Oncologic Outcomes of Patients with Early-Stage Cervical Cancer after Minimally Invasive Radical Hysterectomy and Sentinel Lymph Node Biopsy.

Background: The sentinel lymph node is the first node that cancer cells reach when migrating from the primary site. However, oncological outcomes after sentinel lymph node biopsy (SNB) have not been reported for cervical cancer. In this study, oncological outcomes were compared between patients receiving SNB and pelvic lymphadenectomy (PLD) for early-stage cervical cancer. Methods: One hundred and four patients with clinical stage 1A2, 1B1, and 2A1 cervical cancer were included in this study. All patients underwent laparoscopic or robot-assisted radical hysterectomy with SNB or PLD. Fifty-two patients with tumors ≤2 cm underwent SNB. Disease-free survival (DFS) and overall survival (OS) were compared between the groups. Results: The median (interquartile range) tumor size was 12 (7-20) mm in the SNB group and 20 (13-25) mm in the PLD group. Lymph node metastasis occurred in one patient in the SNB group and in nine patients in the PLD group. The median follow-up periods were 42 (24-60) and 82 (19-101) months in the SNB group and PLD group, respectively. The 3-year DFS rates were 100% in SNB and 91.5% in PLD. The 3-year OS was 100% in both groups. Conclusions: SNB was sufficient in cervical cancer patients with tumors ≤2 cm, suggesting that PLD might not be necessary for these patients.

Glycolysis in gastrointestinal stromal tumor: a brief overview.

Gastrointestinal stromal tumor (GIST) is the most prevalent mesenchymal tumor of the digestive tract. Its growth is primarily influenced by mutations in KIT or PDGFRA. Surgery is the primary treatment option for GIST; however, KIT inhibitors, such as imatinib, are used for inoperable cases. Resistance to imatinib is an upcoming challenge, especially because the effectiveness of alternative drugs is limited. Enhancement of the glycolysis pathway in cancer cells has been identified as a key feature in cancer. This unique metabolic activity has implications on tumor growth, prognosis, and resistance to therapy, even in GIST. Members of the glucose transporter (GLUT) family (particularly GLUT-1) play a significant role in GIST progression and response to treatment. Diagnostic imaging using 18F-fluorodeoxyglucose positron emission tomography/computed tomography, which enables visualization of glucose metabolism, can aid in GIST diagnosis and risk assessment. The interplay between glycolysis and GIST can lead to the development of various therapeutic strategies, especially those involving glycolysis-related molecules, such as hexokinase and lactate dehydrogenase. However, further research is required to understand the full spectrum of glycolysis in GIST and its therapeutic potential. Herein, we present an exhaustive overview and analysis of the role of glycolysis in GIST, especially as a therapeutic target.

Baseline gut microbiota as a predictive marker for the efficacy of neoadjuvant chemotherapy in patients with early breast cancer: a multicenter prospective cohort study in the Setouchi Breast Project-14.

PURPOSE: Various studies have demonstrated the causal relationship between gut microbiota and efficacy of chemotherapy; however, the impact of gut microbiota on breast cancer has not been fully elucidated. This study aimed to evaluate the associations between the gut microbiota before neoadjuvant chemotherapy and its consequent efficacy in breast cancer. METHODS: This prospective observational study included patients who received neoadjuvant chemotherapy for primary early breast cancer at eight institutions between October 1, 2019, and March 31, 2022. We performed 16S rRNA analysis of fecal samples and α and ß diversity analyses of the gut microbiota. The primary endpoint was the association between the gut microbiota and pathological complete response (pCR) to neoadjuvant chemotherapy. RESULTS: Among the 183 patients, the pCR rate after neoadjuvant chemotherapy was 36.1% in all patients and 12.9% (9/70), 69.5% (41/59), and 29.6% (16/54) in those with the luminal, human epidermal growth factor receptor 2, and triple-negative types, respectively. The α diversity of the gut microbiota did not significantly differ between patients with pCR and those without pCR. Among the gut microbiota, two species (Victivallales, P = 0.001 and Anaerolineales, P = 0.001) were associated with pCR, and one (Gemellales, P = 0.002) was associated with non-pCR. CONCLUSION: Three species in the gut microbiota had potential associations with neoadjuvant chemotherapy efficacy, but the diversity of the gut microbiota was not associated with response to chemotherapy. Further research is needed to validate our findings.

