Circulating Exosomal MicroRNA Signature Predicts Peritoneal Metastasis in Patients with Advanced Gastric Cancer.

BACKGROUND: Despite a radical operation, about half of gastric cancer (GC) patients with advanced GC experience peritoneal metastasis (PM), and the patients with PM have a poor prognosis. However, because staging laparoscopy was a highly invasive procedure for patients, identification of PM using a liquid biopsy can be useful for patients with GC. METHODS: This study analyzed two genome-wide miRNA expression profiling datasets (GSE164174 and TCGA). The study prioritized biomarkers in pretreatment plasma specimens from clinical training and validation cohorts of patients with GC. The authors developed an integrated exosomal miRNA panel and established a risk-stratification model, which was combined with the miRNA panel and currently used tumor markers (CEA, CA19-9, CA125, and CA72-4 levels). RESULTS: The comprehensive discovery effort identified a four-miRNA panel that robustly predicted the metastasis with excellent accuracy in the TCGA dataset (area under the curve [AUC] 0.86). A circulating exosomal miRNA panel was established successfully with remarkable diagnostic accuracy in the clinical training (AUC 0.85) and validation (AUC 0.86) cohorts. Moreover, the predictive accuracy of the panel was significantly superior to that of conventional clinical factors (P < 0.01), and the risk-stratification model was dramatically superior to the panel and currently used clinical factors for predicting PM (AUC 0.94; univariate: odds ratio [OR] 77.00 [P < 0.01]; multivariate OR 57.71 [P = 0.01]). CONCLUSIONS: The novel risk-stratification model for predicting PM has potential for clinical translation as a liquid biopsy assay for patients with GC. The study findings highlight the potential clinical impact of the model for improved selection and management of patients with GC.

Blue light irradiation inhibits the M2 polarization of the cancer-associated macrophages in colon cancer.

Recent studies have shown that blue light-emitting diode (LED) light has anti-tumor effects, suggesting the possibility of using visible light in cancer therapy. However, the effects of blue light irradiation on cells in the tumor microenvironment, including tumor-associated macrophages (TAMs), are unknown. Here, THP-1 cells were cultured in the conditioned medium (CM) of HCT-116 cells to prepare TAMs. TAMs were divided into LED-irradiated and control groups. Then, the effects of blue LED irradiation on TAM activation were examined. Expression levels of M2 macrophage markers CD163 and CD206 expression were significantly decreased in LED-irradiated TAMs compared with the control group. While control TAM-CM could induce HCT-116 cell migration, these effects were not observed in cells cultured in TAM-CM with LED irradiation. Vascular endothelial growth factor (VEGF) secretion was significantly suppressed in LED-exposed TAMs. PD-L1 expression was upregulated in HCT-116 cells cultured with TAM-CM but attenuated in cells cultured with LED-irradiated TAM-CM. In an in vivo model, protein expression levels of F4/80 and CD163, which are TAM markers, were reduced in the LED-exposed group. These results indicate that blue LED light may have an inhibitory effect on TAMs, as well as anti-tumor effects on colon cancer cells.

Role of stromal PD-L1 expression in colorectal liver metastasis.

BACKGROUND AND AIM: The outcomes of immune checkpoint blockade for colorectal cancer (CRC) treatment are unsatisfactory. Furthermore, the efficacy of immune checkpoint blockade for liver metastasis of various cancer is poor. Here, we investigated the relationship between stromal programmed death-ligand 1 (PD-L1) expression and the prognosis of patients with colorectal cancer liver metastasis (CRLM). METHODS: The present study enrolled 84 CRLM patients who underwent surgery (R0) for CRC. Immunohistochemistry was performed to analyze stromal PD-L1 expression in CRLM. RESULTS: Stromal PD-L1 was expressed in 52.3% of CRLM samples, which was associated with fewer not optimally resectable metastases (p = 0.04). Stromal PD-L1 also tended to associate with a lower tumor grade (p = 0.08). Stromal PD-L1-positive patients had longer overall survival (p = 0.003). Multivariate analysis identified stromal PD-L1 expression (p = 0.008) and poorer differentiation (p < 0.001) as independent prognostic indicators. Furthermore, stromal PD-L1 expression was correlated to a high number of tumor-infiltrating lymphocytes (TILs). Stromal PD-L1- and low TIL groups had shorter OS than stromal PD-L1 + and high TIL groups (46.6% vs. 81.8%, p = 0.05) Stromal PD-L1-positive patients had longer disease-free survival (DFS) (p = 0.03) and time to surgical failure (p = 0.001). Interestingly, stromal PD-L1 expression was positively related to the desmoplastic subtype (p = 0.0002) and inversely related to the replacement subtype of the histological growth pattern (p = 0.008). CONCLUSIONS: Stromal PD-L1 expression may be a significant prognostic marker for CRLM.

