-seven patients with PanNET who underwent surgery were reviewed retrospectively, and immunohistochemical characteristics, including expression of GLUT1, SSTR2a, SSTR5, Survivin, X-chromosome-linked inhibitor of apoptosis protein (XIAP), and Caspase3 in the resected specimens, were investigated. Relapse-free survival (RFS) and overall survival (OS) were evaluated with regard to the characteristics using the Kaplan-Meier method and compared with the log-rank test. RESULTS: GLUT1 expression showed significant correlation with sex (p = 0.036) and mitotic rate (p = 0.048). Survivin and XIAP expression showed significant correlation with T-stage (p = 0.014 and 0.009), p-Stage (p = 0.028 and 0.045), and mitotic rate (p = 0.023 and 0.007). XIAP expression also significantly influenced OS (p = 0.044). CONCLUSIONS: Survivin and XIAP correlated with grade of malignancy, and expression of XIAP in particular was associated with a poor prognosis. Expression of these proteins may be a useful indicator to select optimal therapeutic agents in PanNET.