Optimal extent of lymph node dissection for high-risk gastric cancer stratified by a national clinical database risk calculator.

BACKGROUND: For patients with gastric cancer, a well-balanced treatment that considers both oncological aspects and surgical risk is demanded. This study aimed to explore the optimal extent of lymph node dissection (LND) for patients with gastric cancer according to surgical risk, stratified by the risk calculator system produced by the Japan National Clinical Database (NCD). PATIENTS AND METHODS: We retrospectively evaluated 187 patients who underwent radical gastrectomy for gastric cancer. Using the median predicted anastomotic leak rate obtained by the NCD risk calculator as the cutoff value, we classified 97 and 90 patients as having high and low risks, respectively. RESULTS: In low-risk patients, although limited LND reduced the postoperative intraabdominal infectious complications (IAIC), multivariate analysis revealed standard LND as an independent prognostic factor that improved Relapse-free survival (RFS). In high-risk patients, the rates of postoperative IAIC and RFS were similar between standard and limited LND. Pancreatic fistula was not observed in the limited dissection group. CONCLUSION: Limited LND might be the optimal treatment strategy for patients with gastric cancer with high surgical risk.

Final analyses of the prospective controlled trial on the efficacy of uracil and tegafur/leucovorin as an adjuvant treatment for stage II colon cancer with risk factors for recurrence using propensity score-based methods (JFMC46-1201).

BACKGROUND: The efficacy of adjuvant chemotherapy for high-risk stage II colon cancer (CC) has not been well established. Using propensity score matching, we previously reported that the 3-year disease-free survival (DFS) rate was significantly higher in patients treated with uracil and tegafur plus leucovorin (UFT/LV) against surgery alone. We report the final results, including updated 5-year overall survival (OS) rates and risk factor analysis outcomes. METHODS: In total, 1902 high-risk stage II CC patients with T4, perforation/penetration, poorly differentiated adenocarcinoma/mucinous carcinoma, and/or < 12 dissected lymph nodes were enrolled in this prospective, non-randomized controlled study based on their self-selected treatment. Oral UFT/LV therapy was administered for six months after surgery. RESULTS: Of the 1880 eligible patients, 402 in Group A (surgery alone) and 804 in Group B (UFT/LV) were propensity score-matched. The 5-year DFS rate was significantly higher in Group B than in Group A (P = 0.0008). The 5-year OS rates were not significantly different between groups. The inverse probability of treatment weighting revealed significantly higher 5-year DFS (P = 0.0006) and 5-year OS (P = 0.0122) rates in group B than in group A. Multivariate analyses revealed that male sex, age ≥ 70 years, T4, < 12 dissected lymph nodes, and no adjuvant chemotherapy were significant risk factors for DFS and/or OS. CONCLUSION: The follow-up data from our prospective non-randomized controlled study revealed a considerable survival advantage in DFS offered by adjuvant chemotherapy with UFT/LV administered for six months over surgery alone in individuals with high-risk stage II CC. TRIAL REGISTRATION: Japan Registry of Clinical Trials: jRCTs031180155 (date of registration: 25/02/2019), UMIN Clinical Trials Registry: UMIN000007783 (date of registration: 18/04/2012).

Involvement of CX3CR1+ cells appearing in the abdominal cavity in the immunosuppressive environment immediately after gastric cancer surgery.