Comparison of the short-term surgical outcomes of lateral lymph node dissection for low rectal cancer using a robotic-assisted transabdominal approach alone or supported by a transanal approach.

BACKGROUND: Lateral lymph node metastases are a major cause of local recurrence after surgery for advanced low rectal cancer. Lateral lymph node dissection (LLND) may reduce the risk of local recurrence in patients with suspected lateral lymph node metastasis. Recent reports have shown that robotic-assisted LLND can help to reduce the postoperative complication rate, such as urinary disturbance. Furthermore, with the advent of transanal total mesorectal excision, a novel LLND procedure that combines a transabdominal approach with a transanal approach has been reported. This study aimed to clarify the safety and feasibility of robotic-assisted LLND supported by a transanal approach for advanced low rectal cancer. METHODS: Thirty-nine patients diagnosed to have low rectal cancer between June 2019 and May 2023 were retrospectively enrolled and divided according to whether they underwent LLND via a robotic-assisted transabdominal approach alone (transabdominal group, n = 19) or in combination with a transanal approach (2team group, n = 20). The patient characteristics and short-term surgical outcomes were compared between the two groups. RESULTS: The total operation time was significantly shorter in the 2team group than in the transabdominal group (366 min vs. 513 min, P < 0.001), as was the time taken to perform unilateral LLND (64 min vs. 114 min, P < 0.001). Furthermore, there was significantly less intraoperative bleeding in the 2team group (30 mL vs. 80 mL, P = 0.004). There was no significant between-group difference in postoperative complications. The incidence of postoperative urinary disturbance was satisfactory at 5% in both groups. CONCLUSIONS: The operation time for LLND performed by a robotic-assisted transabdominal approach was shortened when supported by a transanal approach. The frequency of postoperative urinary disturbance was low in both groups. Therefore, robotic-assisted abdominal LLND supported by a transanal approach can be considered a promising treatment option for advanced low rectal cancer.

Prognostic impact of the combination of p16INK4a, p21 and Immunoscore in rectal cancer.

BACKGROUND: The association between p16INK4a and p21, a marker of cellular senescence, and the Immunoscore, an immunological prognostic indicator, in rectal cancer patients undergoing curative surgery were investigated. METHODS: A total of 82 patients who underwent curative surgery for rectal cancer were evaluated. The resected specimens were analyzed for p16INK4a, p21, CD3 and CD8 expression by immunohistochemistry. Immunoscore was calculated on the basis of CD3 and CD8 expressions. The clinicopathological characteristics and long-term outcomes were evaluated. RESULTS: Among the 82 patients, 24 (29.3%) were p16INK4a-positive and 11 (13.4%) were p21-positive. The patients were classified into the following five Immunoscore groups (IS0-5). IS0, IS1 and IS2 were classified as the low Immunoscore group (45 patients, 54.9%) and IS3 and IS4 as the high Immunoscore group (37 patients, 45.1%). There was no significant difference in age, sex, body mass index, American Society of Anesthesiologists physical status, depth of invasion of the tumor, lymph node metastasis and histological classification of the tumor with p16INK4a or p21 expression or Immunoscore. p16INK4a-positive expression and low Immunoscore each showed a tendency to indicate poor prognosis of disease-free survival (DFS). Patients with the combination of p16INK4a and p21 positivity and with p16INK4a positivity and low Immunoscore showed significantly poor prognosis of DFS. Patients with p21 positive positivity and low Immunoscore tended to have worse DFS. CONCLUSIONS: p16INK4a, p21 and Immunoscore may be prognostic indicators of rectal cancer. The combination of them may provide more accurate prognostic prediction than either factor alone.