Trends in patterns of treatment and survival of colorectal cancer patients using cancer registry data in Japan: 1995-2015.

Recent advances in treating colorectal cancer (CRC) have increased the importance of multidisciplinary treatment. This study aimed to clarify trends in the treatment and survival of CRC using population-based cancer registry data in Japan. We analyzed the survival of CRC cases diagnosed from 1995 through 2015 from a population-based cancer registry of six prefectures. The year of diagnosis was classified into five periods, and the trends in the detailed categorization of treatments and survival were identified. We calculated net survival and excess hazard of death from cancer using data on 256,590 CRC patients. The use of laparoscopic surgery has been increasing since 2005 and accounts for the largest proportion of treatment types in the most recent period. Net survival of CRC patients diagnosed after 2005 remained high for laparoscopic surgery and endoscopic surgery (endoscopic mucosal resection or endoscopic submucosal dissection). There was an upward trend in treatment with chemotherapy in addition to open and laparoscopic surgery. Using the excess hazard ratio at the regional stage since 2005, there has been a significant improvement in survival in the younger age group and the rectum cancer group. By type of treatment, there was a tendency toward significant improvement in the open surgery + chemotherapy group. We clarified the trends in treating CRC and the associated trends in survival. Continuous survey based on population-based data helps monitor the impact of developments in treatment.

A Rare Tumor of Intravascular Myopericytoma in the Right Renal Vein.

Myopericytoma, a perivascular myoid neoplasm, is commonly found in the dermis or subcutaneous tissues; however, its occurrence in visceral organs is unusual. Here, we present an extremely rare tumor of intravascular myopericytoma of the right renal vein. A 44-year-old man was incidentally diagnosed with a mass in the right kidney during a routine checkup. A nephrectomy was performed because the urologist suspected renal cancer. A gross examination of the resected specimen revealed a well-circumscribed brown mass in the renal hilum. Histologically, the tumor showed a concentric multilayered proliferation of spindle cells surrounding blood vessels. Immunohistochemical staining showed that the spindle-shaped tumor cells were negative for desmin but positive for α-smooth muscle actin and h-caldesmon, indicating their myoid nature. We confirmed that the tumor was located in the right renal vein because it was encased within a thick wall that was desmin-positive and contained elastic fibers, as shown by Elastica van Gieson staining. The patient was diagnosed with an intravascular myopericytoma of the right renal vein. There are several differential diagnoses for renal mesenchymal tumors, including angiomyolipoma. This emphasizes the importance of considering these uncommon tumors when examining nephrectomy specimens.

Creation and Validation of Patient-Derived Cancer Model Using Peritoneal and Pleural Effusion in Patients with Advanced Ovarian Cancer: An Early Experience.

Background: The application of personalized cancer treatment based on genetic information and surgical samples has begun in the field of cancer medicine. However, a biopsy may be painful for patients with advanced diseases that do not qualify for surgical resection. Patient-derived xenografts (PDXs) are cancer models in which patient samples are transplanted into immunodeficient mice. PDXs are expected to be useful for personalized medicine. The aim of this study was to establish a PDX from body fluid (PDX-BF), such as peritoneal and pleural effusion samples, to provide personalized medicine without surgery. Methods: PDXs-BF were created from patients with ovarian cancer who had positive cytology findings based on peritoneal and pleural effusion samples. PDXs were also prepared from each primary tumor. The pathological findings based on immunohistochemistry were compared between the primary tumor, PDX, and PDX-BF. Further, genomic profiles and gene expression were evaluated using DNA and RNA sequencing to compare primary tumors, PDXs, and PDX-BF. Results: Among the 15 patients, PDX-BF was established for 8 patients (5 high-grade serous carcinoma, 1 carcinosarcoma, 1 low-grade serous carcinoma, and 1 clear cell carcinoma); the success rate was 53%. Histologically, PDXs-BF have features similar to those of primary tumors and PDXs. In particular, PDXs-BF had similar gene mutations and expression patterns to primary tumors and PDXs. Conclusions: PDX-BF reproduced primary tumors in terms of pathological features and genomic profiles, including gene mutation and expression. Thus, PDX-BF may be a potential alternative to surgical resection for patients with advanced disease.