BACKGROUND: Gastric cancer is primarily treated by surgery; however, little is known about the changes in the intraperitoneal immune environment and the prognostic impact of surgery. Surgical stress and cancer-associated inflammation cause immune cells to mobilize into the abdominal cavity via numerous cytokines. One such cytokine, CX3CR1, has various immune-related functions that remain to be fully explained. We characterized the intraperitoneal immune environment by investigating CX3CR1+ cells in intraperitoneal lavage fluid during gastric cancer surgery. METHODS: Lavage fluid samples were obtained from a total of 41 patients who underwent gastrectomy. The relative expression of various genes was analyzed using quantitative real-time PCR. The association of each gene expression with clinicopathological features and surgical outcomes was examined. The fraction of CX3CR1+ cells was analyzed by flow cytometry. Cytokine profiles in lavage fluid samples were investigated using a cytometric beads array. RESULTS: CX3CR1high patients exhibited higher levels of perioperative inflammation in blood tests and more recurrences than CX3CR1low patients. CX3CR1high patients tended to exhibit higher pathological T and N stage than CX3CR1low patients. CX3CR1 was primarily expressed on myeloid-derived suppressor cells and tumor-associated macrophages. In particular, polymorphonuclear myeloid-derived suppressor cells were associated with perioperative inflammation, pathological N, and recurrences. These immunosuppressive cells were associated with a trend toward unfavorable prognosis. Moreover, CX3CR1 expression was correlated with programmed death-1 expression. CONCLUSIONS: Our results suggest that CX3CR1+ cells are associated with an acute inflammatory response, tumor-promotion, and recurrence. CX3CR1 expression could be taken advantage of as a beneficial therapeutic target for improving immunosuppressive state in the future. In addition, analysis of intra-abdominal CX3CR1+ cells could be useful for characterizing the immune environment after gastric cancer surgery.

Effects of an artificial pancreas on postoperative inflammation in patients with esophageal cancer.

PURPOSES: Subtotal esophagectomy for esophageal cancer (EC) is associated with high morbidity rates. Tight glycemic control using an artificial pancreas (AP) is one of the promising strategies to reduce postoperative inflammation and morbidities. However, the effects of tight glycemic control using AP in patients with EC are yet to be fully elucidated. METHOD: This study reviewed 96 patients with EC who underwent subtotal esophagectomy. The postoperative inflammation parameters and morbidity rates were compared between patients who used the AP (n = 27) or not (control group, n = 69). AP is a closed-loop system that comprises a continuous glucose monitor and an insulin pump. RESULTS: The numbers of white blood cells (WBC) and Neutrophils (Neut) were noted to be lower in the AP group than in the control group, but with no significant difference. The ratio in which the number of WBC, Neut, and CRP on each postoperative day (POD) was divided by those tested preoperatively was used to standardize the results. The ratio of WBC and Neut on 1POD was significantly lower in the AP group than in the control group. The rate of surgical site infection was lower in the AP group than in the control group. CONCLUSION: AP significantly decreased WBC and Neut on 1POD; this suggests the beneficial effects of AP in alleviating postoperative inflammation.

The heterogeneity of cancer-associated fibroblast subpopulations: Their origins, biomarkers, and roles in the tumor microenvironment.

The prognosis for patients with cancers known for a highly activated stromal reaction, including diffuse-type (scirrhous) gastric cancer, consensus molecular subtype 4 (CMS4) colorectal cancer, and pancreatic ductal adenocarcinoma, is extremely poor. To explore the resistance of conventional therapy for those refractory cancers, detailed classification and investigation of the different subsets of cancer-associated fibroblasts (CAFs) involved are needed. Recent studies with a single-cell transcriptomics strategy (single-cell RNA-seq) have demonstrated that CAF subpopulations contain different origins and marker proteins with the capacity to either promote or suppress cancer progression. Through multiple signaling pathways, CAFs can promote tumor growth, metastasis, and angiogenesis with extracellular matrix (ECM) remodeling; they can also interact with tumor-infiltrating immune cells and modulate the antitumor immunological state in the tumor microenvironment (TME). Here, we review the recent literature on the various subpopulations of CAFs to improve our understanding of the cell-cell interactions in the TME and highlight future avenues for CAF-targeted therapy.

Prognostic relevance of tumor-resident memory T cells in metastatic lymph nodes of esophageal squamous cell carcinoma.

Tumor-resident memory T (TRM ) cells in primary tumors are reportedly associated with a favorable prognosis in several malignancies. However, the behaviors and functions of TRM cells in regional lymph nodes (LNs) of esophageal cancer remain poorly understood. The aim of this study was to elucidate the effects of TRM cells in regional LNs of esophageal cancer on clinicopathological findings and prognosis. Specimens of esophageal cancer and primary metastatic LNs (recurrent nerve LNs) were obtained from 84 patients who underwent radical esophagectomy between 2011 and 2017. We performed immunohistochemistry to enumerate and analyze TRM cells, and used flow cytometry to investigate the function of TRM cells. TRM cells were observed in both metastatic LNs and primary tumors. TRM cell-rich specimens exhibited reduced lymphatic invasion and LN metastasis and prolonged survival compared with TRM cell-poor specimens. TRM cells in metastatic LNs were more significantly associated with enhanced survival than TRM cells in primary tumors. TRM cells expressed high levels of granzyme B as a cytotoxicity marker. Our results suggested that high TRM cell infiltration in metastatic LNs improves survival even though LN metastasis is commonly associated with poor prognosis. TRM cells possibly contribute to antitumor immunity in regional LNs.