Preoperative evaluation to determine the difficulty of No. 6 lymphadenectomy in laparoscopic gastrectomy.

BACKGROUND: Laparoscopic gastrectomy (LG) requires a long learning curve because of the complicated surgical procedures. Infrapyloric (No. 6) lymph node dissection (LND) is one of the difficult procedures in LG, especially for trainees. This study investigated the impact of the prediction of the difficulty of No. 6 LND. METHODS: We retrospectively reviewed the preoperative computed tomography (CT) images and individual operative video records of 57 patients who underwent LG with No. 6 LND to define and predict the No. 6 LND difficulty. To evaluate whether prediction of the difficulty of No. 6 LND could improve surgical outcomes, 48 patients who underwent laparoscopic distal gastrectomy were assessed (30 patients without prediction by a qualified surgeon and 18 patients with prediction by a trainee). RESULTS: The anatomical characteristic that LND required > 2 cm of dissection along the right gastroepiploic vein was defined as difficulty of No. 6 LND. Of the 57 LG patients, difficulty was identified intraoperatively in 21 patients (36.8%). Among the several evaluated anatomical parameters, the length between the right gastroepiploic vein and the right gastroepiploic artery in the maximum intensity projection in contrast-enhanced CT images was significantly correlated with the intraoperative difficulty of No. 6 LND (p < 0.0001). Surgical outcomes, namely intraoperative minor bleeding, postoperative pancreatic fistula, and drain amylase concentration were not significantly different between LG performed by a trainee with prediction compared with that by a specialist without prediction. CONCLUSIONS: Preoperative evaluation of the difficulty of No. 6 LND is useful for trainees, to improve surgical outcomes.

An exosome-based liquid biopsy signature for pre-operative identification of lymph node metastasis in patients with pathological high-risk T1 colorectal cancer.

BACKGROUND: According to current guidelines, more than 70% of patients with invasive submucosal colorectal cancer (T1 CRC) undergo a radical operation with lymph node dissection, even though only ~ 10% have lymph node metastasis (LNM). Hence, there is imperative to develop biomarkers that can help robustly identify LNM-positive patients to prevent such overtreatments. Given the emerging interest in exosomal cargo as a source for biomarker development in cancer, we examined the potential of exosomal miRNAs as LNM prediction biomarkers in T1 CRC. METHODS: We analyzed 200 patients with high-risk T1 CRC from two independent cohorts, including a training (n = 58) and a validation cohort (n = 142). Cell-free and exosomal RNAs from pre-operative serum were extracted, followed by quantitative reverse-transcription polymerase chain reactions for a panel of miRNAs. RESULTS: A panel of four miRNAs (miR-181b, miR-193b, miR-195, and miR-411) exhibited robust ability for detecting LNM in the exosomal vs. cell-free component. We subsequently established a cell-free and exosomal combination signature, successfully validated in two independent clinical cohorts (AUC, 0.84; 95% CI 0.70-0.98). Finally, we developed a risk-stratification model by including key pathological features, which reduced the false positive rates for LNM by 76% without missing any true LNM-positive patients. CONCLUSIONS: Our novel exosomal miRNA-based liquid biopsy signature robustly identifies T1 CRC patients at risk of LNM in a preoperative setting. This could be clinically transformative in reducing the significant overtreatment burden of this malignancy.

A Liquid Biopsy Signature for the Detection of Patients With Early-Onset Colorectal Cancer.

