[A Case of MSI-High Sigmoid Colon Cancer in Which Long-Term Survival Was Achieved by Pembrolizumab for Recurrent Lesions Resistant to Conventional Chemotherapy].

The patient underwent sigmoidectomy with D3 lymph node dissection and partial bladder resection for sigmoid colon cancer(cT4bN1M0, cStage Ⅲa), after preoperative chemotherapy with mFOLFOX plus panitumumab, and FOLFOXIRI plus bevacizumab. Postoperative adjuvant chemotherapy was performed by 8 courses of CAPOX. He relapsed hilar lymph nodes and peritoneal dissemination after 13 months after surgery, he underwent resection of the recurrent lesions.

M2 tumor-associated macrophages resist to oxidative stress through heme oxygenase-1 in the colorectal cancer tumor microenvironment.

M2 tumor-associated macrophages (M2-TAMs) promote cancer cell proliferation and metastasis in the TME. Our study aimed to elucidate the mechanism of increased frequency of M2-TAMs infiltration in the colorectal cancer (CRC)-TME, focusing on the resistance to oxidative stress through nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. In this study, we evaluated the correlation between M2-TAM signature and mRNA expression of antioxidant related genes using public datasets, and the expression level of antioxidants in M2-TAMs by flow cytometry and the prevalence of M2-TAMs expressing antioxidants by immunofluorescence staining using surgically resected specimens of CRC (n = 34).

Short-term outcomes of neoadjuvant chemotherapy with capecitabine plus oxaliplatin for patients with locally advanced rectal cancer followed by total or tumor-specific mesorectal excision with or without lateral pelvic lymph node dissection.

Background: The standard strategy in Japan for locally advanced rectal cancer is total mesorectal excision plus adjuvant chemotherapy. However, large tumors significantly restrict pelvic manipulation of the distal side of the tumor during surgery;therefore, from an oncological point of view, it is better to shrink the tumor as much as possible preoperatively to optimize the circumferential resection margin. In recent years, advances in systemic chemotherapy have significantly improved the tumor reduction effect, enabling such drug therapy prior to surgery for locally advanced rectal cancer.

[Significance and Treatment Strategy of Glasgow Prognostic Score in High Risk Stage Ⅱ Colorectal Cancer].

In this study, we investigated the usefulness of Glasgow prognostic score(GPS)as a prognostic factor for Stage Ⅱ colorectal cancer, and the treatment strategy by individualizing adjuvant chemotherapy. We enrolled 86 patients with Stage Ⅱ primary colorectal cancer who underwent curative resection. This study examines the prognostic significance of clinicopathological factors and GPS, NLR, LMR, PLR.

SH2D4A downregulation due to loss of chromosome 8p is associated with poor prognosis and low T cell infiltration in colorectal cancer.

Background: Colorectal cancer (CRC) develops through chromosomal instability (CIN) or microsatellite instability (MSI) due to deficient mismatch-repair (dMMR). We aimed to characterise novel cancer-associated genes that are downregulated upon malignant transformation in microsatellite stable (MSS) CRCs, which typically exhibit CIN with proficient mismatch-repair (pMMR).

Methods: Comprehensive screening was conducted on adenomas, MSI/MSS CRCs and cell lines, followed by copy number analysis, and their genetic and prognostic relevance was confirmed in microarray and RNA-seq cohorts (n = 3262, in total).

The Expression of Immune Checkpoint Receptors and Ligands in the Colorectal Cancer Tumor Microenvironment.

Background/aim: The limited efficacy of immune checkpoint inhibitors in colorectal cancer (CRC) is likely due to immunosuppressive mechanisms including T cell exhaustion caused by inhibitory immune checkpoints in the tumor microenvironment.

Materials And Methods: We investigated the expression status of the inhibitory immune checkpoint receptors on tumor-infiltrating T cells and their ligands on tumor cells by flow cytometry and immunohistochemistry, using surgically-resected specimens of CRC.

Results: Flow cytometry analysis indicated that TIM-3, TIGIT, and PD-1 were expressed on tumor-infiltrating CD4+ (8.

Validation of Gene Expression-Based Predictive Biomarkers for Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer.

Background: Neoadjuvant chemoradiotherapy (nCRT) followed by surgery is widely used for patients with locally advanced rectal cancer. However, response to nCRT varies substantially among patients, highlighting the need for predictive biomarkers that can distinguish non-responsive from responsive patients before nCRT. This study aimed to build novel multi-gene assays for predicting nCRT response, and to validate our signature and previously-reported signatures in multiple independent cohorts.