Crohn's Disease-Associated Anorectal Cancer Has a Poor Prognosis With High Local Recurrence: A Subanalysis of the Nationwide Japanese Study.

INTRODUCTION: Colorectal cancer (CRC) is one of the major life-threatening complications in patients with Crohn's disease (CD). Previous studies of CD-associated CRC (CD-CRC) have involved only small numbers of patients, and no large series have been reported from Asia. The aim of this study was to clarify the prognosis and clinicopathological features of CD-CRC compared with sporadic CRC. METHODS: A large nationwide database was used to identify patients with CD-CRC (n = 233) and sporadic CRC (n = 129,783) over a 40-year period, from 1980 to 2020. Five-year overall survival (OS), recurrence-free survival (RFS), and clinicopathological characteristics were investigated. The prognosis of CD-CRC was further evaluated in groups divided by colon cancer and anorectal cancer (RC). Multivariable Cox regression analysis was used to adjust for confounding by unbalanced covariables. RESULTS: Compared with sporadic cases, patients with CD-CRC were younger; more often had RC, multiple lesions, and mucinous adenocarcinoma; and had lower R0 resection rates. Five-year OS was worse for CD-CRC than for sporadic CRC (53.99% vs 71.17%, P < 0.001). Multivariable Cox regression analysis revealed that CD was associated with significantly poorer survival (hazard ratio 2.36, 95% confidence interval: 1.54-3.62, P < 0.0001). Evaluation by tumor location showed significantly worse 5-year OS and RFS of CD-RC compared with sporadic RC. Recurrence was identified in 39.57% of CD-RC cases and was mostly local. DISCUSSION: Poor prognosis of CD-CRC is attributable primarily to RC and high local recurrence. Local control is indispensable to improving prognosis.

Effect of Biologics on the Risk of Advanced-Stage Inflammatory Bowel Disease-Associated Intestinal Cancer: A Nationwide Study.

INTRODUCTION: The aim of this study was to evaluate the effect of biologics on the risk of advanced-stage inflammatory bowel disease (IBD)-associated intestinal cancer from a nationwide multicenter data set. METHODS: The medical records of patients with Crohn's disease (CD) and ulcerative colitis (UC) diagnosed with IBD-associated intestinal neoplasia (dysplasia or cancer) from 1983 to 2020 were included in this study. Therapeutic agents were classified into 3 types: biologics, 5-aminosalicylic acid, and immunomodulators. The pathological cancer stage was compared based on the drug used in both patients with CD and UC. RESULTS: In total, 1,042 patients (214 CD and 828 UC patients) were included. None of the drugs were significantly associated with cancer stage in the patients with CD. In the patients with UC, an advanced cancer stage was significantly associated with less use of biologics (early stage: 7.7% vs advanced stage: 2.0%, P < 0.001), 5-aminosalicylic acid, and immunomodulators. Biologic use was associated with a lower incidence of advanced-stage cancer in patients diagnosed by regular surveillance (biologics [-] 24.5% vs [+] 9.1%, P = 0.043), but this was not the case for the other drugs. Multivariate analysis showed that biologic use was significantly associated with a lower risk of advanced-stage disease (odds ratio = 0.111 [95% confidence interval, 0.034-0.356], P < 0.001). DISCUSSION: Biologic use was associated with a lower risk of advanced IBD-associated cancer in patients with UC but not with CD. The mechanism of cancer progression between UC and CD may be different and needs to be further investigated.

Significance of CD103+ tissue-resident memory T cells for predicting the effectiveness of immune checkpoint inhibitors in esophageal cancer.

