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Abstract Background Pulmonary giant cell carcinoma is one of the rare histological subtypes with pleomorphic, sarcomatoid or sarcomatous elements. The prognosis of patients with this tumor tends to be poor, because surgery, irradiation and chemotherapy are not usually effective. Case presentation We herein report a patient with pulmonary giant cell carcinoma with stage IV disease in whom aggressive multi-modality therapy resulted in a long-term survival. A 51-year-old male underwent an emergent operation with a partial resection of small intestinal metastases due to bleeding from the tumor. The patient also underwent a left pneumonectomy due to hemothorax as a result of the rapid growth of the primary tumor. Thereafter, two different regimens of chemotherapy and a partial resection for other site of small intestinal metastases and a splenectomy for splenic metastases were performed. The patient is presently doing well without any evidence of recurrence for 3 years after the initial operation. Conclusion This is a first report of a rare case with stage IV pulmonary giant cell carcinoma who has survived long-term after undergoing aggressive surgical treatment and chemotherapy.

Competing Interests: Y.K. is a member of Circulation Reports’ Editorial Team.

Retained placenta can lead to septic shock; however, sepsis-induced cardiomyopathy (SICM) due to retained placenta has not been reported previously. This report presents a rare case of SICM following septic shock due to retained placenta after miscarriage in a 40-year-old woman, accompanied by the "shark fin sign" on an electrocardiogram, a pattern typically linked to myocardial ischemia. She experienced ventricular tachycardia and required venoarterial extracorporeal membrane oxygenation; however, she was successfully treated. We also reviewed previous cases of shark fin sign in patients without myocardial infarction. A review showed that half of the cases experienced lethal arrhythmias, even without myocardial infarction.

Background: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has been used to diagnose and stage lung cancer. Acquire™ Pulmonary and Expect™ Pulmonary dedicated EBUS-TBNA needles were introduced as the Franseen and Lancet needles, respectively. It is still unclear whether the Franseen or Lancet needles yield a higher quality specimen especially focusing on next-generation sequencing-based molecular testing., Methods: A single-center, prospective study performed at the Chiba University Hospital randomly assigned patients to two groups: Group A, wherein the first and second EBUS-TBNA were performed using Lancet and Franseen needles, respectively, and Group B, wherein the first and second EBUS-TBNA were performed using Franseen and Lancet needles, respectively. Each specimen was compared and analyzed pathologically. The primary outcome was the histological tissue area except blood clot and the cellularity of each sample. We also examined the success rate of molecular testing., Results: Twelve patients who underwent EBUS-TBNA between November 2022 and February 2023 were enrolled in this study. The tissue area of the specimens obtained by the Franseen and Lancet needles was 13.3 ± 6.4 mm2 and 10.6 ± 6.3 mm2, respectively (P = .355). The tumor cellularity in the specimens obtained using the Franseen and Lancet needles was 54.0 ± 30.3 and 46.2 ± 36.3%, respectively (P = .608). The success rate of molecular testing using the single-pass sample by Franseen needle was 85.7 and 57.1% by Lancet needle. No serious complications were reported., Conclusions: The Franseen needle tended to show a greater amount of specimen with higher tumor cellularity than the Lancet needle which may contribute higher success rate of molecular testing. Further studies must be conducted to validate the results of this study., Key Findings: What is known and what is new?  What is the implication, and what should change now?, (© The Author(s) 2024. Published by Oxford University Press.)

Background: This study aimed to investigate the utility of intensive triamcinolone acetonide (TA) injections after extensive esophageal endoscopic submucosal dissection (ESD)., Methods: This retrospective study included 27 lesions in 27 consecutive patients who underwent ESD (ulcers encompassing ≥3/4 of the esophageal circumference) and received TA injections without oral steroid administration. Groups A and B included patients undergoing ESD with and without complete circumferential resection, respectively. All patients received TA injections (100 mg/session) immediately after ESD. In Group A, weekly based TA injections were performed until near-complete ulcer epithelialization. In Group B, patients did not receive additional injections or received weekly or biweekly TA injections. The primary outcome was stricture rate, and the secondary outcomes were the proportion of patients requiring endoscopic balloon dilation (EBD) and the number of TA injections., Results: Group A included 7 lesions, and Group B included 20 lesions. The median (range) tumor lengths were 40 (30-90) and 45 (30-110) mm in Groups A and B, respectively. In Group A, the median circumferential resection diameter was 40 (20-80) mm. The stricture rate and the proportion of patients requiring EBD were 0 (0%) in Group A and 1 (5.0%) in Group B. The number of TA injection sessions was significantly higher in Group A than in Group B (8 [5-25] vs 1.5 [1-3]; p  < 0.001)., Conclusions: Intensive weekly or biweekly based TA injections might aid in preventing post-ESD stricture and the need for EBD in patients undergoing extensive resection involving the entire esophageal circumference.

