Search

Quantitative analysis in this special issue (Greenfield, Brown, & Du, 2021) showed that the COVID-19 pandemic has led most parents to report greater expectations for their children to help with family subsistence. This familistic development exemplifies the shifts in behavior and values predicted by Greenfield's Theory of Social Change, Cultural Evolution, and Human Development when survival concerns rise and the social world retracts. Here, we use qualitative analysis to uncover the psychological processes behind the quantitative shift. Our California sample consisted of 109 parents with at least one child between age 7 and 18 living at home during the pandemic when they answered the survey. Forty-six of these parents provided qualitative data concerning expectations for their children's household responsibilities during COVID-19. An open-ended question asked parents to explain why their expectations of their children to help around the house and to carry out self-maintenance had changed or remained the same. Prominent themes in the qualitative responses manifest a shift from a mindset found in a large-scale urban society toward that found in a small-scale subsistence community: Before the pandemic, parents focused on increasing their children's competitiveness in society through extracurricular activities like tutoring, but that transitioned into a focus on household duties such as cooking and cleaning. In some cases, this shift was linked to an increase in life satisfaction; in other cases, it was linked to a decline in life satisfaction.

Liquid-based cytology (LBC) has changed the landscape of gynaecological cytology. A growing demand exists for LBC in diagnostic cytology, particularly for ancillary testing, such as immunocytochemistry and molecular testing. Ancillary testing solely based on conventional preparation (CP) methods remains challenging. Recently, the increased demand for specialist testing and minimally invasive techniques, such as endoscopic ultrasonography fine-needle aspiration, to obtain cellular samples has led to an increasing demand for ancillary testing on cytology LBC supernatant, slides and cell block (CB). This facilitates the diagnosis and prognosis in cytology samples enabling personalized treatment. An understanding of the history and future prospects of LBC is crucial for its application in routine diagnostics by cytopathologists and cytotechnologists. In this review, we initiated an internet search using the keyword 'liquid-based cytology', and we conducted a literature review to discuss the usefulness of combined diagnosis of LBC and CP, immunocytochemistry and molecular testing and assessed the quality of nucleic acids in diagnostic LBC. High-quality and cell-rich diagnostic LBC surpassed the CP method alone in terms of reliability and versatility of ancillary testing in cytological diagnosis. Conclusively, diagnostic LBC lends itself to various new technologies and is expected to continue evolving with innovations in the future., (© 2024 John Wiley & Sons Ltd.)

Well-differentiated endometrioid carcinoma (EC) is a low-grade cancer with relatively indolent behavior. However, even with well-differentiated histology, it sometimes tends to invade extensively and shows metastatic potential, suggesting that this is a group of cancers with heterogeneous behavior. In contrast, due to its tendency for younger onset, the treatment strategy for EC frequently considers fertility preservation, highlighting the need for a more accurate evaluation of myometrial invasion through biopsy and imaging diagnostics. We previously reported the involvement of the CXCR4-CXCL12 and CXCL14 axes in EC invasion. Accordingly, we investigated whether CXCR4 expression could reflect invasive potential and explored its interaction with cancer-associated fibroblasts that produce chemokines in the tumor microenvironment. Immunohistochemical expression of CXCR4 was assessed in 71 cases of EC (14 of EC confined to the endometrium and 57 of myoinvasive EC), 6 cases of endometrial intraepithelial neoplasia, and 42 cases of noncarcinomatous conditions. CXCR4 expression was significantly higher in myoinvasive EC than in noncancerous conditions, endometrial intraepithelial neoplasia, and endometrium-confined EC. By univariate and multivariate analysis, CXCR4 expression significantly reflected myometrial invasion. CXCR4 expression in the biopsied and resected specimens correlated weakly positively. Invasion and wound-healing assays were performed culturing an EC cell line in a cancer-associated fibroblast-conditioned medium. The invasion and wound-healing potentials were dependent on CXCR4 and cancer-associated fibroblast. Our study demonstrated that CXCR4 expression is an independent factor in myometrial invasion and can support diagnostic evaluation before treatment in the biopsy sample., Competing Interests: S.S. was supported by the Fukuoka Foundation for Sound Health Cancer Research Fund and a grant-in-aid of the “FUKUOKA” OBGYN Researcher’s Charity Foundation Fund, JapanGrant. The remaining authors declare no conflict of interest., (Copyright © 2024 by the International Society of Gynecological Pathologists.)