BACKGROUND & AIMS: Early-onset colorectal cancer (EOCRC) is a distinct clinical and molecular entity with poor survival outcomes compared with late-onset CRC. Although the incidence of EOCRC is rising, current CRC screening strategies have several limitations in diagnostic performance for EOCRC. In view of this clinical challenge, novel and robust biomarkers for detection of EOCRC are necessary. The aim of this study was to develop a circulating micro RNA (miRNA) signature for the diagnosis of patients with EOCRC. METHODS: A systematic discovery approach by analyzing a large, publicly available, noncoding RNA expression profiling dataset (GSE115513) was used. A panel of miRNAs was identified, which was subsequently validated in blood samples from patients with EOCRC in 2 independent cohorts (n = 149) compared with controls (n = 110) and pre/postoperative plasma specimens (n = 22) using quantitative reverse-transcription polymerase chain reaction assays. RESULTS: In the discovery phase, 4 miRNAs were found to be expressed in blood samples. A combination signature of these 4 miRNAs (miR-193a-5p, miR-210, miR-513a-5p, and miR-628-3p) yielded an area under the curve of 0.92 (95% confidence interval, 0.85-0.96) for identification of EOCRC in the training cohort. The miRNA panel performance was then confirmed in an independent validation cohort (area under the curve, 0.88; 95% confidence interval, 0.82-0.93). Moreover, the miRNA panel robustly identified patients with early-stage EOCRC (P < .001). The decreased expression of miRNAs in postsurgery plasma specimens indicated their tumor specificity. CONCLUSIONS: Our novel miRNA signature for the diagnosis of EOCRC has the potential to identify patients with EOCRC with high accuracy for clinical application in the noninvasive diagnosis of EOCRC.

Visualization of the pelvic nerves using magnetic resonance imaging for rectal cancer surgery.

BACKGROUND: This study evaluated the visualization of the pelvic nerves using magnetic resonance imaging (MRI) combined with computed tomography (CT) to synthesize three-dimensional (3D) reconstruction images of the pelvic organs. METHODS: The CT and MRI scans were performed for patients with rectal cancer who underwent surgery. The out-of-phase image of LAVA-Flex was used to identify the pelvic nerves. The images of the pelvic nerves were extracted from the MRI scans, and those of the arteries and rectum and pelvis were extracted from the CT scans. Each extracted organ image was used to synthesize 3D reconstruction images. RESULTS: The MRI scan allowed adequate visualization of the pelvic splanchnic nerves, inferior hypogastric plexus, and obturator nerves. The comparison of 3D reconstruction images and intraoperative findings showed matched images. CONCLUSION: We visualized the pelvic nerves using MRI and synthesized 3D reconstruction images of the pelvic organs. Preoperative confirmation of the location of the pelvic organs is important to prevent unanticipated injury during rectal cancer surgery.

Transanal lateral lymph node dissection with intraoperative hologram support in low rectal cancer.

BACKGROUND: In Japan, the standard treatment for stage II/III advanced low rectal cancer is total mesorectal excision plus lateral lymph node dissection (LLND). There are also recent reports on the use of transanal LLND. However, the transanal anatomy is difficult to understand, and additional support tools are required to improve the surgical safety. The present study examined the utility of holograms with mixed reality as an intraoperative support tool for assessing the complex pelvic anatomy. METHODS: Polygon (stereolithography) files of patients' pelvic organs were created and exported from the SYNAPSE VINCENT imaging system and uploaded into the Holoeyes MD virtual reality software. Three-dimensional images were automatically converted into patient-specific holograms. Each hologram was then installed into a head mount display (HoloLens2), and the surgeons and assistants wore the HoloLens2 when they performed transanal LLND. Twelve digestive surgeons with prior practice in hologram manipulation evaluated the utility of the intraoperative hologram support by means of a questionnaire. RESULTS: Intraoperative hologram support improved the surgical understanding of the lateral lymph node region anatomy. In the questionnaire, 75% of the surgeons answered that the hologram accurately reflected the anatomy, and 92% of the surgeons answered that the anatomy was better understood by simulating the hologram intraoperatively than preoperatively. Moreover, 92% of the surgeons agreed that intraoperative holograms were a useful support tool for improving the surgical safety. CONCLUSIONS: Intraoperative hologram support improved the surgical understanding of the pelvic anatomy for transanal LLND. Intraoperative holograms may represent a next-generation surgical tool for transanal LLND.

The application of enhanced recovery after surgery in total gastrectomy: a propensity score-matched analysis.