A Rare Solitary Fibrous Tumor of the Mesorectum: A Case Report.

Solitary fibrous tumors (SFTs) are rare tumors that predominantly occur in the mesorectum. Few case reports have been published on mesorectal tumors, and this is the seventh case report. A 49-year-old female patient presented with a hypervascularized mesorectal tumor discovered incidentally during a routine medical examination. Using preoperative three-dimensional computed tomography (3D-CT), we identified vessels originating from the superior rectal and lateral sacral arteries, which are important sources of nutrients, and performed the procedure safely and without bleeding. Considering the lack of preoperative diagnosis and rectal blood flow, high anterior resection was performed. The histopathological diagnosis confirmed SFT, and the patient is currently doing well with no recurrence. Although SFT of the mesorectum occurs infrequently, it should be included in the differential diagnosis. In addition, the usefulness of preoperative 3D-CT, including the arterial phase, has been emphasized in such cases. This is the seventh reported case of a rare SFT in the mesorectum. Currently, there is no literature highlighting the usefulness of 3D-CT for SFTs of the mesorectum. However, it is a valuable preparatory tool for preoperative evaluation.

Consistency between Primary Uterine Corpus Malignancies and Their Corresponding Patient-Derived Xenograft Models.

Patient-derived xenograft (PDX) models retain the characteristics of tumors and are useful tools for personalized therapy and translational research. In this study, we aimed to establish PDX models for uterine corpus malignancies (UC-PDX) and analyze their similarities. Tissue fragments obtained from 92 patients with uterine corpus malignancies were transplanted subcutaneously into immunodeficient mice. Histological and immunohistochemical analyses were performed to compare tumors of patients with PDX tumors. DNA and RNA sequencing were performed to validate the genetic profile. Furthermore, the RNA in extracellular vesicles (EVs) extracted from primary and PDX tumors was analyzed. Among the 92 cases, 52 UC-PDX models were established, with a success rate of 56.5%. The success rate depended on tumor histology and staging. The pathological and immunohistochemical features of primary and PDX tumors were similar. DNA sequencing revealed similarities in gene mutations between the primary and PDX tumors. RNA sequencing showed similarities in gene expressions between primary and PDX tumors. Furthermore, the RNA profiles of the EVs obtained from primary and PDX tumors were similar. As UC-PDX retained the pathological and immunohistochemical features and gene profiles of primary tumors, they may provide a platform for developing personalized medicine and translational research.

Trends in the stage distribution of colorectal cancer during the COVID-19 pandemic in Japan: a nationwide hospital-claims data analysis.

BACKGROUND: The COVID-19 pandemic has affected cancer care. The aim of this study was to clarify the trend of colorectal cancer (CRC) stage distribution in Japan during the COVID-19 pandemic. METHODS: In this retrospective study, we used an inpatient medical claims database established at approximately 400 acute care hospitals. From the database, we searched patients who were identified as having the main disease (using ICD-10codes [C18.0-C20]) between January 2018 and December 2020. A multivariate logistic regression analysis was used to determine the impact of the pandemic on CRC stage distribution each month, and the odds ratio (OR) for late-stage cancer was calculated. RESULTS: We analyzed 99,992 CRC patients. Logistic regression analysis, including the interaction term between increased late-stage CRC effect during the pandemic period and by each individual month, showed that the OR for late-stage CRC was highest in July during the pandemic, at 1.31 (95%CI: 1.13- 1.52) and also significantly higher in September at 1.16 (95%CI: 1.00- 1.35). CONCLUSION: We investigated the trend of CRC stage distribution during the COVID-19 pandemic using a nationwide hospital-claims database in Japan, and found that the proportion of early-stage cancers tended to decrease temporarily after the state of emergency declaration due to the COVID-19 pandemic, but the effect was only temporary.

Clinical Epidemiological Studies of Colorectal Cancer by Record Linkage of Cancer Registries and Biospecimen Data: A Systematic Review.