BACKGROUND: Immune checkpoint inhibitors (ICIs), including nivolumab, have been approved to treat esophageal cancer. However, these remedies are not fit for all patients with esophageal cancer; therefore, a predictive surrogate marker is needed to assess their effectiveness. CD103+CD8+ tumor-infiltrating lymphocytes, defined as tissue-resident memory T cells (TRM), are promising indicators of response to ICIs, but it remains to be elucidated. This study investigated the association between the efficacy of ICIs and TRM. METHODS: The relationships between TRM infiltrating esophageal cancer, clinicopathological features, and prognosis after nivolumab initiation were examined using immunostaining. Tissue samples were obtained from surgically resected specimens of 37 patients with esophageal cancer who received nivolumab as a secondary or subsequent therapy. In addition, TRM infiltration was compared with programmed death-ligand 1 (PD-L1) expression and blood count parameters as predictors of nivolumab effectiveness. RESULTS: TRM-rich patients had a significant survival benefit after nivolumab initiation (12-months overall survival 70.8% vs 37.2%, p = 0.0485; 12-months progression-free survival 31.2% vs 0%, p = 0.0153) and experienced immune-related adverse events more frequently than TRM-poor patients (6 vs 2 patients). TRM infiltration was weakly correlated with PD-L1 positivity (r = 0.374, p = 0.022), but TRM may indicate more sensitive response to ICIs than PD-L1 expression in this study. Some blood test parameters also weakly correlated with TRM but did not impact prognosis. CONCLUSIONS: TRM-rich patients have a favorable prognosis after nivolumab initiation. Our results suggest that TRM are vital for antitumor immunity and are a promising predictor of ICIs effectiveness.

Impact of oral statin therapy on clinical outcomes in patients with cT1 breast cancer.

PURPOSE: A previous meta-analysis examining the relationship between statin use and breast cancer reported that the inhibitory effect of statins on breast cancer may be more pronounced in early-stage cases. In this study, we aimed to investigate the effects of hyperlipidemia treatment at the time of breast cancer diagnosis and to examine its correlation with metastasis to axillary lymph nodes among patients with so-called cT1 breast cancer whose primary lesion was 2 cm or less and was pathologically evaluated by sentinel lymph node biopsy or axillary lymph node dissection. We also investigated the effects of hyperlipidemic drugs on the prognosis of patients with early-stage breast cancer. METHODS: After excluding cases that did not meet the criteria, we analyzed data from 719 patients who were diagnosed with breast cancer, with a primary lesion of 2 cm or less identified by preoperative imaging, and who underwent surgery without preoperative chemotherapy. RESULTS: Regarding hyperlipidemia drugs, no correlation was found between statin use and lymph node metastasis (p = 0.226), although a correlation was found between lipophilic statin use and lymph node metastasis (p = 0.042). Also, the disease-free survival periods were prolonged following treatment of hyperlipidemia (p = 0.047, hazard ratio: 0.399) and statin administration (p = 0.028, hazard ratio: 0.328). CONCLUSION: In cT1 breast cancer, the results suggest that oral statin therapy may contribute to favorable outcomes.

Prognostic significance of the Naples prognostic score in colorectal cancer patients undergoing curative resection: a propensity score matching analysis.

BACKGROUND: Systemic inflammation is recognized as a hallmark of cancer that contributes to tumor development and progression in various malignancies. The Naples prognostic score (NPS) was established as a prognostic indicator for colorectal cancer (CRC). This study aims to examine the predictive value of the NPS for survival in CRC patients undergoing curative resection by a propensity score matching (PSM) analysis. METHODS: A total of 533 CRC patients were enrolled in this study. Overall survival (OS) and disease-free survival (DFS) were compared between high-NPS and low-NPS groups. A time-dependent receiver operator characteristic (ROC) curve analysis was conducted to calculate the area under curve (AUC) of the NPS for OS. A multivariable Cox-proportional hazards regression analysis and PSM analysis were used to identify independent prognostic factors for OS and DFS. We compared the predictive value of the NPS to that of the neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), Onodera prognostic nutritional index (PNI), and controlling nutritional status score (CONUT) for OS. RESULTS: High-NPS was significantly associated with worse OS and DFS. After PSM, 123 patients were included in each group. A multivariate analysis revealed that Age ≥ 68, ASA-PS ≥ 3, high NPS and undifferentiated tumor type were independently associated with OS, while high NPS, advanced T and N stage were independently associated with DFS after PSM. The NPS had the greatest AUC for OS in comparison to the NLR, LMR, PNI and CONUT. CONCLUSIONS: We successfully validated the prognostic utility of the NPS for CRC patients after curative resection.