BACKGROUND: This study aimed to investigate the feasibility and safety of our enhanced recovery after surgery protocol including early oral intake and omitting nasogastric tube (NGT) placement after total gastrectomy. METHODS: We analyzed 182 consecutive patients who underwent total gastrectomy. The clinical pathway was changed in 2015, and patients were divided into 2 groups (conventional group and modified group). Postoperative complications, bowel movement, and postoperative hospital stays were compared in the two groups in all cases and propensity score matching (PSM). RESULTS: Flatus and defecation were significantly earlier in the modified group compared with those in the conventional group (flatus: 2 (1-5) days vs 3 (2-12) days, p = 0.03; defecation: 4 (1-14) days vs 6 (2-12) days p = 0.04). The postoperative hospital stay was 18 (6-90) days in the conventional group and 14 (7-74) days in the modified group (p = 0.009). Days until discharge criteria were met were earlier in the modified group compared with that in the conventional group (10 (7-69) days vs 14 (6-84) days p = 0.01). Overall and severe complications occurred in nine patients (12.6%) and three patients (4.2%) in the conventional group and twelve patients (10.8%) and four patients (3.6%) in the modified group, respectively (p = 0.70 and p = 0.83) in all cases. In PSM, there is no significant difference between the two groups concerning the postoperative complications (overall complication 6 (12.5%) vs 8 (16.7%) p = 0.56, severe complications 1 (2%) vs 2 (4.2%) p = 0.83). CONCLUSIONS: Modified ERAS for total gastrectomy may be feasible and safe.

Stapler insertion angle toward the esophagus reduces the incidence of early postoperative Roux stasis syndrome after distal gastrectomy in minimally invasive surgery.

BACKGROUND: Roux stasis syndrome (RSS) after Roux-en-Y (RY) reconstruction significantly prolongs the hospital stay and decreases the quality of life. The purpose of the present study was to evaluate the incidence of RSS in patients who underwent distal gastrectomy for gastric cancer and to identify the factors related to the development of RSS after mechanical RY reconstruction in minimally invasive surgery (MIS). METHODS: This study included 134 patients who underwent distal gastrectomy in MIS with mechanical RY anastomosis. RSS was defined as the presence of symptoms such as nausea, vomiting, or abdominal fullness, and the confirmation of delayed gastric emptying on imaging or gastrointestinal fiber testing. Clinical data were checked, including body mass index, operative procedure, age, sex, operative time, blood loss volume, extent of lymph node dissection, final stage, stapler insertion angle, method of entry hole closure. The relationship between the incidence of RSS and these factors was analyzed. RESULTS: RSS occurred in 24 of 134 patients (17.9%). RSS occurred significantly more frequently in patients with D2 lymphadenectomy than in patients with D1 + lymphadenectomy (p = 0.04). All patients underwent side-to-side anastomosis via the antecolic route. The incidence of RSS was significantly greater in patients with a stapler insertion angle toward the greater curvature (n = 20, 22.5%) versus the esophagus (n = 4, 8.9%) (p = 0.04). The multivariate logistic regression model revealed that the stapler insertion angle to the greater curvature is identified as independent risk factor for RSS (OR 3.23, 95%Cl 1.01-10.3, p = 0.04). CONCLUSION: Stapler insertion angle toward the esophagus may reduce the incidence of early postoperative RSS rather than toward the greater curvature.

Utility of robotic surgery for Siewert type II/III adenocarcinoma of esophagogastric junction: transhiatal robotic versus laparoscopic approach.

BACKGROUND: Robotic surgery (RS) has been rapidly adopted for gastric cancer and adenocarcinoma of the esophagogastric junction (AEG). However, the utility of RS for Siewert type II/III AEG remains unclear. METHODS: Forty-one patients who underwent either transhiatal RS (n = 15) or laparoscopic surgery (LS) (n = 26) for Siewert type II/III AEG were enrolled in this study. The surgical outcomes of the two groups were compared. RESULTS: In the entire cohort, there were no significant intergroup differences in the operative time, blood loss volume, or number of retrieved lymph nodes. The length of the postoperative hospital stay was shorter in the RS group than in the LS group (14.20 ± 7.10 days vs. 18.73 ± 17.82 days, respectively; p = 0.0388). The morbidity rate (Clavien-Dindo grade ≥ 2) was similar between the groups. In the Siewert II cohort, there were no significant intergroup differences in short-term outcomes. In the entire cohort, there was no significant difference between the RS and LS groups in the 3-year overall survival rate (91.67% vs. 91.48%, N.S.) or 3-year disease-free survival rate (91.67% vs. 91.78%, N.S.), respectively. Likewise, in the Siewert type II cohort, there was no significant difference between the RS and LS groups in the 3-year overall survival rate (80.00% vs. 93.33%, N.S.) or 3-year disease-free survival rate (80.00% vs. 94.12%, N.S.), respectively. CONCLUSIONS: Transhiatal RS for Siewert II/III AEG was safe and contributed to similar short-term and long-term outcomes compared with LS.