We aimed to establish a useful molecular marker for differentiating between follicular thyroid carcinoma (FTC) and follicular adenoma (FA). RNA was extracted from the invasive front and paired tumor center tissues from three FTC cases using laser microdissection for cDNA microarray analysis, revealing high expression of gamma-glutamyl cyclotransferase (GGCT) in the invasive front. Subsequently, immunohistochemical (IHC) staining of GGCT was performed with formalin-fixed paraffin-embedded (FFPE) sections of FTC (n = 32), FA (n = 64), and follicular tumor of uncertain malignant potential (FT-UMP, n = 5). The GGCT expression score (range: 0-300) was calculated by multiplying the intensity score (0-3) and percentage of positive cells. The Ki-67 labeling index was also assessed in 20 FTC and 25 FA cases from the same cohort. The GGCT expression score was higher in FTC than in FA (118.5 ± 51.4 vs. 57.3 ± 34.7, P < 0.0001). With the GGCT expression score, using a cutoff value of 101.1, the differentiation between FTC and FA was possible with a sensitivity of 68.8 % and specificity of 87.5 % (AUC = 0.832). With the Ki-67 labeling index, applying a cutoff value of 4.0 %, the distinction between FTC and FA resulted in a sensitivity of 50.0 % and specificity of 80.0 % (AUC = 0.677). The GGCT expression score was positively related to the Ki-67 labeling index in the FTC cases. (Spearman's ρ = 0.5293, P = 0.0164). Therefore, GGCT is a potential marker for differentiating FTC from FA. The GGCT expression of FTC may be indicative of its invasive and proliferative activity., Competing Interests: Declaration of Competing Interest The authors have no conflicts to declare., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Objectives: In advanced left-sided colorectal cancer, cutting the root of the inferior mesenteric artery (IMA) branching from the aorta is recommended for complete lymph node dissection. However, this procedure sometimes causes severe complications. This study aimed to elucidate the lymph nodes' distribution around the IMA and identify the most critical sites for lymph node dissection., Methods: This study included 30 consecutive patients with left-sided colorectal cancer who underwent curative resection with main lymph node dissection in a single institution between January and June of 2022. The mesenteric sections (main lymph nodes, IMA, left colic artery [LCA], and inferior mesenteric vein) were removed from the surgically excised specimen. Subsequently, whole-tissue sections were prepared and stained with hematoxylin and eosin. The positional relationships between each blood vessel and respective lymph nodes were then assessed using the pathological findings., Results: The main lymph nodes were identified in 26 out of 30 patients. The total number of dissected lymph nodes per patient was 0-30 (average: 5.3), and the median distance from the IMA to the main lymph node was 7.61 mm (1.87-43.26 mm). Dividing the lymph nodes into segments, we found 18%, 46%, and 36% of the lymph nodes in the proximal, middle, and distal segments, respectively. Additionally, all lymph nodes were found outside of the IMA sheath surrounding each arterial wall., Conclusions: In left-sided colorectal cancer, the main lymph nodes are mostly located around the LCA bifurcation, which may be essential to ensure main lymph node dissection for advanced stage cases., Competing Interests: Conflicts of Interest There are no conflicts of interest., (Copyright © 2024 The Japan Society of Coloproctology.)

Background and Aims: Colorectal polyps resected by cold snare polypectomy (CSP) are rarely diagnosed as colorectal cancer (CRC). We aimed to investigate the prevalence, clinical features, and prognosis of patients with CRC resected by CSP., Subjects: Patients with colorectal polyps treated with CSP between 2018 and 2022 were enrolled and regularly followed up (median observation period: 30.6 months). Logistic regression analysis and decision tree analysis were employed to investigate the clinical features of the patients., Results: A total of 5,064 colorectal polyps from 2,530 patients were resected by CSP. Of these, 0.24% were diagnosed as CRC; however, no patients died due to CRC. eGFR was an independent risk factor for the presence of CRC (unit 10, OR 0.716, 95%CI 0.525-0.973, P=0.0323) and its optimal cut-off value was 59.9 mL/min/1.73 m 2 . The decision-tree analysis revealed that 2.03% of patients with creatinine ≥ 1.0 mg/dL had CRC., Conclusion: CRC was diagnosed in 0.24% of the polyps; however, no patients died due to CRC. eGFR <60 mL/min/1.73 m 2 and creatinine >1.0 mg/dL were associated with CRC. Thus, colorectal polyps should be carefully examined in patients with chronic kidney disease.