We present the case of a 61-year-old man who developed nephrotic syndrome as a result of syphilis-associated secondary membranous nephropathy (MN). The patient showed nephrotic syndrome remission following antibiotic treatment for syphilis alone. Pathologically, the target antigen of immune complexes accumulated on glomerular basement membranes (GBM) in secondary MN caused by syphilis has been reported to be neuron-derived neurotrophic factor (NDNF). His renal histopathology was consistent with secondary MN caused by syphilis, with a full-house pattern on immunofluorescence microscopy, in addition to NDNF deposits that colocalized with IgG deposits granularly on the GBM. However, to date, there is no serological evidence for the involvement of NDNF in the GBM. In the present study, we found that anti-NDNF autoantibodies in the acute-phase serum disappeared in the convalescent-phase serum of a patient who recovered from syphilis and nephrotic syndrome after antibiotic therapy alone. This result supports the hypothesis that treatment of syphilis with antibiotics suppresses NDNF's antigenicity. In summary, we found new serological evidence emphasizing that NDNF is an etiological antigen in secondary MN caused by syphilis., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Keratins (KRTs) are intermediate filament proteins in epithelial cells, and they are important for cytoskeletal organization. KRT6A, classified as a type II KRT, is normally expressed in stratified squamous epithelium and squamous cell carcinomas. Little is known about the expression and role of KRT6A in adenocarcinomas. We investigated the clinicopathologic and molecular biological significance of KRT6A in colorectal adenocarcinoma. Immunostaining of colorectal adenocarcinoma cases treated at our institution demonstrated that KRT6A showed significantly stronger expression at the invasive front than that at the tumor center (P < .0001). The high KRT6A-expression cases (n = 47) tended to have a high budding grade associated with significantly worse prognoses. A multivariate analysis revealed that the KRT6A expression status was an independent prognostic factor for overall survival (P = .0004), disease-specific survival (P = .0097), and progression-free survival (P = .0033). The correlation between KRT6A and patient prognoses was also validated in an external cohort from a published data set. To determine the function of KRT6A in vitro, KRT6A was overexpressed in 3 colon cancer cell lines: DLD-1, SW620, and HCT 116. KRT6A overexpression increased migration and invasion in DLD-1 but did not in SW620 and HCT116. In 3-dimensional sphere-forming culture, KRT6A expression enhanced the irregular protrusion around the spheroid in DLD-1. Our findings in this study indicated that KRT6A expression is a valuable prognostic marker of colorectal cancer and KRT6A may be involved the molecular mechanism in the progression of invasive areas of colorectal cancer., (Copyright © 2024 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)

Pancreatic ductal adenocarcinoma (PDAC) has a very poor prognosis. Neoadjuvant chemotherapy is an effective PDAC treatment option, but chemotherapy causes unfavorable side effects. Glucocorticoids (e.g., dexamethasone [DEX]) are administered to reduce side effects of chemotherapy for solid tumors, including pancreatic cancer. Glucocorticoids have both beneficial and detrimental effects, however. We investigated the functional changes and gene-expression profile alterations induced by DEX in PDAC cells. PDAC cells were treated with DEX, and the cell proliferation, migration, invasion, and chemosensitivity to gemcitabine (GEM) were evaluated. The results demonstrated decreased cell proliferative capacity, increased cell migration and invasion, and decreased sensitivity to GEM. A comprehensive genetic analysis revealed marked increases in ECM1 and KRT6A in DEX-treated PDAC cells. We evaluated the effects of ECM1 and KRT6A expression by using PDAC cells transfected with those genes. Neither ECM1 nor KRT6A changed the cells' proliferation, but each enhanced cell migration and invasion. ECM1 decreased sensitivity to GEM. We also assessed the clinicopathological significance of the expressions of ECM1 and KRT6A in 130 cases of PDAC. An immunohistochemical analysis showed that KRT6A expression dominated the poorly differentiated areas. High expressions of these two proteins in PDAC were associated with a poorer prognosis. Our results thus demonstrated that DEX treatment changed PDAC cells' functions, resulting in decreased cell proliferation, increased cell migration and invasion, and decreased sensitivity to GEM. The molecular mechanisms of these changes involve ECM1 and KRT6A, whose expressions are induced by DEX., (© 2024 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

A 73-year-old male was admitted because of recurrent syncope. He was diagnosed with transient bradycardia caused by a 2:1 atrioventricular block, and he underwent cardiac computed tomography (CT) using 320 detector-row CT to screen for coronary artery disease. Significant coronary artery stenosis was not detected, but diffuse late iodinate enhancement was found on the epi-myocardium and endo-myocardium of the interventricular septum, and endo-myocardium of the anterior and lateral left ventricular (LV) myocardium (LVM) on CT. The ejection fraction and global longitudinal strain (LS) of LVM were 53.97% and - 9.87% on CT. Apical sparing was present, meaning the LS of LV apical segments were preserved compared with basal segments on CT. Pathological findings of LVM demonstrated loss of myocardial cells and extra-cellular amyloid deposition on the direct fast scarlet staining. He was finally diagnosed with transthyretin amyloidosis., (© 2024. The Author(s).)