BACKGROUND: The incidence and prognosis of colorectal cancer are associated with lifestyle, family history, and genetic predisposition. Record linkage between cancer registries and biospecimen data would enable us to conduct clinical epidemiological studies on incidence or prognosis including genome information. In this study, we conducted a systematic review of clinical epidemiological studies of colorectal cancer using record linkage between cancer registries and biospecimen data and examined the possibilities for future use of this linkage. METHODS: We searched PubMed and Google Scholar for articles regarding cancer registries and biospecimen data use published before December 2021. Selected articles were summarized by cancer registry use, biospecimen use, exposure, outcome, informed consent, and participant numbers by study design and type of cancer registry. RESULTS: Of the 2,793 identified articles, 81 studies were included in this review. The most frequently used cancer registries and study design were site specific cancer registries and cohort studies. Most use of cancer registries was for patient selection in cohort studies and case selection in case-control studies. Most use of biospecimen data was for prognostic factors in cohort studies and risk factors in case-control studies. In site specific cancer registries for the examination of familial colorectal cancer, most use of biospecimen data is to examine genome mutation, expression, or deficiency. CONCLUSION: We suggest that record linkage between cancer registries and biospecimen data would enable the accurate capture of outcomes and detailed genome-environmental factors, and to conduct clinical epidemiological studies according to specific research questions and tailored study designs.

The Impact of FGFR3 Alterations on the Tumor Microenvironment and the Efficacy of Immune Checkpoint Inhibitors in Bladder Cancer.

BACKGROUND: Currently, only limited knowledge is available regarding the phenotypic association between fibroblast growth factor receptor 3 (FGFR3) alterations and the tumor microenvironment (TME) in bladder cancer (BLCA). METHODS: A multi-omics analysis on 389 BLCA and 35 adjacent normal tissues from a cohort of OMPU-NCC Consortium Japan was retrospectively performed by integrating the whole-exome and RNA-sequence dataset and clinicopathological record. A median follow-up duration of all BLCA cohort was 31 months. RESULTS: FGFR3 alterations (aFGFR3), including recurrent mutations and fusions, accounted for 44% of non-muscle invasive bladder cancer (NMIBC) and 15% of muscle-invasive bladder cancer (MIBC). Within MIBC, the consensus subtypes LumP was significantly more prevalent in aFGFR3, whereas the Ba/Sq subtype exhibited similarity between intact FGFR3 (iFGFR3) and aFGFR3 cases. We revealed that basal markers were significantly increased in MIBC/aFGFR3 compared to MIBC/iFGFR3. Transcriptome analysis highlighted TIM3 as the most upregulated immune-related gene in iFGFR3, with differential immune cell compositions observed between iFGFR3 and aFGFR3. Using EcoTyper, TME heterogeneity was discerned even within aFGFR cases, suggesting potential variations in the response to checkpoint inhibitors (CPIs). Among 72 patients treated with CPIs, the objective response rate (ORR) was comparable between iFGFR3 and aFGFR3 (20% vs 31%; p = 0.467). Strikingly, a significantly higher ORR was noted in LumP/aFGFR3 compared to LumP/iFGFR3 (50% vs 5%; p = 0.022). This trend was validated using data from the IMvigor210 trial. Additionally, several immune-related genes, including IDO1, CCL24, IL1RL1, LGALS4, and NCAM (CD56) were upregulated in LumP/iFGFR3 compared to LumP/aFGFR3 cases. CONCLUSIONS: Differential pathways influenced by aFGFR3 were observed between NMIBC and MIBC, highlighting the upregulation of both luminal and basal markers in MIBC/aFGFR3. Heterogeneous TME was identified within MIBC/aFGFR3, leading to differential outcomes for CPIs. Specifically, a favorable ORR in LumP/aFGFR3 and a poor ORR in LumP/iFGFR3 were observed. We propose TIM3 as a potential target for iFGFR3 (ORR: 20%) and several immune checkpoint genes, including IDO1 and CCL24, for LumP/iFGFR3 (ORR: 5%), indicating promising avenues for precision immunotherapy for BLCA.

Changes in salivary microbiota due to gastric cancer resection and its relation to gastric fluid microbiota.