Risk factors of "loss of independence" in elderly patients who received gastrectomy for gastric cancer.

OBJECTIVE: The aim of this study was to clarify the risk of loss of independence (LOI) following gastrectomy in elderly patients with gastric cancer (GC). METHODS: In this prospective study, frailty was assessed preoperatively by a frailty index (FI) in 243 patients aged ≥ 65 years who underwent gastrectomy for GC between August 2016 and December 2020. Patients were assigned into two groups (high FI vs. low FI) to investigate frailty and the risk of LOI after gastrectomy for GC. RESULTS: Overall and minor (Clavien-Dindo classification [CD] 1, 2) complication rates were significantly higher in the high FI group, but the two groups had similar rates of major (CD ≥ 3) complications. The frequency of pneumonia was significantly higher in the high FI group. In univariate and multivariate analyses for LOI after surgery, high FI, older age (≥ 75 years), and major (CD ≥ 3) complications were independent risk factors. A risk score assigning 1 point for each of these variables was useful in predicting postoperative LOI (LOI: score 0, 7.4%; score 1, 18.2%; score 2, 43.9%; score 3, 100%; area under the curve [AUC] = 0.765.) CONCLUSIONS: LOI after gastrectomy was independently associated with high FI, older age (≥ 75 years), and major (CD ≥ 3) complications. A simple risk score assigning points for these factors was an accurate predictor of postoperative LOI. We propose that frailty screening should be applied for all elderly GC patients before surgery.

Predictive value of the Naples prognostic score on postoperative outcomes in patients with rectal cancer.

PURPOSE: The Naples prognostic score (NPS) is a prognostic index based on the nutritional and inflammatory status. However, its utility in predicting postoperative complications (POCs) has not been examined in rectal cancer (RC). We evaluated the predictive value of the preoperative NPS for POCs in RC. METHODS: We retrospectively analyzed 235 patients who underwent surgery for RC. The NPS was calculated based on serum albumin, serum total cholesterol, the neutrophil-to-lymphocyte ratio (NLR) and the lymphocyte-to-monocyte ratio (LMR). Severe POCs were defined as Clavien-Dindo classification grade ≥ III. The optimal cut-off value of the NPS was determined by a receiver operator characteristic (ROC) curve analysis. The NPS, NLR, LMR, platelet-to-lymphocyte ratio (PLR), C-reactive protein (CRP)-to-albumin ratio (CAR), Glasgow prognostic score (GPS), Onodera prognostic nutritional index (PNI) and controlling nutritional status score (CONUT) were investigated as inflammation-based and/or nutritional markers. Predictors of severe POCs were analyzed by logistic regression modeling. RESULTS: Severe POCs were observed in 64 patients (27.2%). Male sex, operation time (> 257 min), blood loss (≥ 30 mL), albumin (< 4.0 g/dL), CRP (≥ 1.0 mg/dL), total cholesterol (≤ 180 mg/dL), NPS (≥ 2), LMR (≥ 3.48), PLR (≥ 103.6), CAR (> 0.025), GPS (≥ 1), PNI (< 48.1) and CONUT (≥ 2) were significantly associated with severe POCs. The multivariate analysis revealed that male sex, operation time (> 257 min), and a high NPS (≥ 2) were independent predictors of severe POCs. The ROC curve analysis revealed that the NPS had the greatest predictive value among the inflammation-based and/or nutritional markers. CONCLUSION: The NPS is a valuable predictor of severe POCs in RC.

The Evaluation of Sarcopenia before Neoadjuvant Chemotherapy Is Important for Predicting Postoperative Pneumonia in Patients with Esophageal Cancer.