A blood-based noninvasive miRNA signature for predicting survival outcomes in patients with intrahepatic cholangiocarcinoma.

BACKGROUND: The prognosis in patients with intrahepatic cholangiocarcinoma (ICC) is generally poor. To improve treatment selection, we sought to identify microRNA (miRNA) signature associated with survival outcomes in ICC. METHODS: We first analysed the miRNA expression profiles of primary ICC from two public datasets to identify a miRNA panel to detect patients for short-term survival. We then analysed 309 specimens, including 241 FFPE samples from two clinical cohorts (training: n = 177; validation: n = 64) and matched plasma samples (n = 68), and developed a risk-stratification model incorporating the panel and CA 19-9 levels to predict survival outcomes in ICC. RESULTS: We identified a 7-miRNA panel that robustly classified patients with poor outcomes in the discovery cohorts (AUC = 0.80 and 0.88, respectively). We subsequently trained this miRNA panel in a clinical cohort (AUC = 0.83) and evaluated its performance in an independent validation cohort (AUC = 0.82) and plasma samples from the additional validation cohort (AUC = 0.78). Patients in both clinical cohorts who were classified as high-risk had significantly worse prognosis (p < 0.01). The risk-stratification model demonstrated superior performance compared to models (AUC = 0.85). CONCLUSIONS: We established a novel miRNA signature that could robustly predict survival outcomes in resected tissues and liquid biopsies to improve the clinical management of patients with ICC.

A Liquid Biopsy Assay for Noninvasive Identification of Lymph Node Metastases in T1 Colorectal Cancer.

BACKGROUND & AIMS: We recently reported use of tissue-based transcriptomic biomarkers (microRNA [miRNA] or messenger RNA [mRNA]) for identification of lymph node metastasis (LNM) in patients with invasive submucosal colorectal cancers (T1 CRC). In this study, we translated our tissue-based biomarkers into a blood-based liquid biopsy assay for noninvasive detection of LNM in patients with high-risk T1 CRC. METHODS: We analyzed 330 specimens from patients with high-risk T1 CRC, which included 188 serum samples from 2 clinical cohorts-a training cohort (N = 46) and a validation cohort (N = 142)-and matched formalin-fixed paraffin-embedded samples (N = 142). We performed quantitative reverse-transcription polymerase chain reaction, followed by logistic regression analysis, to develop an integrated transcriptomic panel and establish a risk-stratification model combined with clinical risk factors. RESULTS: We used comprehensive expression profiling of a training cohort of LNM-positive and LMN-negative serum specimens to identify an optimized transcriptomic panel of 4 miRNAs (miR-181b, miR-193b, miR-195, and miR-411) and 5 mRNAs (AMT, forkhead box A1 [FOXA1], polymeric immunoglobulin receptor [PIGR], matrix metalloproteinase 1 [MMP1], and matrix metalloproteinase 9 [MMP9]), which robustly identified patients with LNM (area under the curve [AUC], 0.86; 95% confidence interval [CI], 0.72-0.94). We validated panel performance in an independent validation cohort (AUC, 0.82; 95% CI, 0.74-0.88). Our risk-stratification model was more accurate than the panel and an independent predictor for identification of LNM (AUC, 0.90; univariate: odds ratio [OR], 37.17; 95% CI, 4.48-308.35; P < .001; multivariate: OR, 17.28; 95% CI, 1.82-164.07; P = .013). The model limited potential overtreatment to only 18% of all patients, which is dramatically superior to pathologic features that are currently used (92%). CONCLUSIONS: A novel risk-stratification model for noninvasive identification of T1 CRC has the potential to avoid unnecessary operations for patients classified as high-risk by conventional risk-classification criteria.

A Transcriptomic Signature for Risk-Stratification and Recurrence Prediction in Intrahepatic Cholangiocarcinoma.