Gastric cancer is one of the leading causes of death worldwide, and resections are performed to cure the disease. We have previously reported the changes in the gastric microbiota after gastric cancer resection, which may be associated with the oral microbiota; however, the changes in the oral microbiota remain uncharacterized. This study aimed to characterize the changes in the salivary microbiota caused by gastric cancer resection and to evaluate their association with the gastric fluid microbiota. Saliva and gastric fluid samples were collected from 63 patients who underwent gastrectomy before and after surgery, and a 16S rRNA metagenomic analysis was performed to compare the microbiota composition. The number of bacterial species in the salivary microbiota decreased, and the bacterial composition changed after the resection of gastric cancer. In addition, we identified several bacterial genera that varied significantly in the salivary microbiota, some of which also showed similar changes in the gastric fluid microbiota. These findings indicate that changes in the gastric environment affect the oral microbiota, emphasizing the close association between the oral and gastric fluid microbiota. Our study signifies the importance of focusing on the oral microbiota in the perioperative period of gastrectomy in patients with gastric cancer.

Intratumoral metabolic heterogeneity of colorectal cancer.

Although the metabolic phenotype within tumors is known to differ significantly from that of the surrounding normal tissue, the importance of this heterogeneity is just becoming widely recognized. Colorectal cancer (CRC) is often classified as the Warburg phenotype, a metabolic type in which the glycolytic system is predominant over oxidative phosphorylation (OXPHOS) in mitochondria for energy production. However, this dichotomy (glycolysis vs. OXPHOS) may be too simplistic and not accurately represent the metabolic characteristics of CRC. Therefore, in this review, we decompose metabolic phenomena into factors based on their source/origin and reclassify them into two categories: extrinsic and intrinsic. In the CRC context, extrinsic factors include those based on the environment, such as hypoxia, nutrient deprivation, and the tumor microenvironment, whereas intrinsic factors include those based on subpopulations, such as pathological subtypes and cancer stem cells. These factors form multiple layers inside and outside the tumor, affecting them additively, dominantly, or mutually exclusively. Consequently, the metabolic phenotype is a heterogeneous and fluid phenomenon reflecting the spatial distribution and temporal continuity of these factors. This allowed us to redefine the characteristics of specific metabolism-related factors in CRC and summarize and update our accumulated knowledge of their heterogeneity. Furthermore, we positioned tumor budding in CRC as an intrinsic factor and a novel form of metabolic heterogeneity, and predicted its metabolic dynamics, noting its similarity to circulating tumor cells and epithelial-mesenchymal transition. Finally, the possibilities and limitations of using human tumor tissue as research material to investigate and assess metabolic heterogeneity are discussed.

Tertiary lymphoid structure and neutrophil-lymphocyte ratio coordinately predict outcome of pembrolizumab.

Emerging evidence suggests that the presence of tertiary lymphoid structures (TLS) and neutrophil-lymphocyte ratio (NLR) in peripheral blood is associated with the treatment response to checkpoint inhibitors (CPIs), whereas there is limited knowledge regarding whether these factors reciprocally impact the treatment outcomes of CPIs in metastatic urothelial carcinoma (mUC). Herein, we investigated treatment outcomes of platinum-refractory mUC patients (50 cases with whole-exome and transcriptome sequencing) treated with pembrolizumab. The pathological review identified 24% of cases of TLS in the specimens. There was no significant difference in the NLR between the TLS- and TLS+ groups (p = 0.153). In the lower NLR group, both overall survival and progression-free survival were significantly longer in patients with TLS than in those without TLS, whereas the favorable outcomes associated with TLS were not observed in patients in the higher NLR group. We explored transcriptomic differences in UC with TLS. The TLS was comparably observed between luminal (20%) and basal (25%) tumor subtypes (p = 0.736). Exploring putative immune-checkpoint genes revealed that ICOSLG (B7-H2) was significantly increased in tumors with lower NLR. KRT expression levels exhibited higher basal cell markers (KRT5 and KRT17) in the higher NLR group and lower differentiated cell markers (KRT8 and KRT18) in patients with TLS. In conclusion, the improved outcomes of pembrolizumab treatment in mUC are restricted to patients with lower NLR. Our findings begin to elucidate a distinct molecular pattern for the presence of TLS according to the NLR in peripheral blood.

Transcriptional repressor GATA binding 1 (TRPS1) immunoexpression in normal skin tissues and various cutaneous tumors.

