Total Minimally Invasive Curative Staged Resections After Induction Systemic Therapy for Metastatic Rectal Cancer.

Background: Intensified systemic chemotherapy following minimally invasive surgery for patients with unresectable metastatic colorectal cancer is performed to achieve curative resection and improve quality of life. We report a case of initially unresectable rectal cancer with metastases treated with laparoscopic and thoracoscopic staged resections after triplet chemotherapy plus bevacizumab.

Case: A 71-year-old man was referred to our hospital to examine the cause of constipation.

Characterizing multi-PIK3CA mutations across cancer types: Toward precision oncology.

Background: PIK3CA mutations are implicated in various cancers, but the implications of multiple concurrent mutations and their orientations within the gene have not been fully explored.

Methods: In this study, we analyzed multi-PIK3CA mutations across a diverse pan-cancer cohort comprising 3564 tumors.

Results: Multi-PIK3CA mutations were present in 10.

A case of hyalinizing trabecular tumor of the thyroid: diagnostic significance of PAX8-GLIS3 fusion.

Background: Hyalinizing trabecular tumor (HTT) is an uncommon follicular cell-derived thyroid tumor classified as a low-risk neoplasm by the World Health Organization Classification of Tumors of Endocrine Organs, 5th edition. The PAX8-GLIS3 gene fusion is reportedly a pathognomonic genetic alteration of HTT.

Case Presentation: A 43-year-old Japanese female was incidentally discovered to have an 8-mm, well-defined, hypoechoic mass in the left lobe of the thyroid gland by ultrasound examination.

Next‑generation sequencing to identify genetic mutations in pancreatic cancer using intraoperative peritoneal washing fluid.

The efficacy of next-generation sequencing (NGS) of tumor-derived DNA from intraoperative peritoneal washing fluid (IPWF) of patients with pancreatic ductal adenocarcinoma (PDAC) who intend to undergo curative resection remains unclear. The aim of the present study was to evaluate whether genomic mutations in tumor-derived DNA from IPWF samples of patients with PDAC who intend to undergo curative resection could be detected using NGS. A total of 12 such patients were included in this study.

Salivary Duct Carcinoma Arising in the Submandibular Gland in a Patient with Neurofibromatosis Type 1.

A 71-year-old man with neurofibromatosis type 1 (NF1) presented to our department with a 1-week history of a painful mass in the left submandibular area. Computed tomography (CT) and magnetic resonance imaging revealed an irregular-shaped tumor with a diameter of 2.0 cm in the left submandibular gland and a metastatic lymph node with a diameter of 1.

High-grade Solid Pseudopapillary Neoplasms of the Pancreas: Distinct Clinicopathological Malignant Features With Intriguing Gene Alterations through a Comparison With the Conventional Type.

Pancreatic solid pseudopapillary neoplasm (SPN) is a low-grade malignant neoplasm with a good prognosis. Clinically aggressive SPNs have rarely been reported but have not been analyzed in detail. In this study, we referred to this highly malignant type of SPN as high-grade SPN (HG-SPN) and compared its clinicopathological and genetic characteristics with conventional SPN (C-SPN) using immunohistochemistry and gene panel analyses.

Germline BRCA2 variant with low variant allele frequency detected in tumor-only comprehensive genomic profiling.

Germline BRCA1/2 variants in comprehensive genomic profiling (CGP) often exhibit variant allele frequency (VAF) exceeding 50%. However, when genomic loss occurs at the ipsilateral allele, including the germline variant in tumor cells, the VAF is low. This case report presents a patient with uterine sarcoma with a pathogenic BRCA2 mutation and low VAF in tumor-only CGP, which was later identified as a germline variant.

BRCA1/2 reversion mutations in a pan-cancer cohort.

Tumor sensitivity to platinum (Pt)-based chemotherapy and poly(adenosine diphosphate ribose) polymerase (PARP) inhibitors is increased by homologous recombination deficiency-causing mutations; in particular, reversion mutations cause drug resistance by restoring protein function. Treatment response is predicted by breast cancer susceptibility gene 1/2 (BRCA1/2) mutations; however, BRCA1/2 reversion mutations have not been comprehensively studied in pan-cancer cohorts. We aimed to characterize BRCA1/2 reversion mutations in a large pan-cancer cohort of Japanese patients by retrospectively analyzing sequencing data for BRCA1/2 pathogenic/likely pathogenic mutations in 3738 patients with 32 cancer types.