Background and Aims: There is no consensus on the effectiveness of prophylactic clipping after colonic cold snare polypectomy (CSP). This study aimed to evaluate the utility of prophylactic clipping in preventing delayed bleeding (DB) after colorectal CSP in patients on antithrombotic agents., Methods: We retrospectively recruited consecutive patients on antithrombotic agents who underwent colorectal CSP in Chiba University Hospital. The DB rate was compared between patients with and without prophylactic clipping., Results: The study included 133 patients (422 polyps) requiring prophylactic clipping and 85 patients (282 polyps) not requiring prophylactic clipping. There were no significant differences in DB and hematochezia rates between the groups. By weighted logistic regression analysis, the odds ratio of hematochezia was 0.557 (95% confidence interval, 0.225-1.378; P = .205) in patients without clipping compared to those with clipping., Conclusions: Prophylactic clipping may not be necessary to prevent DB after colorectal CSP in patients on antithrombotic agents., Competing Interests: Disclosure All authors disclosed no financial relationships., (Copyright © 2024 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background: Primary adrenal leiomyosarcoma is a rare and aggressive mesenchymal tumor derived from the smooth muscle wall of a central adrenal vein or its tributaries; therefore, tumors tend to invade the inferior vena cava and cause thrombosis. The great majority of tumors grow rapidly, which makes the disease difficult to diagnose in its early clinical stages and needs differentiation from adrenocortical carcinomas for the selection of chemotherapy including mitotane which causes adrenal insufficiency., Case Presentation: We presented two patients with adrenal leiomyosarcoma who were referred to our hospital with abdominal pain and harboring large adrenal tumors and inferior vena cava thrombosis. The endocrine findings, including serum catecholamine levels, were unremarkable. These two patients were considered clinically inoperable, and CT-guided core needle biopsy was performed to obtain the definitive histopathological diagnosis and determine the modes of therapy. The masses were subsequently diagnosed as primary adrenal leiomyosarcoma based on the histological features and positive immunoreactivity for SMA (smooth muscle actin), desmin, and vimentin., Conclusions: Adrenal leiomyosarcoma derived from the smooth muscle wall of a central adrenal vein or its tributaries is rare but should be considered a differential diagnosis in the case of nonfunctioning adrenal tumors extending directly to the inferior vena cava. CT-guided biopsy is considered useful for histopathological diagnosis and clinical management of patients with inoperable advanced adrenal tumors without any hormone excess., (© 2023. The Author(s).)

Patients with psoriasis vulgaris have a higher incidence of pemphigoid than the general population. However, there are only a few concise reports on the coexistence of generalized pustular psoriasis (GPP) and pemphigoid. The authors describe a rare case of the simultaneous development of GPP and pemphigoid with multiple autoantibodies (i.e., BP180-C-terminal, 200-kDa protein, and laminin 332 proteins) in a complete responder of immune checkpoint inhibitor (ICI) treatment for lung cancer. Anti-interleukin 17 inhibitors for the GPP and oral corticosteroids at 10 mg/day for the pemphigoid effectively achieved remission in both diseases. It may not be uncommon to detect multiple autoantibodies in patients with pemphigoid; however, the detection of autoantibodies to more than three antigens in a single patient is relatively rare. In the current patient, the severe inflammation of GPP might have generated multiple autoantibodies. In addition, although pembrolizumab achieved a complete response and was discontinued 9 months before the onset of GPP and pemphigoid, the ICI might have affected the development of the two diseases. This case report adds useful information to the limited knowledge regarding the coexistence of GPP and pemphigoid, and aids in a better understanding of the pathological mechanisms and treatment options for such patients. Furthermore, the possibility that more patients may develop multiple autoimmune and autoinflammatory diseases in the era of ICIs should be recognized., (© 2023 Japanese Dermatological Association.)