BACKGROUND: Transcriptional repressor GATA binding 1 (TRPS1) is a transcription factor recently shown to play a role in the development of breast and liver cancer. Here, we evaluate TRPS1 immunoexpression in normal skin tissues and various cutaneous tumors. METHODS: TRPS1 immunohistochemistry was performed in 109 cases of primary cutaneous tumors and 19 cases of metastatic carcinomas. TRPS1 expression was also evaluated in the normal skin tissues. RESULTS: The normal epidermis was TRPS1-. In contrast, the eccrine apparatus, epithelial compartment of the hair follicles, hair papilla, sebaceous glands, and anogenital mammary-like glands were TRPS1+. In primary cutaneous tumors, TRPS1 positivity varied in poroma (2/3), nodular hidradenoma (4/5), spiradenoma (4/4), cutaneous mixed tumor (5/5), trichilemmal cyst (7/8), proliferating trichilemmal tumor (1/3), pilomatricoma (9/9), sebaceoma (2/5), extramammary Paget disease (13/13), sebaceous carcinoma (2/2), actinic keratosis (3/10), Bowen disease (7/12), and squamous cell carcinoma (1/5) cases. All cases of seborrheic keratosis, basal cell carcinoma, Merkel cell carcinoma, and malignant melanoma were TRPS1-. All metastatic breast carcinoma cases (8/8) were highly positive for TRPS1, while all but one of the other metastatic tumor cases were TRPS1-. CONCLUSIONS: TRPS1 immunoexpression was observed in several skin appendages and cutaneous tumors.

Experimental Study of Warburg Effect in Keloid Nodules: Implication for Downregulation of miR-133b.

Background: A keloid is composed of several nodules, which are divided into two zones: the central zone (CZ; a hypoxic region) and the marginal zone (MZ; a normoxic region). Keloid nodules play a key role in energy metabolic activity for continuous growth by increasing in number and total area. In this study, we aimed to investigate the roles of the zones in the execution of the Warburg effect and identify which microRNAs regulate this phenomenon in keloid tissue. Methods: Eleven keloids from patients were used. Using immunohistochemical analysis, 179 nodules were randomly chosen from these keloids to identify glycolytic enzymes, autophagic markers, pyruvate kinase M (PKM) 1/2, and polypyrimidine tract binding protein 1 (PTBP1). Western blot and qRT-PCR tests were also performed for PKM, PTBP1, and microRNAs (miR-133b and miR-200b, c). Results: Immunohistochemical analysis showed that the expression of the autophagic (LC3, p62) and glycolytic (GLUT1, HK2) were significantly higher in the CZ than in the MZ. PKM2 expression was significantly higher than PKM1 expression in keloid nodules. Furthermore, PKM2 expression was higher in the CZ than in the MZ. However, PKM1 and PTBP1 expression levels were higher in the MZ than in the CZ. The qRT-PCR analysis showed that miR-133b-3p was moderately downregulated in the keloids compared with its expression in the normal skin tissue. Conclusions: The Warburg effect occurred individually in nodules. The MZ presented PKM2-positive fibroblasts produced by activated PTBP1. In the CZ, PKM2-positive fibroblasts produced lactate. MiR-133b-3p was predicted to control the Warburg effect in keloids.

Lymphatic Complications Following Sentinel Node Biopsy or Pelvic Lymphadenectomy for Endometrial Cancer.

Sentinel node biopsy (SNB) is performed worldwide in patients with endometrial cancer (EC). The aim of this study was to evaluate and compare the occurrence rate of lymphatic complications between SNB and pelvic lymphadenectomy (LND) for EC. The medical records of women who underwent SNB or pelvic LND for EC between September 2012 and April 2022 were assessed. A total of 388 patients were enrolled in the current study. Among them, 201 patients underwent SNB and 187 patients underwent pelvic LND. The occurrence rates of lower-extremity lymphedema (LEL) and pelvic lymphocele (PL) were compared between the patients who underwent SNB and those who underwent pelvic LND. The SNB group had a significantly lower occurrence rate of lower-extremity LEL than the pelvic LND group (2.0% vs. 21.3%, p < 0.01). There were no patients who had PL in the SNB group; however, 4 (2.1%) patients in the pelvic LND group had PL. The occurrence rates of lower-extremity LEL and PL were significantly lower in patients who underwent SNB than those who underwent pelvic LND. SNB for EC has a lower risk of lymphatic complications compared to systemic LND.

Metastasis Inhibition.

Cancer metastasis is a common biological phenomenon observed in malignant tumors that can lead to death in affected individuals [...].