Long-term Outcomes of Lower Rectal Cancer Patients Treated with Total Mesorectal Excision and Lateral Pelvic Lymph Node Dissection after Preoperative Radiotherapy or Chemoradiotherapy.

Objectives: The standard strategy for advanced rectal cancer (RC) is preoperative short-course radiotherapy (SCRT)/chemoradiotherapy (CRT) plus total mesorectal excision (TME) in Western countries; however, the survival benefit of adding chemotherapy to radiotherapy remains unclear. There is accumulating evidence that either SCRT/CRT or lateral pelvic lymph node dissection (LPND) alone may not be sufficient for local control of advanced RC. We herein retrospectively evaluated the clinical outcomes of patients who were treated by SCRT/CRT+TME+LPND, particularly focusing on the prognostic impact of lateral pelvic lymph node metastasis (LPNM).

Circulating tumor cells after neoadjuvant chemotherapy are related with recurrence in esophageal squamous cell carcinoma.

Background: Circulating tumor cells (CTCs) are known to be a systemic process of malignant progression of cancer cells and there is a possibility that analysis for CTCs as a liquid biopsy become predictive or prognostic tools for cancer patients.

Methods: In the present study with the novel CTCs detection system (Celsee system), we performed quantitative and qualitative analysis of CTCs in patients with esophageal squamous cell carcinoma (ESCC) receiving neoadjuvant chemotherapy (NAC) with 5FU + CDDP regimen. CTCs are defined as having both DAPI positive and CD45 negative.

Downregulation of PAICS due to loss of chromosome 4q is associated with poor survival in stage III colorectal cancer.

Phosphoribosylaminoimidazole carboxylase, phosphoribosylaminoimidazole succinocarboxamide synthetase (PAICS) encodes an enzyme that catalyzes de novo purine biosynthesis. Although PAICS has been implicated as a potential therapeutic target in several cancers, its clinical and prognostic significance in colorectal cancer (CRC) is not fully understood. To elucidate the roles of PAICS in CRC, we investigated PAICS expression in four cohorts consisting of a total of 1659 samples based on quantitative RT-PCR, microarray and RNA-seq analysis.

PD-L1 overexpression in EBV-positive gastric cancer is caused by unique genomic or epigenomic mechanisms.

Epstein-Barr virus-positive gastric cancer [EBV (+) GC] is a distinct GC subtype with unique genetic and epigenetic aberrations. Here, we examined resected GC samples and publicly available microarray data and The Cancer Genome Atlas (TCGA) database to identify the mechanism underlying overexpression of PD-L1 in EBV (+) GC. We found that high levels of PD-L1 overexpression in EBV (+) GC were caused by focal amplification of CD274.

[A Case of Pelvic Liposarcoma Resected by Hybrid Approach].

Surgical resection is the most effective treatment for liposarcoma, a retroperitoneal malignant soft tissue tumor, and a reliable negative margin is required because of the high risk of local recurrence. We reported a case of pelvic liposarcoma that could be resected by laparoscopic and transsacral hybrid approach. A 60's-man had a mixed liposarcoma occupying the right rear of the pelvis in the rectum.

Tn Antigen Expression Defines an Immune Cold Subset of Mismatch-Repair Deficient Colorectal Cancer.

Colorectal cancer (CRC) cells often express Tn antigen, a tumor-associated truncated immature O-glycan (GalNAcα-O-Ser/Thr) that can promote tumor progression. Immunotherapies against Tn antigen have been developed and are being evaluated in clinical trials. Tn antigen can also be considered a novel immune checkpoint that induces immunosuppressive signaling through glycan-biding lectins to lead effector T cell apoptosis.

ARID1A deficiency in EBV-positive gastric cancer is partially regulated by EBV-encoded miRNAs, but not by DNA promotor hypermethylation.

AT-rich interactive domain 1A (ARID1A), which is a tumor suppressor gene, is frequently mutated in Epstein-Barr virus-positive gastric cancer [EBV (+) GC]. While most ARID1A mutations in GC are truncating mutations, leading to loss of ARID1A protein expression, epigenetic modifications appear to contribute to ARID1A deficiency in EBV (+) GC harboring wild-type ARID1A. Based on the significant role of epigenetic modifications in EBV (+) GC that contributes to ARID1A deficiency, the methylation status of ARID1A was evaluated in EBV-infected cells and GC patients using a publicly available microarray and the Cancer Genome Atlas (TCGA) database.