BACKGROUND AND AIMS: Tumor recurrence is frequent even in intrahepatic cholangiocarcinoma (ICC), and improved strategies are needed to identify patients at highest risk for such recurrence. We performed genome-wide expression profile analyses to discover and validate a gene signature associated with recurrence in patients with ICC. APPROACH AND RESULTS: For biomarker discovery, we analyzed genome-wide transcriptomic profiling in ICC tumors from two public data sets: The Cancer Genome Atlas (n = 27) and GSE107943 (n = 28). We identified an eight-gene panel (BIRC5 [baculoviral IAP repeat containing 5], CDC20 [cell division cycle 20], CDH2 [cadherin 2], CENPW [centromere protein W], JPH1 [junctophilin 1], MAD2L1 [mitotic arrest deficient 2 like 1], NEIL3 [Nei like DNA glycosylase 3], and POC1A [POC1 centriolar protein A]) that robustly identified patients with recurrence in the discovery (AUC = 0.92) and in silico validation cohorts (AUC = 0.91). We next analyzed 241 specimens from patients with ICC (training cohort, n = 64; validation cohort, n = 177), followed by Cox proportional hazard regression analysis, to develop an integrated transcriptomic panel and establish a risk-stratification model for recurrence in ICC. We subsequently trained this transcriptomic panel in a clinical cohort (AUC = 0.89; 95% confidence interval [CI] = 0.79-0.95), followed by evaluating its performance in an independent validation cohort (AUC = 0.86; 95% CI = 0.80-0.90). By combining our transcriptomic panel with various clinicopathologic features, we established a risk-stratification model that was significantly superior for the identification of recurrence (AUC = 0.89; univariate HR = 6.08, 95% CI = 3.55-10.41, P < 0.01; and multivariate HR = 3.49, 95% CI = 1.81-6.71, P < 0.01). The risk-stratification model identified potential recurrence in 85% of high-risk patients and nonrecurrence in 76% of low-risk patients, which is dramatically superior to currently used pathological features. CONCLUSIONS: We report a transcriptomic signature for risk-stratification and recurrence prediction that is superior to currently used clinicopathological features in patients with ICC.

Propensity Score-Matched Analysis of the Short- and Long-Term Outcomes of Robotic Versus Laparoscopic Gastrectomy for Gastric Cancer.

BACKGROUND: Robotic gastrectomy (RG) has been rapidly adopted for gastric cancer (GC) treatment. However, the benefits of RG over laparoscopic gastrectomy (LG) for GC remain unclear. METHODS: A total of 451 patients who underwent either RG (n = 83) or LG (n = 368) for GC were enrolled in this study. A 1:1 matched, propensity score-matched analysis was performed using the following factors: age, sex, body mass index, pT, pN, pStage, tumor location, vessel invasion, tumor markers, surgical procedure, reconstruction method, extent of lymphadenectomy, and Endoscopic Surgical Skill Qualification System qualified surgeon as an operator. The surgical outcomes of the two groups were compared. RESULTS: A well-balanced cohort of 158 patients was analyzed (n = 79 in the RG group, n = 79 in the LG group). Regarding the short-term outcomes, the respective blood loss volume, drain amylase content, and number of retrieved lymph nodes in the RG and LG groups were 38.62 ± 73.06 ml and 67.53 ± 108.20 ml (p < 0.05), 450 ± 371 IU/l and 1590 ± 6392 IU/l (p < 0.01), and 35.02 ± 15.51 and 25.28 ± 11.70 (p < 0.01). The morbidity rate was similar between the RG and LG groups (not significant [NS]). Regarding the long-term survival outcomes, there were no intergroup differences in 3-year overall survival (91.72% in the RG group vs. 83.39% in the LG group: NS) and 3-year, disease-free survival (93.31% in the vs. 90.44%: NS). CONCLUSIONS: RG was safe and contributed to better short-term outcomes and similar long-term survival outcomes compared with LG.

Role of IDO expression in patients with locally advanced rectal cancer treated with preoperative chemoradiotherapy.