Background and Aims: This randomized controlled trial (RCT) was designed to evaluate the short-term outcomes of underwater endoscopic mucosal resection (UEMR) and endoscopic submucosal dissection (ESD) of 21-30 mm colonic polyps., Method: We conducted a single-center RCT. Patients diagnosed with suspected colorectal intramucosal carcinoma (21-30 mm and adaptable for both UEMR and ESD) were randomly assigned to the UEMR and ESD groups at a 1:1 ratio. The primary endpoint was the R0 resection rate. We independently performed one-sample tests against the set threshold for each treatment. The significance level was set at p = 0.224., Result: Eleven polyps each in the UEMR and ESD groups, respectively, were analyzed. The R0 resection rate (%) was 36 (95% confidence interval 11-69) and 100 (72-100) for UEMR and ESD, respectively, with a significant difference between the two groups (p = 0.002). The p-value against the set threshold for UEMR was 0.743, whereas that for ESD was < 0.001 (one-sample binomial test). The en bloc resection rates (%) were 82 (48-97) and 100 (72-100) for UEMR and ESD, respectively; however, no significant difference was observed (p = 0.167). The mean treatment time (min) was significantly shorter in the UEMR group (8 ± 6) than in the ESD group (48 ± 29) (p = 0.001)., Conclusion: ESD could achieve a high R0 resection rate, while the en bloc resection rate was comparable between the two treatment techniques with less burden on patients undergoing UEMR for 21-30-mm colorectal polyps., Clinical Trial Registration: The study was registered at the Japan Registry of Clinical Trial as jRCT1030210015 and jRCT1030210177., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Immunological abnormalities have been hypothesized as a pathogenesis of biliary atresia (BA). We previously investigated the frequency and function of circulating regulatory T-cells (Tregs) and reported no differences compared to controls. However, the local Treg profile remains uncertain. We aimed to investigate the frequency of Tregs in BA liver tissues., Methods: The number of lymphocytes, CD4 + cells, and CD4 + FOXP3 + Tregs infiltrating the portal tract and the percentage of Tregs among CD4 + cells of BA and control patients were visually counted. The correlation between these data and clinical indicators was also examined., Results: The number of lymphocytes, CD4 + cells, and CD4 + FOXP3 + Tregs was higher in the BA group. However, the percentage of Tregs among CD4 + cells was similar in both groups. Each parameter was correlated with serum γ-GTP, but there was no clear association with liver fibrosis, jaundice clearance, and native liver survival., Conclusion: The number of Tregs infiltrating the portal tract was higher in BA patients. However, the infiltration of lymphocytes was also generally increased. Tregs appear to be unsuccessful in suppressing progressive inflammation in BA patients, despite recruitment to local sites. Investigation of Treg function in the local environment is warranted., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives. The diversifying modalities of treatment for gastric cancer raise urgent demands for the rapid and precise diagnosis of metastases in regional lymph nodes, thereby significantly impact the workload of pathologists. Meanwhile, the recent advent of whole-slide scanners and deep-learning techniques have enabled the computer-assisted analysis of histopathological images, which could help to alleviate this impact. Thus, we developed a deep learning-based diagnostic algorithm to detect lymph node metastases of gastric adenocarcinoma and evaluated its performance. Methods. We randomly selected 20 patients with gastric adenocarcinoma who underwent surgery as definitive treatment and were found to be node metastasis-positive. HEMATOXYLIN-eosin (HE) stained glass slides, including a total of 51 metastasis-positive nodes, were retrieved from the specimens of these cases. Other slides with 776 metastasis-negative nodes were also retrieved from other twenty cases with the same disease that were diagnosed as metastasis-negative by the final pathological examinations. All glass slides were digitized using a whole-slide scanner. A deep-learning algorithm to detect metastases was developed using the data in which metastasis-positive parts of the images were annotated by a well-trained pathologist, and its performance in detecting metastases was evaluated. Results. Cross-validation analysis indicated an area of 0.9994 under the receiver operating characteristic curve. Free-response receiver operating characteristic curve (FROC) analysis indicated a sensitivity of 1.00 with three false positives. Further evaluation using an independent dataset also showed similar level of accuracies. Conclusion. This deep learning-based diagnosis-aid system is a promising tool that can assist pathologists involved in gastric cancer care and reduce their workload.

Background/aim: Small renal cell carcinomas (sRCC) have drastically increased in recent years. Considering that sRCC have heterogeneous biology, it would be clinically relevant if specific clinical or pathological parameters could predict sRCC metastasis. In the present study, we aimed to assess the clinicopathological factors of pathologic T1a RCC (pT1a RCC) with or without metastasis to explore factors predicting metastasis., Patients and Methods: The present study included 198 patients with pT1a RCC who underwent radical or partial nephrectomy at fifteen institutions belonging to the Japanese Society of Renal Cancer, between1985 and 2017. Clinicopathological parameters, including age, sex, tumour size, tumour side, histological subtype, histological nuclear grade, lymphovascular invasion, and histological growth patterns, were analysed., Results: Fuhrman grade 3 or 4 tumours and infiltrative tumour growth patterns were significantly higher in patients with metastasis than in those without. The most common site of synchronous metastasis was the bone in patients with pT1a RCC (65.4%), whereas for patients with post-surgery metachronous metastasis (46.2%), it was the lungs., Conclusion: Histological growth pattern and nuclear grade are vital for predicting metastasis in pT1a RCC, suggesting careful long-term follow-up for such patients., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Advances in whole-slide image capture and computer image analyses using deep learning technologies have enabled the development of computer-assisted diagnostics in pathology. Herein, we built a deep learning algorithm to detect lymph node (LN) metastasis on whole-slide images of LNs retrieved from patients with gastric adenocarcinoma and evaluated its performance in clinical settings., Methods: We randomly selected 18 patients with gastric adenocarcinoma who underwent surgery with curative intent and were positive for LN metastasis at Chiba University Hospital. A ResNet-152-based assistance system was established to detect LN metastases and to outline regions that are highly probable for metastasis in LN images. Reference standards comprising 70 LN images from two different institutions were reviewed by six pathologists with or without algorithm assistance, and their diagnostic performances were compared between the two settings., Results: No statistically significant differences were observed between these two settings regarding sensitivity, review time, or confidence levels in classifying macrometastases, isolated tumor cells, and metastasis-negative. Meanwhile, the sensitivity for detecting micrometastases significantly improved with algorithm assistance, although the review time was significantly longer than that without assistance. Analysis of the algorithm's sensitivity in detecting metastasis in the reference standard indicated an area under the curve of 0.869, whereas that for the detection of micrometastases was 0.785., Conclusions: A wide variety of histological types in gastric adenocarcinoma could account for these relatively low performances; however, this level of algorithm performance could suffice to help pathologists improve diagnostic accuracy., (© 2023. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Androgen deprivation therapy is given to suppress prostate cancer growth; however, some cells continue to grow hormone-independently as castration-resistant prostate cancer (CRPC). Sulfated glycosaminoglycans promote ligand binding to receptors as co-receptors, but their role in CRPC remains unknown. Using the human prostate cancer cell line C4-2, which can proliferate in hormone-dependent and hormone-independent conditions, we found that epidermal growth factor (EGF)-activated EGFR-ERK1/2 signaling via 3-O-sulfated heparan sulfate (HS) produced by HS 3-O-sulfotransferase 1 (HS3ST1) is activated in C4-2 cells under hormone depletion. Knockdown of HS3ST1 in C4-2 cells suppressed hormone-independent growth, and inhibited both EGF binding to the cell surface and activation of EGFR-ERK1/2 signaling. Gefitinib, an EGFR inhibitor, significantly suppressed C4-2 cell proliferation and growth of a xenografted C4-2 tumor in castrated mouse. Collectively, our study has revealed a mechanism by which cancer cells switch to hormone-independent growth and identified the key regulator as 3-O-sulfated HS., (© 2023. The Author(s).)