Y-box binding protein 1 (YBX1) promotes oncogenic transformation and tumor growth. YBX1 plays a role in regulation of cell cycle promotion via upregulation of cell cycle-related genes. In ovarian cancer, YBX1 also promotes tumor growth, but the mechanisms of YBX1 in cell growth and cell cycle in ovarian cancer remain not to be fully understood. Here, we investigated whether YBX1-dependent cancer cell proliferation was specifically associated with expression of cell cycle related genes in ovarian cancer. Protein and mRNA expression levels of YBX1 and cell cycle-related genes in ovarian cancer cell lines and tissues were determined by western blot analysis, immunohistochemical analysis and reverse transcription-quantitative PCR. Cell cycle analysis was performed by flow cytometry. Luciferase assay and Chromatin immunoprecipitation assay were used to investigate a transcriptional function of YBX1. YBX1 silencing induced marked growth suppression in 4 cell lines (group A), moderate suppression in 5 cell lines (group B), and no suppression in 3 cell lines (group C) among 12 ovarian cancer cell lines in culture. The YBX1 silencing induced cell cycle arrest at G 2 /M phase and suppressed expression of cyclin A1 gene in group A and B cell lines, but not in group C cell lines. Cyclin A1 silencing specifically suppressed cell proliferation in group A cell lines and partially in group B cell lines, but not at all in group C cell lines. YBX1 mRNA levels were significantly correlated with cyclin A1 mRNA levels in patients with high-grade serous carcinoma. Augmented YBX1 expression plays a key role in tumor growth promotion in ovarian cancer in its close association with cyclin A1., (© 2024. The Author(s).)

We present two critical cases of life-threatening postpartum hemorrhage (PPH) due to amniotic fluid embolism (AFE) complicated by disseminated intravascular coagulopathy (DIC). These cases are the first to show the effectiveness of resuscitative endovascular balloon occlusion of the aorta (REBOA) for patient survival. In Case 1, the patient, experiencing critical conditions with severe PPH and DIC despite conventional treatments, including rapid blood transfusion and fibrinogen concentrate, was air-transferred to our hospital, where REBOA was promptly employed before hysterectomy was completed. Case 2 involved an ambulance-transferred patient with massive PPH and DIC despite conventional treatments. Prehospital REBOA was performed to prevent cardiac arrest during transfer, and hysterectomy was performed in the hospital. Given the rapid deterioration associated with AFE, REBOA can serve as a bridge until complete hemostasis to maintain vital signs and control bleeding in patients unresponsive to standard therapies before hemostatic interventions or during transfer., (© 2024 Japan Society of Obstetrics and Gynecology.)

Undifferentiated carcinoma of the liver is a rare and difficult-to-detect form of primary liver cancer. We herein report the first case of undifferentiated carcinoma of the liver in a 70-year-old Japanese woman with primary biliary cholangitis. The patient was diagnosed with cStage IVA liver cancer (85 mm in diameter) and treated with hepatic arterial infusion chemotherapy, 30 Gy radiotherapy, and 11 courses of on-demand transarterial chemoembolization. Although the hepatic tumor had markedly shrunk (from 85 to 20 mm), the patient ultimately died 16 months after the diagnosis due to rapid growth of lymph node metastases.

N-myc downstream regulated gene 1 (NDRG1) is a member of the NDRG family, of which four members (NDRG1, NDRG2, NDRG3, and NDRG4) have been identified. NDRG1 is repressed by c-MYC and N-MYC proto-oncogenes. NDRG1 is translated into a 43 kDa protein that is associated with the regulation of cellular stress responses, proliferation, and differentiation. In this study, we aimed to clarify the relationship between progression of glioblastoma (GB) IDH-wildtype and NDRG1 expression in tumor cells. We assessed the expression of NDRG1 in 41 GBs using immunostaining and evaluated its prognostic significance. NDRG1 expression by GBs was evaluated using Histoscore, which showed high and low scores in 23 and 18 cases, respectively. NDRG1-positive cells were strongly expressed in Ki-67 labeled proliferating tumor cells and CD105 positive proliferating microvessels around the area of palisading necrosis. Statistical analyses showed lower survival rates in the high-score group than the low-score group (P < 0.01). This study indicated that overexpression of NDRG1 by GB reflects tumor angiogenesis and poor patient prognosis., (© 2024 Japanese Society of Neuropathology.)

