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.

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.

Feasibility of laparoscopic and endoscopic cooperative surgery for gastric gastrointestinal stromal tumor with tumor diameter of >5 cm.

BACKGROUND: Laparoscopic and endoscopic cooperative surgery (LECS) is an effective treatment for gastric gastrointestinal stromal tumors (GISTs). The utility of LECS for gastric GISTs of > 5 cm remains controversial. This study was performed to investigate the feasibility of LECS for gastric GISTs with a tumor diameter of >5 cm. METHODS: We analyzed 43 patients with gastric GISTs who underwent LECS or laparoscopic partial gastrectomy (Lap-Partial Gx). We compared the surgical outcomes of LECS versus Lap-Partial Gx and of LECS for a tumor diameter of > 5 versus ≤ 5 cm. RESULTS: In the comparison of LECS versus Lap-Partial Gx, there were no significant intergroup differences in the operative time or blood loss volume. The morbidity rate was similar between the groups. No postoperative mortality occurred in either group. In the comparison of LECS for a tumor diameter of > 5 versus ≤ 5 cm, there were no significant intergroup differences in operative time, or blood loss volume. The morbidity rate was similar between the > 5-cm and ≤ 5-cm groups (0.0% vs. 4.5%, respectively ; p = 0.56). Additionally, no recurrence or death occurred during follow-up in either group. CONCLUSION: LECS is a feasible option for gastric GISTs with a tumor diameter of > 5 cm. J. Med. Invest. 71 : 148-153, February, 2024.

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.

Number of Healthy Teeth Can Predict the Response of Rectal Cancer to Chemoradiotherapy: A Retrospective Study.

BACKGROUND: It has been reported that the oral and gut microbiomes are associated with the prognosis in patients who undergo surgery, chemotherapy, and radiation for colorectal cancer. This study is the first to identify a correlation between the number of healthy teeth, which is an oral health indicator, and the efficacy of preoperative chemotherapy for rectal cancer. METHODS: This retrospective single-center study included 30 patients who underwent radical surgery after preoperative chemoradiotherapy (CRT) between December 2013 and June 2021. The relationship between number of teeth before CRT and the efficacy of CRT, CRT-related adverse events, postoperative complications, and long-term postoperative outcomes was examined. RESULTS: The number of healthy teeth was significantly greater in patients with downstaging of their disease than in those without downstaging (P = .027) and in patients with a complete response according to the Response Evaluation Criteria in Solid Tumors than in those who did not have a complete response (P = .014). Patients were divided into two groups according to whether they had ≥15 teeth or ≤14 teeth. There was no significant between-group difference in CRT-related adverse events. The incidence of all postoperative complications and grade II postoperative complications tended to be higher in patients with ≥15 teeth (P = .071 and P = .092, respectively), as did the 5-year overall survival rate (P = .083) and the 5-year disease-free rate (P = .007). DISCUSSION: The number of healthy teeth predicted the response to preoperative CRT, postoperative complications, and the outcome of subsequent surgery in patients with rectal cancer.

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.

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.

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.

Conversion surgery after successful response to chemotherapy (S-1 + oxaliplatin + nivolumab) in a patient with stage IV gastric cancer with peritoneal metastasis (P1, CY1): a case report.

We here present a case report of a patient with Stage IV gastric cancer with peritoneal metastasis (P1, CY1) who underwent conversion surgery after a successful response to chemotherapy (S-1 + oxaliplatin + nivolumab). The patient was a woman in her 60 s. Her chief complaint was epigastric pain. Upper gastrointestinal endoscopy showed Type 4 advanced carcinoma on the lesser curvature of the gastric body. Biopsy showed Group 5 (poorly differentiated adenocarcinoma) and HER2 was negative. Staging laparoscopy revealed seeding in the round ligament of the liver (P1) and adenocarcinoma cells in ascites (CY1). Ten courses of chemotherapy (S-1 + oxaliplatin + nivolumab) were administered, after which contrast-enhanced computed tomography showed that the primary tumor had shrunk and seeding was no longer detectable. Upper gastrointestinal endoscopy revealed scar-like changes. A second staging laparoscopy revealed that ascites cytology was negative and a biopsy of the round ligament of the liver showed no malignant cells (P0, CY0). Conversion surgery comprising laparoscopic total gastrectomy with D2 lymph node dissection and resection of the round ligament of the liver was performed. The postoperative course was uneventful. Histopathological examination of the resected specimen revealed no tumor cells in the gastric mesentery or the round ligament of the liver. The pathological diagnosis was gastric cancer [M, U, L, Less, Ant, Post, type4, T3(SS), N0, M0 (H0, P0, CY0), ypStage IIA]. Adjuvant chemotherapy (S-1) was commenced. The patient is still alive 7 months later with no evidence of recurrence.

A case of laparoscopically assisted transperineal repair of anterior enterocele dehiscence with small bowel evisceration after robot-assisted radical cystectomy.

We herein report a case of successful laparoscopically assisted transperineal repair of anterior enterocele dehiscence with small bowel evisceration after robot-assisted radical cystectomy. A 75-year-old woman underwent robot-assisted radical cystectomy with anterior vaginectomy and urethrectomy for bladder cancer (pTisN0M0). Vaginal reconstruction was performed using the posterior vaginal wall. Four months after surgery, she presented with small bowel evisceration due to anterior enterocele dehiscence. She underwent laparoscopically assisted transperineal repair. The anterior enterocele dehiscence did not occur at the vaginal closure site but instead between the vaginal wall and posterior pubic bone. No recurrence had developed at 2 months postoperatively.