An improved reading agreement rate has been reported in version 2.1 (v2.1) of the Prostate Imaging and Reporting and Data System (PI-RADS) compared with earlier versions. To determine the predictive efficacy of bi-parametric MRI (bp-MRI) for biochemical recurrence (BCR), our study assessed PI-RADS v2.1 score and tumor location in Japanese prostate cancer patients who underwent radical prostatectomy. Retrospective analysis was performed on the clinical data of 299 patients who underwent radical prostatectomy at Chiba University Hospital between 2006 and 2018. The median prostate-specific antigen (PSA) level before surgery was 7.6 ng/mL. Preoperative PI-RADS v2.1 categories were 1-2, 3, 4, and 5 in 35, 56, 138, and 70 patients, respectively. Tumor location on preoperative MRI was 107 in the transition zone (TZ) and 192 in the peripheral zone (PZ). BCR-free survival was significantly shorter in the PZ group (p = 0.001). In the total prostatectomy specimens, preoperative PI-RADS category 5, radiological tumor location, pathological seminal vesicle invasion, and Grade Group ≥ 3 were independent prognostic factors of BCR. These four risk factors have significant potential to stratify patients and predict prognosis. Radiological tumor location and PI-RADS v2.1 category using bp-MRI may enable prediction of BCR following radical prostatectomy., (© 2023. The Author(s).)

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignant neoplasm with various morphologies. Recognition of histological patterns that can predict prognosis is important in pathological examination. Recently, the complex glandular pattern was defined as a morphology associating the poor prognosis in lung adenocarcinoma. We investigated the significance of the complex glandular pattern in PDAC by performing a retrospective analysis. Among 240 consecutive cases of conventional PDACs, 21 cases in which complex glandular pattern constituted >50 % of the total tumor volume (CG-PDACs) were identified. The prevalence of CG-PDAC was 8.8 % among all preoperative therapy-naïve and surgically resected conventional PDACs. Compared to the control PDACs (n = 95), the CG-PDACs were characterized by significantly higher prevalence of small- to medium-sized artery invasion (71.4 % vs. 14.7 %, p < 0.0001), intratumoral necrosis (59.1 % vs. 16.8 %, p < 0.0001), tumor budding (mean: 15.5 vs. 12.5 per 0.785 mm 2 , p = 0.04), significantly higher Ki67 proliferative index (mean: 75.0 % vs. 54.7 %, p < 0.0001), and the HNF1α-/KRT81+ (quasi-mesenchymal) immunophenotype (42.9 % vs. 19.0 %, p = 0.004). In Kaplan-Meier analyses, the CG-PDAC patients achieved significantly worse disease-free survival (DFS) and overall survival (OS) compared to the control PDAC patients; the respective median DFS and OS were 6.3 and 17.7 months for CG-PDACs, and 22.6 and 52.8 months for control PDACs. A multivariate Cox regression analysis showed that predominance of complex glandular pattern was an independent prognostic factor (hazard ratio: 2.95; 95 % confidence interval: 1.46-5.98; p = 0.003). Our results provide new insights into the complex glandular pattern in conventional PDACs as a novel and potentially useful prognostic factor., Competing Interests: Declaration of competing interest The authors have disclosed that there is no significant relationship with any commercial companies pertaining to this article., (Copyright © 2023. Published by Elsevier Inc.)