Introduction: Postpancreaticoduodenectomy hemorrhage (PPH) is a serious complication. Fatty or nonfibrous pancreas, or both, is a risk factor for pancreatic fistula. This study assessed various prognostic factors for interventional procedures for PPH, also focusing on the degree of pancreatic fatty infiltration/fibrosis evaluated histopathologically., Material and Methods: The participants were 29 patients with PPH who underwent endovascular treatment from September 2001 to March 2020. Univariate analysis was performed to determine whether the histopathological degree of pancreatic fatty infiltration/fibrosis and other factors were associated with complications and mortality after endovascular treatment for PPH., Results: Of 39 treatment sessions overall, 38 (97%) achieved technical success and 34 (87%) had clinical success. In-hospital mortality occurred in five patients (17%). No association was found between the pancreatic fistula and the histopathological degree of pancreatic fatty infiltration/fibrosis. Fourteen patients with hemorrhagic shock before endovascular treatment included all five patients with in-hospital mortality, while the 15 patients without hemorrhagic shock survived (P = 0.017). A bleeding tendency was associated with complications after endovascular treatment for PPH (P = 0.033)., Conclusions: Although our results revealed no significant relation between the histopathological degree of pancreatic fatty infiltration/fibrosis and clinical success, including prognosis, endovascular treatment may be effective for PPH.

Background/aim: There are no established biomarkers for immune checkpoint inhibitors (ICI) in colorectal cancer (CRC) with microsatellite stability (MSS) or proficient mismatch repair (pMMR). Therefore, this study aimed to identify biomarkers for ICI benefit in patients with pMMR by analyzing the down-regulated DNA repair-related genes involved in highly immunogenic and immune responses, and comparing their expression levels and clinical features., Materials and Methods: Mismatch repair (MMR), tumor-infiltrating lymphocytes (TIL), and tumor mutation burden (TMB) were evaluated in 13 CRC cases and mRNA expression levels of 95 DNA repair-related genes were measured. DNA repair-related genes with reduced mRNA expression in the high immunogenicity and high immune response groups were identified. Then, the mRNA expression levels of the identified DNA repair-related genes were measured in 135 patients with CRC. Hierarchical cluster analysis was performed using the mRNA expression levels to compare the clinicopathological characteristics of each cluster., Results: ATR, LIG4, and RAD52 mRNA levels were significantly down-regulated in the high immunogenicity group. GADD45B, SMUG1, and XRCC6 mRNA levels were significantly down-regulated in the high immune response group. Cases in the cluster with reduced mRNA expression of the six genes were pMMR cases. CD8 mRNA expression level was higher in this cluster than in the other clusters., Conclusion: Decreased mRNA expression levels of ATR, LIG4, RAD52, GADD45B, SMUG1, and XRCC6 genes were associated with high cytotoxic T cell and TMB levels, suggesting that these genes could serve as biomarkers for ICI efficacy in pMMR cases., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: This study aimed to characterize intraductal papillary neoplasm of the bile duct (IPNB) in patients undergoing initial and recurrent surgical resection and to evaluate the appropriateness of surgical treatment strategies., Patients and Methods: This study included 14 patients who underwent liver resection for intrahepatic IPNB. We assessed intraoperative and postoperative clinicopathological factors in patients undergoing both initial and recurrent surgeries., Results: Four patients experienced recurrence after initial surgery; all underwent pancreaticoduodenectomy. Postoperative complications were classified as Clavien-Dindo Grade 1-2 in three patients and Grade IIIb in one patient. There were no in-hospital deaths., Conclusion: Pancreaticoduodenectomy for recurrent cases following hepatectomy for IPNB is considered safe within an acceptable range and contributes to a favorable long-term prognosis., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Hedgehog (Hh) signaling pathway dysregulation is involved in the pathogenesis of metabolic dysfunction-associated steatohepatitis, and the sonic Hh (SHh) protein, a pivotal molecule in the Hh pathway, is expressed in ballooned hepatocytes. The present study aimed to investigate the clinicopathological significance of SHh expression in steatohepatitic hepatocellular carcinoma (SH-HCC). Reverse transcription-quantitative polymerase chain reaction and immunohistochemistry were performed to examine SHh gene and SHh protein expression in SH-HCC. Additionally, patients with conventional HCC (C-HCC) were included in the control group. Comparisons of patient and tumor characteristics were also performed. The prevalence of SH-HCC was 3% in the whole cohort, and it was significantly associated with a high prevalence of diabetes mellitus. SHh mRNA was detected in all patients with SH-HCC, but not in 23% of patients with C-HCC. Notably, SHh mRNA expression was not significantly different between patients with SH-HCC and those with C-HCC; however, high SHh protein expression was significantly more frequent in SH-HCC patients than in those with C-HCC. Although the prognosis was not significantly different between the SH-HCC and C-HCC groups, high SHh protein expression was an independent poor prognostic factor for HCC. In conclusion, SHh could potentially serve as a therapeutic target for patients with HCC., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Kusano et al.)

