Search

Background: Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5) is a cancer stem cell (CSC) marker of colorectal cancer and may be a CSC marker of other cancer types. Few studies have been conducted on LGR5 expression in extrahepatic cholangiocarcinoma (ECC)., Methods: We analyzed LGR5 expression using RNAscope, a highly sensitive RNA in situ hybridization technique. Fifty-three ECCs were selected from the medical archives at Shinshu University Hospital and analyzed using a tissue microarray. LGR5 expression levels were divided into expression and no expression groups. LGR5 expression and clinicopathological characteristics were analyzed., Results: Among 25 cases, no LGR5-positive dots were identified. Among 28 cases, some LGR5-positive dots were observed in carcinoma cells, together with a wide range of LGR5-positive cells. LGR5 expression was conspicuous in glandular duct formations. Well- to moderately differentiated types showed significantly higher LGR5 expression than the poorly differentiated type (p = 0.0268). LGR5 expression was associated with good overall survival (p = 0.0219) and good disease-free survival (DFS) (p = 0.0228). High LGR5 expression was associated with well- to moderately-differentiated types, indicating a favorable prognosis. In terms of DFS, multivariate analysis showed that high LGR5 expression was an independent favorable prognostic factor (p = 0.0397)., Conclusions: These findings suggest that LGR5 is a promising, novel prognostic marker., (© 2024. The Author(s).)

Lobular endocervical glandular hyperplasia (LEGH) may be a precursor lesion of gastric-type adenocarcinoma of the uterine cervix (GAS). However, the genetic mechanisms underlying its carcinogenesis remain unclear. To elucidate the oncogenic process from LEGH to GAS, we compared gene mutations in early-stage GAS and adjacent LEGH in the same case. Fresh-frozen tissue sections were obtained from a patient with Stage IB3 GAS and adjacent LEGH who had undergone hysterectomy. Using laser microdissection, we harvested the LEGH and GAS portions separately from these sections and extracted the genomic DNA. Somatic variant analysis using whole-exome sequencing used DNA from the normal myometrium as a reference sequence. Somatic variants involving amino acid substitutions were detected in 61 and 125 locations in LEGH and GAS, respectively. Seven variants were common in both lesions, of which the pathogenic variant was GNAS only (c.2531G>A, p.R844H), a mutation frequently reported in pancreatic and colorectal cancers. LEGH had no other pathogenic variants; another pathogenic variant in GAS was found only at the same amino acid site as GNAS (c.2530C>T, p.R844C). In the present case, LEGH and GAS shared the same pathogenic variant of GNAS, indicating that both lesions had a common origin. Furthermore, the current results showed that the second GNAS variant is associated with the progression of LEGH to GAS. Further studies are required to elucidate GAS's pathogenesis and biological characteristics., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 by the International Society of Gynecological Pathologists.)

Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5), a significant cancer stem cell marker in colorectal cancer (CRC), lacks lymph node (LN) expression studies. In this study, we identified LGR5 expression by RNAscope, a highly sensitive RNA in situ method, and analyzed its association with clinicopathological characteristics. Tissue microarrays were generated from primary tumors (PTs) and LN metastases in paraffin-embedded blocks of 38 CRC surgical resection materials. LGR5 expression by RNAscope was evaluated by dividing the expression levels into negative and positive expression. In all but two cases of LN metastasis, LGR5-positive dots were detected in tumor cells, and there was a wide range of LGR5-positive cells. More LGR5-positive dots were identified in the gland-forming region. Twenty-three cases were classified into a high LGR5-expression group, and 15 cases were classified into a low LGR5-expression group. In the high LGR5-expression group, the histological grade was lower than in the low LGR5-expression group (p = 0.0159), while necrosis was significantly more prevalent (p = 0.0326), and the tumor, node, metastasis stage was significantly lower (p = 0.0302). There was no association between LGR5 expression levels in LN metastases and LGR5 expression levels in PT tissue. LGR5 expression in LN metastases may influence prognosis. Further analysis may lead to new therapeutic strategies., (© 2024 The Authors. Pathology International published by Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.)