BACKGROUND: The role of the immune system in locally advanced rectal cancer (LARC) following preoperative chemoradiotherapy (CRT) has been widely investigated in recent years. This study examined the prognostic significance of indoleamine-pyrrole 2,3-dioxygenase (IDO) expression in patients with LARC who received preoperative CRT. METHODS: Ninety patients with LARC who underwent preoperative CRT and curative resection were enrolled. IDO and programmed death-ligand 1 (PD-L1) expression was evaluated by immunohistochemistry. RESULTS: Clinicopathological factors did not significantly differ between patients with positive or negative IDO expression, excluding the correlation of positive IDO expression with better tumor differentiation (p = 0.02). IDO expression was not associated with pathological response (p = 0.44), but it was associated with PD-L1 expression. The 5-year overall survival (OS) rate was significantly worse in the IDO-positive group than in the IDO-negative group (64.8% vs. 85.4%, p = 0.02). Univariate analysis identified IDO and PD-L1 expression (p = 0.02), surgical procedure (p = 0.01), final pathological stage (p = 0.003), lymph node metastasis (p < 0.001), and lymphatic invasion (p = 0.002) as significant prognostic factors for OS. Multivariate analysis revealed that IDO expression (HR: 7.10, p = 0.0006), surgical procedure (HR: 5.03, p = 0.01), lymph node metastasis (HR: 2.37, p = 0.04) and lymphatic invasion (HR: 4.97, p = 0.01) were independent prognostic indicators. Disease-free survival was not correlated with IDO or PD-L1 expression. CONCLUSIONS: IDO expression in patients with LARC who received preoperative CRT could be a potential prognostic indicator. IDO expression could be a useful marker for specifying individual treatment strategies in LARC.

Intraoperative holographic image-guided surgery in a transanal approach for rectal cancer.

PURPOSE: Urethral injury is one of the most important complications in transanal total mesorectal excision (TaTME) in male patients with rectal cancer. The purpose of this study was to investigate holographic image-guided surgery in TaTME. METHODS: Polygon (stereolithography) files were created and exported from SYNAPSE VINCENT, and then uploaded into the Holoeyes MD system (Holoeyes Inc., Tokyo, Japan). After uploading the data, the three-dimensional image was automatically converted into a case-specific hologram. The hologram was then installed into the head mount display, HoloLens (Microsoft Corporation, Redmond, WA). The surgeons and assistants wore the HoloLens when they performed TaTME. RESULTS: In a Wi-Fi-enabled operating room, each surgeon, wearing a HoloLens, shared the same hologram and succeeded in adjusting the hologram by making simple hand gestures from their respective angles. The hologram contributed to better comprehension of the positional relationships between the urethra and the surrounding pelvic organs during surgery. All surgeons were able to properly determine the dissection line. CONCLUSIONS: This first experience suggests that intraoperative holograms contributed to reducing the risk of urethral injury and understanding transanal anatomy. Intraoperative holograms have the potential to become a new next-generation surgical support tool for use in spatial awareness and the sharing of information between surgeons.

The correlation of immunoscore and frailty in colorectal cancer.

BACKGROUND: The Immunoscore is a useful prognostic and predictive factor for colorectal cancer. Frailty predicts overall and recurrence-free survival following resection of colorectal cancer, and the immunosuppressive state of frailty might affect tumor progression. This study investigated the relationship between the Immunoscore and frailty in colorectal cancer. METHODS: This retrospective study included patients who underwent radical surgery for stage II and III colorectal cancer (n = 108). Patients were divided into frail (n = 11) and non-frail (n = 97) groups, and low (IS0-2) (n = 70) and high (IS3-4) Immunoscore groups (n = 38), for comparison. RESULTS: American Society of Anesthesiologists physical status was higher, tumor diameter was larger, number of well-differentiated tumors was higher, albumin was lower, 5-year overall survival (OS) was lower (frail group: 50.0%, non-frail group: 90.5%, p < 0.001) and 5-year disease-free survival (DFS) was lower (frail group: 36.4%, non-frail group: 75.2%, p = 0.024) in the frail than in the non-frail group. Left colon cancer was more, 5-year OS was lower (IS0-2 group: 82.0%, IS3-4 group: 96.7%, p = 0.040) and 5-year DFS was lower (IS0-2 group: 66.3%, IS3-4 group: 83.3%, p = 0.043) in the IS0-2 than in the IS3-4 group. The Immunoscore was lower in the frail than in the non-frail group. CONCLUSION: Immunoscore and frailty are prognostic and predictive factors in colorectal cancer, and they are correlated with each other. The immunosuppressive state from frailty might affect this correlation.