Background: Immune checkpoint inhibitors (ICIs) are emerging treatments for advanced hepatocellular carcinoma (HCC); however, evidence has shown they may induce hyperprogressive disease via unexplained mechanisms., Methods: In this study, we investigated the possible stimulative effect of ICIs on programmed cell death-ligand 1 (PD-L1)-harboring liver cancer cells under immunocompetent cell-free conditions., Results: The sarcomatous HAK-5 cell line displayed the highest expression of PD-L1 among 11 human liver cancer cell lines used in this study. HLF showed moderate expression, while HepG2, Hep3B, and HuH-7 did not show any. Moreover, sarcomatous HCC tissues expressed high levels of PD-L1. We observed approximately 20% increase in cell proliferation in HAK-5 cells treated with anti-PD-L1 antibodies, such as durvalumab and atezolizumab, for 48 h compared with that of those treated with the control IgG and the anti-PD-1 antibody pembrolizumab. No response to durvalumab or atezolizumab was shown in PD-L1-nonexpressing cells. Loss-of-function and gain-of-function experiments for PD-L1 in HAK-5 and HepG2 cells resulted in a significant decrease and increase in cell proliferation, respectively. Phosphorylated receptor tyrosine kinase array and immunoprecipitation revealed direct interactions between PD-L1 and AXL in tumor cells. This was stabilized by extrinsic anti-PD-L1 antibodies in a glycosylated PD-L1-dependent manner. Activation of AXL, triggering signal relay to the Akt and Erk pathways, boosted tumor cell proliferation both in vitro and in xenografted tumors in NOD/SCID mice., Conclusion: Collectively, this suggests that anti-PD-L1 antibodies stimulate cell proliferation via stabilization of the PD-L1-AXL complex in specific types of liver cancer, including in HCC with mesenchymal components., Significance: Therapeutic anti-PD-L1 antibodies promote cell proliferation by stabilizing the PD-L1-AXL complex in PD-L1-abundant neoplasms, including in HCC with mesenchymal components. Such a mechanism may contribute to the development of hyperprogressive disease., (© 2023. Asian Pacific Association for the Study of the Liver.)

Viral double-stranded RNA (dsRNA) is sensed by toll-like receptor 3 (TLR3) and retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs), including melanoma differentiation-associated gene 5 (MDA5). MDA5 recognizes the genome of dsRNA viruses and replication intermediates of single-stranded RNA viruses. MDA5 also plays an important role in the development of autoimmune diseases, such as Aicardi-Goutieres syndrome and type I diabetes. Patients with dermatomyositis with serum MDA5 autoantibodies (anti-CADM-140) are known to have a high risk of developing rapidly progressive interstitial lung disease and poor prognosis. However, there have been no reports on the soluble form of MDA5 in human serum. In the present study, we generated in-house monoclonal antibodies (mAbs) against human MDA5. We then performed immunohistochemical analysis and sensitive sandwich immunoassays to detect the MDA5 protein using two different mAbs (clones H27 and H46). As per the immunohistochemical analysis, the MDA5 protein was moderately expressed in the alveolar epithelia of normal lungs and was strongly expressed in the cytoplasm of lymphoid cells in the tonsils and acinar cells of the pancreas. Interestingly, soluble MDA5 protein was detectable in the serum, but not in the urine, of healthy donors. Soluble MDA5 protein was also detectable in the serum of patients with dermatomyositis. Immunoblot analysis showed that human cells expressed a 120 kDa MDA5 protein, while the 60 kDa MDA5 protein increased in the supernatant of peripheral mononuclear cells within 15 min after MDA5 agonist/double-strand RNA stimulation. Hydrogen deuterium exchange mass spectrometry revealed that an anti-MDA5 mAb (clone H46) bound to the epitope (415QILENSLLNL424) derived from the helicase domain of MDA5. These results indicate that a soluble MDA5 protein containing the helicase domain of MDA5 could be rapidly released from the cytoplasm of tissues after RNA stimulation., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Tomoaki Hoshino has patent pending to Detecting soluble form of MDA5., (Published by Elsevier Ltd.)