INTRODUCTION: Sarcopenia is often observed in patients with esophageal cancer (EC). However, the influence of sarcopenia during neoadjuvant chemotherapy (NAC) on complications has not been fully investigated. Thus, we aimed to investigate the best way of evaluating sarcopenia for predicting complications, especially postoperative pneumonia (PP), in patients with EC undergoing NAC and esophagectomy. METHODS: We retrospectively reviewed 113 patients. The skeletal muscle mass index (SMI) was evaluated by bioelectrical impedance analysis and/or computed tomography. Patients were diagnosed with sarcopenia at pre-NAC and preoperative timing. Different criteria were compared in terms of the predictability of PP. Next, we evaluated which factors were related to sarcopenia with the best PP predictability. RESULTS: Fifteen (13.2%) patients developed grade III or higher PP. Pre-NAC modified European Working Group on Sarcopenia in Older People (EWGSOP) criteria showed the highest sensitivity (100%) and acceptable specificity (75.8%) for predicting PP. Low pre-NAC body mass index and %VC were significantly associated with sarcopenia by the modified EWGSOP criteria. CONCLUSION: Pre-NAC sarcopenia by modified EWGSOP was a significant predictor of PP after esophagectomy. Appropriate interventions for these patients should be explored to prevent PP.

The Cancer Cachexia Index Can Be Used to Prognostically Predict Patients with Gastric Cancer Undergoing Gastrectomy.

INTRODUCTION: Cancer cachexia occurs in cancer patients more frequently as the cancer progresses, with a negative impact on treatment outcomes. In this study, we sought to clarify the clinical impact of a cancer cachexia index (CXI) in patients with gastric cancer (GC) undergoing gastrectomy. METHODS: Between January 2013 and December 2018, we reviewed data from 556 patients treated for GC at our hospital. CXI was calculated using skeletal muscle index (SMI), serum albumin, and neutrophil-lymphocyte ratios (NLR). Patients were divided into high (n = 414) or low CXI (n = 142) groups. We investigated the clinical impact of CXI in patients with GC undergoing gastrectomy. RESULTS: Multivariate analyses of 5-year overall survival (OS) and cancer-specific survival (CSS) rates indicated that a low CXI was independently associated with unfavorable outcomes for patients with GC. In multivariate analyses, SMI was independent predictor of OS but not CSS. NLR was not an independent predictor of either OS or CSS. Complication incidences (≥ Clavien Dindo 3) were non-significantly higher in the low (vs. high) CXI group. CONCLUSION: CXI was a more valuable prognostic biomarker when compared with SMI or NLR in GC patients undergoing gastrectomy. We suggest that patients with low CXI values should be given more comprehensive treatment, including exercise and nutritional therapy to improve clinical outcomes.

Impact of a circular powered stapler on preventing anastomotic leakage in patients with left-sided colorectal cancer: a retrospective study.

BACKGROUND: The powered circular stapler, which was developed with the aim of providing reliable and reproducible anastomosis, provides complete anastomosis, resulting in a reduced risk of anastomotic leakage. The aim of this study was to compare the incidence of anastomotic leakage between a conventional manual circular stapler (MCS) and the ECHELON CIRCULAR™ Powered Stapler (ECPS) in patients with left-sided colorectal cancer who underwent anastomosis with the double stapling technique. METHODS: A total of 187 patients with left-sided colorectal cancer who underwent anastomosis with the double stapling technique with a conventional MCS or the ECPS during surgery at Osaka City University Hospital between January 2016 and July 2022 were enrolled in this study. RESULTS: The incidence of anastomotic leakage in the ECPS group was significantly lower than that in the MCS group (4.4% versus 14.3%, p = 0.048). Furthermore, even after propensity score matching, an association was found between the use of the ECPS and a reduced incidence of anastomotic leakage. CONCLUSION: The ECPS has the potential to help reduce the rate of anastomotic leakage in left-sided colorectal surgery.

Efficacy of the polyglycolic acid sheet for preventing anastomotic leakage in double-stapling technique anastomosis for left-sided colon or rectal cancer surgery: a propensity score-matched study.