Background and Aims: Gastric submucosal tumors (SMTs) are treated or monitored according to GI stromal tumor guidelines, but the adequacy of the guidelines has not been thoroughly examined. We investigated the long-term course of gastric SMTs to determine the validity of guideline-based follow-up methods and the factors contributing to their size increase., Methods: This study included gastric SMTs diagnosed as GI mesenchymal tumors (GIMTs) by using EUS and followed up with EUS. The percentage and speed of GIMT enlargement and factors associated with the enlargement were investigated by using the Cox proportional hazards model., Results: From January 1994 to May 2022, a total of 925 gastric SMTs were evaluated with EGD, and 231 SMTs were diagnosed as GIMTs. Of the 231 GIMTs, 145 were examined by EUS more than twice and were followed up for >6 months. The mean ± standard deviation follow-up period was 5.20 ± 4.04 years (range, 0.5-17.3 years), with 39 (26.9%) of 145 GIMTs increasing in size with a mean doubling time of 3.60 ± 3.37 years. A multivariate analysis of factors influencing tumor growth revealed that irregular extraluminal borders were an increasing factor (hazard ratio, 3.65; 95% confidence interval, 1.26-10.52), initial tumor size ≤9.5 mm (hazard ratio, .23; 95% confidence interval, 0.07-0.77) was a nonincreasing factor, and GIMTs with calcification (n = 13) did not increase in size., Conclusions: Tumor growth in gastric GIMTs <9.5 mm in diameter and/or with calcification is rare. Follow-up intervals for these lesions could be extended., (Copyright © 2023 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background: This study aimed to investigate the validity of pathological diagnosis of early CRC (E-CRC) from the genetic background by comparing data of E-CRC to colorectal adenoma (CRA) and The Cancer Genome Atlas (TCGA) on advanced CRC (AD-CRC)., Methods: TCGA data on AD-CRC were studied in silico, whereas by next-generation sequencer, DNA target sequences were performed for endoscopically obtained CRA and E-CRC samples. Immunohistochemical staining of mismatch repair genes and methylation of MLH1 was also performed. The presence of oncogenic mutation according to OncoKB for the genes of the Wnt, MAPK, and cell-cycle-signaling pathways was compared among CRA, E-CRC, and AD-CRC., Results: The study included 22 CRA and 30 E-CRC lesions from the Chiba University Hospital and 212 AD-CRC lesions from TCGA data. Regarding the number of lesions with driver mutations in the Wnt and cell-cycle-signaling pathways, E-CRC was comparable to AD-CRC, but was significantly greater than CRA. CRA had significantly more lesions with a driver mutation for the Wnt signaling pathway only, versus E-CRC., Conclusions: In conclusion, the definition of E-CRC according to the Japanese criteria had a different genetic profile from CRA and was more similar to AD-CRC. Based on the main pathway, it seemed reasonable to classify E-CRC as adenocarcinoma. The pathological diagnosis of E-CRC according to Japanese definition seemed to be valid from a genetic point of view., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Ovarian germ cell tumors composed of numerous well-formed embryonal bodies have been described as exhibiting a "polyembryoma pattern." In addition, some germ cell tumors are occasionally concomitant with neoplastic vascular proliferation. These include angiosarcomas and the recently reported mediastinal vasculogenic mesenchymal tumors. A 9-yr-old Japanese girl underwent surgery for a right ovarian tumor. Histologically, the polyembryoma pattern, nongestational choriocarcinoma, and vasculogenic lesions characterized by a neoplastic repetition of embryonic vasculogenesis have been intermingled. The polyembryoma pattern consisted of numerous complete and incomplete embryonal bodies and glandular structures resembling adult-type and fetal-type intestines. Vasculogenic lesions were composed of variously developed neoplastic vessels within the myxomatous stroma, which extended well beyond one low-power (40×) microscopic field. We concluded that the vasculogenic lesion in our case was the ovarian counterpart of the mediastinal vasculogenic mesenchymal tumor. After the surgery, the patient was administered adjuvant chemotherapy and was alive with no evidence of recurrence or other malignancy at 28 mo postsurgery., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 by the International Society of Gynecological Pathologists.)

Tumor cell plasticity and tumor heterogeneity are involved in therapy resistance. Cancer stem cells (CSCs) refer to tumor cells that have the ability to self-renew, and generate the diverse cells that comprise the tumor and complicate tumor heterogeneity. In recent years, CSCs have been reported to emerge from non-CSCs, which is known as tumor cell plasticity; however, the mechanism has not been fully elucidated. The present study investigated tumor cell plasticity from the viewpoint of aldehyde dehydrogenase 1 family member A1 (ALDH1A1) activity, which is one of the markers of CSCs. In the endometrioid carcinoma cell line HEC-1B, the ALDH1A1-low population spontaneously yielded an ALDH1A1-high population, mimicking tumor cell plasticity, and it was revealed that the mixture of the ALDH1A1-high population with the ALDH1A1-low population sometimes accelerated the transition from an ALDH1A1-low to ALDH1A1-high population. Two distinct HEC-1B sublines were established. One of the two sublines accelerated such a transition and the other did not show such acceleration. In the former subline, the effect of the ALDH1A1-high population was abolished when the direct cell-cell contact between ALDH1A1-high and ALDH1A1-low populations was inhibited. By comparing the two sublines, the neuronal membrane glycoprotein M6-b (GPM6B) was identified as the candidate mediating tumor cell plasticity. GPM6B was expressed in the border of ALDH1A1-expressing tumor cells and non-expressing tumor cells in clinical samples of EC. Notably, knockout of GPM6B decreased ALDH1A1 expression, whereas its overexpression increased the expression of ALDH1A1, suggesting that GPM6B mediated the induction of ALDH1A1 and the plasticity of CSCs., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2022, Spandidos Publications.)