Gastric-type mucinous carcinoma (GAS) of the uterine cervix is the most common adenocarcinoma that develops independently of human papillomavirus infection; it is typically diagnosed at an advanced stage and has a poorer prognosis than usual-type endocervical adenocarcinoma. Few studies have examined the molecular profile of GAS, but genetic alterations in TP53 and STK11 have been repeatedly reported. We analyzed the clinicopathological characteristics and molecular profile of GAS. Fresh-frozen tissue specimens and formalin-fixed paraffin-embedded (FFPE) tissues from 13 patients with GAS treated between January 2000 and December 2020 were analyzed. We performed next-generation sequencing on eight fresh-frozen GAS specimens using the Cancer Hotspot Panel v2 (cases 1-8) and the FoundationOne companion diagnostic (F1CDx) assay on six FFPE samples (cases 8-13). Seventy-four genomic alterations were identified in 42 genes. In order of frequency, TP53, ATRX, CDKN2A, KRAS, APC, and STK11 were altered in at least three cases. Targetable genomic alterations were identified in all six patients' specimens analyzed using the F1CDx assay. GAS harbors various genomic alterations associated with sustained activation of signaling pathways or cell cycle regulation in addition to abnormalities in TP53, and precision medicine based on molecular profiling will be necessary to overcome GAS.

Background: Complete resection of presacral epidermoid cysts is recommended due to the potential for infection or malignancy. Transsacral and transabdominal approaches have been used to treat presacral tumors. However, there are no standard surgical approaches to resection. We present the case of a presacral epidermoid cyst in an obese male patient who underwent laparoscopic transabdominal resection., Case Presentation: A 44-year-old man was referred to our hospital for treatment of a cystic tumor on the pelvic floor. Contrast-enhanced computed tomography revealed a 45 × 40-mm tumor on the left ventral side of the rectum, right side of the ischial spine, dorsal side of the seminal vesicles, and in front of the 5th sacrum. Enhanced magnetic resonance imaging revealed a multilocular cystic tumor with high and low signal intensities on T2-weighted images. The tumor was diagnosed as an epidermoid cyst. We considered the transsacral or laparoscopic approach and decided to perform a laparoscopic-assisted transabdominal resection since the tumor was in front of away from the sacrum, and a transsacral approach would result in a larger scar due to poor visibility from the thickness of the buttocks. The entire tumor was safely resected under laparoscopic guidance, because the laparoscopic transabdominal approach can provide a good and magnified field of view even in a narrow pelvic cavity with small skin incisions, allowing safe resection of the pelvic organs, vessels, and nerves while observing the tumor contour., Conclusions: The laparoscopic transabdominal approach is an effective method for treating presacral tumors in obese patients., (© 2024. The Author(s).)