BACKGROUND: To prevent anastomotic leakage in patients with left-sided colorectal cancer who underwent double-stapling technique (DST) anastomosis, we investigated a new method: DST anastomosis with a polyglycolic acid (PGA) sheet. This procedure has been shown to have the potential to decrease the rate of anastomotic leakage. However, due to the small number of cases enrolled in our previous study, it was not possible to compare the outcomes of the new and conventional procedures. The aim of this study was to evaluate the effect of the PGA sheet on preventing anastomotic leakage in patients with left-sided colorectal cancer who underwent DST anastomosis by retrospectively comparing the anastomotic leakage rate between the PGA sheet and conventional groups. METHODS: A total of 356 patients with left-sided colorectal cancer who underwent DST anastomosis during surgery at Osaka City University Hospital between January 2016 and April 2022 were enrolled in this study. Propensity score matching was performed to reduce the confounding effects secondary to imbalances in the use of PGA sheets. RESULTS: The PGA sheet was used in 43 cases (PGA sheet group) and it was not used in 313 cases (conventional group). After propensity score matching, the incidence of anastomotic leakage in the PGA sheet group was significantly lower than that in the conventional group. CONCLUSION: DST anastomosis with PGA sheet, which is easy to perform, contributes to the reduction of anastomotic leakage rate by increasing the strength of the anastomotic site.

[Surgical Technique for Mesorectal Division in the Robotic Anterior Resection for Rectal Cancer].

Since April 2018, robot-assisted rectal resection has been approved as an insurance medical treatment, and robot- assisted rectal resection is rapidly becoming widespread. Even in robot-assisted laparoscopic surgery, mesorectal division is difficult in a narrow pelvic cavity. At the beginning of the operation, Vessel Sealer ExtendTM(price 89,250 yen)was used, but as the procedure became stable, the mesorectal division was started with bipolar forceps and monopolar scissors. The purpose of this study was to investigate the mesorectal division time and postoperative complications associated with changes in the procedure. 36 patients who underwent robot-assisted anterior resection for rectal cancer by the same surgeon from January 2019 to December 2021. We compared mesorectal division time and postoperative complication. Median operation time were 267 minutes, median console time were 132 minutes. There were no complications such as intestinal obstruction or anastomotic leakage. There was no difference in mesorectal division time time between Vessel Sealer groups and Scissors groups(14 min 55 sec vs 16 min 5 sec). The mesorectal division with bipolar forceps and monopolar scissors could be performed without extending the operation time, and could be performed with cost-benefit and safely.

[The Role of Cancer-Associated Fibroblasts in Modulating Tumor Immunity in Colorectal Cancer].

Cancer-associated fibroblasts(CAFs)remodel the extracellular matrix(ECM)and shape the tumor microenvironment (TME), resulting in immune escape and the promotion of tumor metastasis. Using an orthotopic tumor model of colorectal cancers(CRCs)in mice, we demonstrated that the single-cell RNA sequencing of orthotopic rectal tumors identified a subpopulation of CAFs that modulate the immune response. In this review, we report that understanding the role of CAFs in the TME concerning tumor immunity may lead to future avenues for CAF-targeted therapy.

[A Case of Advanced Recurrent Rectal Cancer Successfully Treated by Rechallenge Therapy with an Anti-Epidermal Growth Factor Receptor(EGFR)Drug].

The patient was a 75-year-old man who had undergone potentially curative surgery for Stage Ⅲb rectal cancer followed by resection of liver metastases. Two years after the resection of liver metastases, lung and remnant liver metastases were found. He received chemotherapy for unresectable metastatic tumors. Based on the findings of molecular and pathological examinations(RAS: wild type; BRAF: wild type; MSI: negative; HER2: negative), the following chemotherapy regimens were administered: first-line, FOLFIRI plus panitumumab(PANI); second-line, mFOLFOX6; third-line, trifluridine/tipiracil; fourth- line, regorafenib. After fourth-line treatment, he was judged to have disease progression due to the increase in his lung and liver metastases and the elevation of tumor markers. All standard regimens were refractory, but the Eastern Cooperative Oncology Group performance status was zero and a liquid biopsy for RAS still showed wild type. Therefore, rechallenge therapy with anti-epidermal growth factor receptor(EGFR)drugs, cetuximab(CET)and irinotecan(IRI), was administered 13 months after the final course of FOLFIRI plus PANI treatment. After 4 courses of CET plus IRI, the size of the 2 metastatic tumors markedly decreased and his tumor marker levels normalized.