Background and Purpose: MR imaging can reflect the pathologic progression of carcinoma ex pleomorphic adenoma (CXPA). This study aimed to identify the imaging findings related to extracapsular invasion of CXPA. Additionally, the pathologic background of these findings was investigated., Materials and Methods: This retrospective study included 37 patients with histologically confirmed CXPA. Three radiologists independently evaluated whether the CXPA showed the following characteristic MR imaging findings: border, capsule, the corona sign on fat-saturated T2WI and contrast-enhanced fat-saturated T1WI, and the black ring sign. The corona sign appeared larger on fat-saturated and/or contrast-enhanced fat-saturated T1WI than on T1WI. The black ring sign was defined as an intratumoral nodule with a thick low-intensity rim on T2WI. Interreader agreement of the visual assessment was performed using κ analysis, and MR imaging and histopathologic findings were also correlated. Kaplan-Meier survival and the log-rank test were used to estimate the 3-year disease-free survival., Results: MR imaging findings, especially peritumoral findings, showed a significant difference between invasive and noninvasive CXPA. The reliability was poor for the border and capsule. In contrast, it was good for the corona sign on fat-saturated and contrast-enhanced fat-saturated T1WI and the black ring sign. Pathologically, the corona sign reflected the invasiveness of the tumor and inflammatory cells, while the black ring sign reflected hyalinization or fibrosis. The corona sign also showed a significant difference in the 3-year disease-free survival., Conclusions: MR imaging findings, including the corona and black ring signs, reliably differentiated invasive and noninvasive CXPA. The corona sign can be used as a prognostic factor for CXPA., (© 2022 by American Journal of Neuroradiology.)

POEMS syndrome is a rare monoclonal plasma cell disorder, with unique symptoms distinct from those of other plasma cell neoplasms, including high serum VEGF levels. Because the prospective isolation of POEMS clones has not yet been successful, their real nature remains unclear. Herein, we performed single-cell RNA-Seq of BM plasma cells from patients with POEMS syndrome and identified POEMS clones that had Ig λ light chain (IGL) sequences (IGLV1-36, -40, -44, and -47) with amino acid changes specific to POEMS syndrome. The proportions of POEMS clones in plasma cells were markedly smaller than in patients with multiple myeloma (MM) and patients with monoclonal gammopathy of undetermined significance (MGUS). Single-cell transcriptomes revealed that POEMS clones were CD19+, CD138+, and MHC class IIlo, which allowed for their prospective isolation. POEMS clones expressed significantly lower levels of c-MYC and CCND1 than MM clones, accounting for their small size. VEGF mRNA was not upregulated in POEMS clones, directly indicating that VEGF is not produced by POEMS clones. These results reveal unique features of POEMS clones and enhance our understanding of the pathogenesis of POEMS syndrome.

Background: With the evolution of personalized medicine in the field of oncology, which includes optimal treatment selection using next-generation sequencing-based companion diagnostic systems and tumor-agnostic treatments according to common biomarkers, a liver tumor biopsy technique that can obtain a sufficient specimen volume must be established. The current study aimed to evaluate the safety and availability of a liver tumor biopsy technique with multiple puncture sites made using a coaxial introducer needle and embolization with gelatin sponge particles., Methods: Patients with primary or metastatic liver cancer who underwent liver tumor biopsies with puncture tract embolization using gelatin sponge (Spongel ® ) from October 2019 to September 2020 were included in the study. The complication and diagnostic rates were evaluated, and whether the specimen volume was sufficient for Foundation ® CDx was investigated., Results: In total, 96 patients were enrolled in this analysis. The median total number of puncture times per patient was 3 (range 1-8). The pathological diagnostic rate was 79.2%. Using the FoundationOne ® CDx, specimens with a sufficient volume required for genomic medicine were collected in 84.9% of patients. The incidence rate of bleeding was 4.2% (n = 4), and only one patient presented with major bleeding requiring transfusion., Conclusions: Liver biopsy with puncture tract embolization using a gelatin sponge may be safe and effective for collecting specimens with a volume sufficient for modern cancer treatments., (© 2022. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Hypercoagulability associated with malignant tumors causes thrombosis, termed Trousseau's syndrome, but is rarely associated with benign gynecological tumors, such as myoma and adenomyosis. We herein report a 47-year-old Japanese woman with uterine adenomyosis who developed multiple cerebral infarcts during menstruation. Edoxaban was initially used for prevention but failed to prevent recurrence of thrombosis. However, hysterectomy and bilateral salpingo-oophorectomy resulted in the successful prevention of recurrence of cerebral infarct for five years without antiplatelet or anticoagulant agents. In our patient, the surgical removal of adenomyosis was highly effective for preventing thrombosis in a patient with adenomyosis.