Cancer gene analysis of liquid-based cytology specimens using next-generation sequencing: A technical report of bimodal DNA- and RNA-based panel application.

Background: As liquid-based cytology (LBC) specimens harbor high-quality DNA, genomic analysis using LBC specimens is beneficial for integrative diagnosis. This study aimed to clarify the feasibility of LBC specimens for a bimodal application of DNA- and RNA-based next-generation sequencing (NGS) panels.

Methods: LBC specimens were prepared from cultured human cancer HEC59 cells using commercially available fixatives (Cellprep, CytoRich Red, and SurePath solutions), and were subjected to NGS for a feasibility study.

Clinical predominance of whole-exome sequencing to evaluate microsatellite instability status.

The microsatellite instability (MSI)/mismatch repair (MMR) status is one of the critical genomic biomarkers for predicting patient response to immune checkpoint inhibitors (ICIs). In this study, we aimed to investigate the concordance among the MSIsensor score obtained from whole-exome sequencing (WES), which could be a futuristic clinical cancer sequencing method, using only tumor tissues, MSI-PCR results, and immunohistochemistry (IHC) results to analyze various solid cancer types. We first endeavored to set the cut-off value of MSIsensor to determine functional deficient mismatch repair (f-dMMR) status.

The DNA integrity number and concentration are useful parameters for successful comprehensive genomic profiling test for cancer using formalin-fixed paraffin embedded tissue.

The acquisition of high-quality biospecimens and the appropriate handling of these materials are indispensable for successful clinical sequencing. We developed a cancer clinical sequencing system targeting 160 cancer genes: PleSSision-Rapid. Through the PleSSision-Rapid system, we have analyzed DNA quality evaluated by DIN (DNA integrity number) with 1329 formalin-fixed paraffin embedded (FFPE) samples including 477 prospectively collected tissues for genomic test (P) and 852 archival samples after routine pathological diagnosis (A1/A2).

Tumor Burden Monitoring with Circulating Tumor DNA During Treatment in Patients with Esophageal Squamous Cell Carcinoma.

Background: To guide appropriate treatment strategy, an accurate tumor monitoring modality that reflects tumor burden during neoadjuvant treatment is required for esophageal squamous cell carcinoma (ESCC). We aimed to investigate the clinical utility of circulating tumor DNA (ctDNA) in plasma in patients who received neoadjuvant chemotherapy (NAC) followed by esophagectomy.

Patients And Methods: Longitudinally collected plasma samples for ctDNA combined with genomic DNA from primary lesions were obtained from patients with histologically confirmed ESCC who underwent NAC followed by subtotal esophagectomy.

Real-world application of next-generation sequencing-based test for surgically resectable colorectal cancer in clinical practice.

To evaluate the significance of next-generation sequencing-based gene panel testing in surgically resectable colorectal cancer by analyzing real-world data. A total of 107 colorectal cancer patients who underwent curative surgery were included, and correlations between next-generation sequencing data and clinicopathological findings were evaluated. More combination patterns in gene alteration were identified in advanced-stage tumors than in early-stage tumors.

Hybridisation chain reaction-based visualisation and screening for lncRNA profiles in clear-cell renal-cell carcinoma.

Background: Analysis of long noncoding RNA (lncRNA) localisation at both the tissue and subcellular levels can provide important insights into the cell types that are important for their function.

Methods: By applying new fluorescent in situ hybridisation technique called hybridisation chain reaction (HCR), we achieved a high-throughput lncRNA visualisation and evaluation of clinical samples.

Results: Assessing 1728 pairs of 16 lncRNAs and clear-cell renal-cell carcinoma (ccRCC) specimens, three lncRNAs (TUG1, HOTAIR and CDKN2B-AS1) were associated with ccRCC prognosis.

Elevation of the Prognostic Factor Plasma Fibrinogen Reflects the Immunosuppressive Tumor Microenvironment in Esophageal Squamous Cell Carcinoma.

Introduction: Despite previous reports on the clinical significance of plasma fibrinogen (FNG) levels as a prognostic indicator of ESCC, its underlying mechanism remains unclear. This study aimed to validate the prognostic impact of plasma FNG levels and clarify its relationship with primary tumors in patients with esophageal squamous cell carcinoma (ESCC).