Background/aim: Advancements in genetic analysis technologies have led to establishment of molecular classifications systems for primary liver cancers. The correlation between pathological morphology and genetic mutations in hepatocellular carcinoma (HCC) is becoming increasingly evident. To construct appropriate experimental models, it is crucial to select cell lines based on their morphology and genetic mutations. In this study, we conducted comprehensive genetic analyses of primary liver cancer cell lines and examined their correlations with morphology., Materials and Methods: Thirteen primary liver cancer cell lines established in our Department were investigated. Eleven cell lines were HCC cell lines, whereas 2 were combined hepatocellular-cholangiocarcinoma (CHC) cell line characteristics. Whole exome sequencing and fusion gene analyses were conducted using a next generation sequencing platform. We also examined correlations between cell mutations and morphological findings and conducted experiments to clarify the association between morphological findings and genetic alterations., Results: Mutations in TP53, HMCN1, PCLO, HYDIN, APOB, and EYS were found in 11, 5, 4, 4, 3, and 3 cell lines, respectively. CTNNB1 mutation was not identified in any cell line. The original tumor of four cell lines (KYN-1, KYN-2, KYN-3, and HAK-6) showed morphologically macrotrabecular massive patterns and these cell lines harbor TP53 mutations. Two cell lines (KYN-2 and KMCH-2) showed an extremely high tumor mutation burden. These two cell lines possess ultra-mutations associated with DNA repair and/or DNA polymerase., Conclusion: The study identified correlations between morphological findings and genetic mutations in several HCC cell lines. Cell lines with unique genetic mutations were found. This information will be a valuable tool for the selection of suitable experimental models in HCC research., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

BACKGROUND Tumor-induced osteomalacia (TIO) is a paraneoplastic syndrome caused by aberrant fibroblast growth factor-23 (FGF-23)-producing tumors. Early surgical resection is the optimal strategy for preventing TIO progression. Thus, tumor localization is a priority for successful treatment. A simple and safe examination method to identify functional endocrine tumors is essential to achieve better outcomes in patients with TIO. CASE REPORT A 64-year-old Japanese man with recurrent fractures, hypophosphatemia, and elevated alkaline phosphatase and FGF-23 levels (109 pg/mL) was admitted to our university hospital and was diagnosed with FGF23-related hypophosphatemic osteomalacia. Notably, the superficial dorsal vein in the patient's left foot exhibited a high FGF-23 level (7510 pg/mL). Octreotide and ¹⁸F-fluorodeoxyglucose (FDG) scintigraphy and systemic venous sampling revealed that the tumor in the third basal phalanx of the left foot was responsible for FGF-23 overproduction. Tumor resection resulted in a rapid decrease in serum FGF-23 levels and an increase in serum phosphorus levels. CONCLUSIONS Octreotide scintigraphy, FDG-positron emission tomography, and systemic venous sampling are the standard methods for localizing functional endocrine tumors. However, the limited availability and invasive nature of these examinations hinder effective treatment. Here, we highlight the importance of peripheral superficial blood sampling as an alternative to conventional systemic methods for confirming the presence of FGF-23-producing tumors. Clinicians should consider TIO as a potential cause of acquired hypophosphatemic osteomalacia. Furthermore, peripheral superficial vein blood sampling may be useful for confirming the localization of FGF-23-producing tumors.

Background/aim: Recently, vessels encapsulating tumor clusters (VETC) pattern and macrotrabecular massive (MTM) pattern of hepatocellular carcinoma (HCC) have been reported as aggressive histological types. These histological patterns showed an immunosuppressive tumor immune microenvironment (TIME). Since there have been no reports on the differences of these two subtypes simultaneously, this study examined the immunophenotypes and TIME of MTM-HCC and VETC-HCC immunohistochemically., Patients and Methods: Seventy-four cases of previously diagnosed HCC, including 32 MTM-HCCs, 21 VETC-HCCs, and 21 conventional HCCs, were enrolled in immunohistochemical analysis. We conducted immunohistochemical analysis., Results: We found that MTM-HCC showed less frequent expression of HepPar-1, which is one of the most common hepatocytic markers. In MTM-HCC, the frequency of high expression levels of Keratin19, carbonic anhydrase (CA) IX, and PD-L1 was higher compared to VETC-HCC and conventional HCC. PD-L1 expression was found in 34.4% of MTM-HCC, 0% of VETC-HCC, and 19.0% of conventional HCC. The rate of PD-L1 expression in MTM-HCC was significantly higher than the others (p=0.0015). PD-L1 expression was significantly associated with epithelial cell adhesion molecules and CA IX expression, which are representative markers of tumor stemness and hypoxic conditions, respectively. The CD8 infiltration in VETC-HCC was significantly lower than that in conventional HCC., Conclusion: MTM-HCC had different immunophenotypes and TIMEs compared to HCC with the VETC pattern. Although both had immunosuppressive TIME, the elements forming TIME were quite different. To enhance the immune checkpoint inhibitor efficacy, changing TIME from a suppressive to an active form is essential., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)