Therapeutic potential of anti-VEGF receptor 2 therapy targeting for M2-tumor-associated macrophages in colorectal cancer.

Background: Although immunotherapy with immune checkpoint inhibitors (ICIs) has become a standard therapeutic strategy in colorectal cancer (CRC) exhibiting microsatellite instability-high, limited patients benefit from this new approach. To increase the efficacy of ICIs in CRC patients, it is crucial to control the function of immunosuppressive cells in the tumor microenvironment. M2-tumor-associated macrophages (TAMs) are key immunosuppressive cells and promote tumor growth, angiogenesis, and epithelial-mesenchymal transition.

Tuberculous peritonitis; The effectiveness of diagnostic laparoscopy and the perioperative infectious prevention: A case report.

Background: Tuberculous peritonitis (TBP) is uncommon in Japan, and its diagnosis with conventional methods is time taking and requires a high clinical index of suspicion. Laparoscopy with peritoneal biopsy is a tool for rapid and accurate diagnosis of TBP. However, few cases have mentioned the infectious control and prevention during the perioperative period.

Selective sensitivity of EZH2 inhibitors based on synthetic lethality in ARID1A-deficient gastric cancer.

Background: AT-rich interactive domain 1A (ARID1A) is a tumor suppressor gene that is frequently mutated in gastric cancer (GC). Although ARID1A mutations are not a druggable target for conventional treatments, novel therapeutic strategies based on a synthetic lethal approach are effective for ARID1A-deficient cancers. The histone methyltransferase EZH2 acts in a synthetic lethal manner in ARID1A-mutated ovarian cancer, although its role in GC remains unknown.

A TGFβ-Dependent Stromal Subset Underlies Immune Checkpoint Inhibitor Efficacy in DNA Mismatch Repair-Deficient/Microsatellite Instability-High Colorectal Cancer.

Patients with DNA mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) colorectal cancer represent a biomarker-defined population with distinct clinicopathologic features who are susceptible to immune checkpoint inhibitors (ICI). However, their survival outcomes vary considerably and nearly half of them exhibit primary resistance to current ICIs, suggesting substantial molecular heterogeneity even among tumors with dMMR/MSI-H. We conducted an extensive analysis of the tumor microenvironment (TME) using multiple transcriptomic, proteomic, and IHC cohorts of colorectal cancer, comprising 222 dMMR/MSI-H and 1440 MMR-proficient/microsatellite stable tumors.

[A Case of Rectovaginal Fistula after Rectal Cancer Surgery Cured with Estriol Vaginal Tablet and Vaginal Lavage].

Although rectovaginal fistula is a rare complication of rectal cancer surgery, it is usually difficult to cure with conservative treatment, and patients generally need surgical intervention. A woman in her 70s underwent laparoscopic low anterior resection with right lateral lymph node dissection for rectal cancer. On postoperative day(POD)6, she had an anastomotic leakage and received conservative treatment.

Higher modified Glasgow Prognostic Score and multiple stapler firings for rectal transection are risk factors for anastomotic leakage after low anterior resection in rectal cancer.

Objective: Anastomotic leakage (AL) is one of the most devastating complications of rectal cancer surgery. Not only does AL result in reduced quality of life, extended hospitalization and impaired defecatory function, it also has a high local recurrence rate. In this study, we investigated risk factors for AL as it may help to decrease its occurrence and improve patient outcomes.

A subset of patients with MSS/MSI-low-colorectal cancer showed increased CD8(+) TILs together with up-regulated IFN-γ.

A small subset of patients with proficient mismatch repair (pMMR)/microsatellite stable (MSS)-colorectal cancer (CRC) benefit from immunotherapy with anti-programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) blockade. Therefore, the aim of the current study was to evaluate the immune status of patients with pMMR/microsatellite instability-low (MSI-L)/MSS-CRC and deficient MMR (dMMR)/MSI-high (MSI-H)-CRC in order to identify responders to anti-PD-1/PD-L1 inhibitors. The current study used a dataset downloaded from The Cancer Genome Atlas (TCGA) as well as 219 clinical tissue samples to investigate the infiltrating grade of cluster of differentiation (CD) 4 and CD8 tumor infiltrating lymphocytes (TILs), the expression levels of PD-L1 and PD-L2, the interferon-γ (IFN-γ) and CD8 T effector gene signatures, and the phosphorylated signal transducer and activator of transcription 1 (p-STAT1) status in patients with pMMR/MSI-L/MSS-CRC and dMMR/MSI-H-CRC.