Methods: The prognostic impact of FNG was evaluated in patients with ESCC who underwent esophagectomy between 2000 and 2019.

Unique characteristics of tertiary lymphoid structures in kidney clear cell carcinoma: prognostic outcome and comparison with bladder cancer.

Background: The aims of this study were (1) to clarify the impact of tertiary lymphoid structure (TLS) status on the outcome and immunogenomic profile of human clear cell renal cell carcinoma (ccRCC) and (2) to determine phenotypic differences in TLSs between different types of genitourinary cancer, that is, urinary ccRCC and bladder cancer.

Methods: We performed a quantitative immunohistological analysis of ccRCC tissue microarrays and conducted integrated genome mutation analysis by next-generation sequencing and methylation array analysis. Since the tumor immune microenvironment of ccRCC often differs from that of other cancer types, we analyzed the phenotypic differences in TLSs between ccRCC and in-house bladder cancer specimens.

The oligodendroglial histological features are not independently predictive of patient prognosis in lower-grade gliomas.

The relevance of oligodendroglial histological features to patient prognoses is controversial. 93 LrGGs resected for about 2 decades were re-assessed based on WHO2007 with special interest to pure oligodendroglial diagnosis (oligodendroglioma or anaplastic oligodendroglioma) and presence of CFO features. Those histological features, patients OS, and tumor chromosomal/genetic characteristics were correlated each other in each of the 3 IDH-1p/19q-based molecular groups.

First successful case of platinum-based chemotherapy for neuroendocrine prostate cancer with and alterations.

Introduction: Deoxyribonucleic acid repair gene mutations are now being studied in a variety of solid tumors, with the hope of predicting prognosis, pathogenesis, and treatment outcomes.

Case Presentation: We report the case of a Japanese patient with advanced castration-resistant prostate cancer who exhibited a prominent response to platinum therapy and had coexisting and mutations according to retrospective multigene panel analysis.

Conclusion: Through a review of clinical outcomes and genetic/pathologic profiling, the presented case provides insights into future management strategies based on the tumor genetic status.

Concordance analysis of microsatellite instability status between polymerase chain reaction based testing and next generation sequencing for solid tumors.

Various malignancies exhibit high microsatellite instability (MSI-H) or mismatch repair deficiency (dMMR). The MSI-IVD kit, a polymerase chain reaction (PCR)-based method, was the first tumor-agnostic companion diagnostic to detect MSI status in MSI-H solid tumors. Recently, next-generation sequencing (NGS), which can also detect MSI-H/dMMR, has been made clinically available; however, its real-world concordance with PCR-based testing of MSI-H/dMMR remains to be investigated.

Landscape of prognostic signatures and immunogenomics of the AXL/GAS6 axis in renal cell carcinoma.

Background: Cabozantinib is an oral tyrosine kinase inhibitor in renal cell carcinoma (RCC), whose targets include oncogenic AXL and unique ligand GAS6. Critical gaps in basic knowledge need to be addressed to devise an exclusive biomarker and candidate when targeting the AXL/GAS6 axis.

Methods: To clarify the effects of the AXL/GAS6 axis on RCC, we herein performed a large-scale immunogenomic analysis and single-cell counts including various metastatic organs and histological subtypes of RCC.

Profiling the inhibitory receptors LAG-3, TIM-3, and TIGIT in renal cell carcinoma reveals malignancy.

A cutting edge therapy for future immuno-oncology is targeting a new series of inhibitory receptors (IRs): LAG-3, TIM-3, and TIGIT. Both immunogenomic analyses and diagnostic platforms to distinguish candidates and predict good responders to these IR-related agents are vital in clinical pathology. By applying an automated single-cell count for immunolabelled LAG-3, TIM-3, and TIGIT, we reveal that individual IR levels with exclusive domination in each tumour can serve as valid biomarkers for profiling human renal cell carcinoma (RCC).

Germline Whole-Gene Deletion of FH Diagnosed from Tumor Profiling.

Hereditary leiomyomatosis and renal cell carcinoma (HL (RCC)) entails cutaneous and uterine leiomyomatosis with aggressive type 2 papillary RCC-like histology. HLRCC is caused by pathogenic variants in the FH gene, which encodes fumarate hydratase (FH). Here, we describe an episode of young-onset RCC caused by a genomic FH deletion that was diagnosed via clinical sequencing.