Recent large-scale genetic studies have proposed a new genetic classification of diffuse large B-cell lymphoma (DLBCL), which is clinically and biologically heterogeneous. However, the classification methods were complicated to be introduced into clinical practice. Here we retrospectively evaluated the mutational status and copy number changes of 144 genes in 177 Japanese patients with DLBCL, using targeted DNA sequencing. We developed a simplified algorithm for classifying four genetic subtypes-MYD88, NOTCH2, BCL2, and SGK1-by assessing alterations in 18 representative genes and BCL2 and BCL6 rearrangement status, integrating the significant genes from previous studies. In our cohort and another validation cohort from published data, the classification results in our algorithm showed close agreement with the other established algorithm. A differential prognosis among the four groups was observed. The NOTCH2 group showed a particularly poorer outcome than similar groups in previous reports. Furthermore, our study revealed unreported genetic features in the DLBCL subtypes that are mainly reported in Japanese patients, such as CD5-positive DLBCL and methotrexate-associated lymphoproliferative disorders. These results indicate the utility of our simplified method for DLBCL genetic subtype classification, which can facilitate the optimisation of treatment strategies. In addition, our study highlights the genetic features of Japanese patients with DLBCL., (© 2021 British Society for Haematology and John Wiley & Sons Ltd.)

Background and Aim: Immune checkpoint inhibitors and their combination with other agents have recently been available in advanced hepatocellular carcinoma (HCC). Hence, a thorough understanding of the tumor microenvironment based on tumor samples is yet to be achieved. This study aimed to explore the tumor microenvironment in advanced HCC in terms of microsatellite instability-high (MSI-H) by using tumor samples from advanced HCC patients eligible for systemic therapy., Methods: MSI-H was assessed by polymerase chain reaction, and the expression of mismatch repair proteins, PD-L1, CD8, VEGF, and HLA-class1 was evaluated by immunohistochemistry. Whole-exome sequencing was performed for MSI-H tumor samples., Results: Of 50 patients, one (2.0%) was confirmed with MSI-H. In the MSI-H advanced HCC tumor, a high tumor mutation burden, infiltration of CD8 + lymphocytes, and low expression of VEGF were identified. Although PD-L1 expression was negative, there was shrinkage of tumor following pembrolizumab. However, another tumor nonresponsive to pembrolizumab was present simultaneously. Checking the Cancer Genome Atlas (TCGA) database, we found a similar case to this patient. The TCGA case had unique gene features of miR-21 and miR-155 overexpression and hypermethylation of the MSH2 gene., Conclusion: We identified a very small number of MSI-H cases in HCC using one tumor biopsy sample for each patient with advanced HCC. In addition, epigenetic aberrations possibly lead to MSI-H in HCC patients. Since different HCC clones might coexist in the liver, sampling from multiple tumors should be considered to clarify the true proportion of MSI-H in HCC and to analyze tumor microenvironments., (© 2021 The Authors. JGH Open published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

The genetic characteristics of Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) in the Japanese population is unclear. This study aims to investigate the genetic characteristics from nondysplastic BE (NDBE) to early EAC in Japan. Clinical information was collected. Moreover, the genetic profile of NDBE without concurrent dysplasia, early EAC, and surrounding BE were also investigated using endoscopic biopsy samples and formalin-fixed, paraffin-embedded specimens from Japanese patients by targeted next-generation sequencing. Immunohistochemical staining for p53 was also performed for EAC lesions. Targeted NGS was performed for 33 cases with 77 specimens. No significant difference exists in the NDBE group between the number of putative drivers per lesion in the short-segment Barrett's esophagus (SSBE) and long-segment Barrett's esophagus (LSBE) [0 (range, 0-1) vs. 0 (range, 0-1). p = 1.00]. TP53 putative drivers were found in two patients (16.7%) with nondysplastic SSBE. TP53 was the majority of putative drivers in both BE adjacent to EAC and EAC, accounting for 66.7% and 66.7%, respectively. More putative drivers per lesion were found in the EAC than in the NDBE group [1 (range, 0-3) vs. 0 (range, 0-1). p < 0.01]. The genetic variants of TP53 in the Japanese early EAC were similar to those in western countries. However, TP53 putative drivers were detected even in Japanese patients with nondysplastic SSBE. This is significant because such nondysplastic SSBE might have higher risk of progressing to high-grade dysplasia or EAC. The risks of progression may not be underestimated and appropriate follow-ups may be necessary even in patients with SSBE.Trial registration: This study was registered at the University Hospital Medical Information Network (UMIN000034247)., (© 2021. The Author(s).)