[Purpose] In gastric cancer patients, low muscle mass decreases overall survival and quality of life (QOL). Resistance exercise with leucine-enriched essential amino acid (LEAA) supplementation may prevent muscle mass loss. This study was aimed at determining whether resistance exercise with LEAA supplementation prevents muscle mass loss in post-gastrectomy patients. [Participant and Methods] We conducted a single-center, open-label, randomized controlled pilot trial. Ten participants who underwent gastrectomy were divided into two groups. The intervention group underwent resistance exercise at 70% of one repetition maximum and received a supplement of 3 g of LEAA twice daily for 15 days, while the control group received standard care. We compared changes in muscle mass, physical function (muscle strength and continuous walking distance), and QOL between the groups. [Results] We found good adherence and participation rates in both groups. We failed to detect a significant difference in muscle mass between the groups. The intervention group showed significant improvements in muscle strength and QOL, while the control group showed no significant changes. [Conclusion] We failed to detect a significant difference in muscle mass due to resistance exercise with LEAA supplementation in post-gastrectomy patients. However, resistance exercise with LEAA supplementation might be beneficial for muscle strength recovery and QOL improvements., Competing Interests: The authors declare that they have no competing interests., (2024©by the Society of Physical Therapy Science. Published by IPEC Inc.)

Background. Tumor budding is a poor prognostic factor in colorectal adenocarcinoma, but the underlying mechanism remains unclear. Interleukin-6 (IL6) is one of the main cytokines produced by cancer-associated fibroblasts. IL6 is linked with cancer progression and poor prognosis by activating cancer cells and modifying the cancer microenvironment. However, little is known about the expression of IL6 in tumor budding and its association with tumor budding in colorectal adenocarcinoma. Methods. The clinicopathological and prognostic significance of IL6 in tumor budding was examined using a tissue microarray consisting of 36 patient samples of tumor budding in colorectal adenocarcinoma. IL6 mRNA was detected by RNAscope. Patients were stratified into negative and positive IL6 expression groups. Results. IL6 expression was overwhelmingly observed in cancer stroma but was negligible in cancer cells. Tumor budding grade was higher in the IL6-positive group in cancer stroma than in the IL6-negative group ( P  = .0161), while the IL6-positive group significantly exhibited the epithelial-mesenchymal transition phenotype compared with the IL6-negative group in cancer stroma ( P  = .0301). There was no significant difference in overall survival between colorectal adenocarcinoma patients in the IL6-positive and -negative groups in cancer stroma. Conclusion. Tumor budding may be affected by IL6 expression, and IL6 expression in cancer stroma at tumor budding may be an important prognostic marker., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Perioperative factors are useful for predicting postoperative infectious complications (PIC) in gastric cancer. Specifically, postoperative inflammatory response indicators (PIRI), [C-reactive protein (CRP) level, body temperature (BT), and white blood cell (WBC) count], are widely used in clinical practice. We investigated predictive factors for PIC, including PIRI, to establish a simple and practical indicator of postoperative complications after gastrectomy., Methods: We retrospectively collected clinical data from 200 patients with fStage I-III gastric cancer. Univariate/multivariate analysis was performed to evaluate the relationship of predictive factors [host factors, clinicopathological factors, and PIRI (BT, WBC count, and CRP level on postoperative day (POD) 1 and 3) ]. Cut-off values of the predictive factors were analyzed using receiver operating characteristic (ROC) curve modulated by the presence/absence of PIC Grade II, III (Clavien-Dindo classification)., Results: Age [Odds ratio (OR): 5.67], smoking history (OR: 3.51), and CRP level (OR: 5.65), WBC count (OR: 8.96), and BT (OR: 3.37) on POD3 were selected as independent factors from multivariate analysis. Cut-off values were 77 years, 14.8 mg/dL, 116.0×10 2 /μL, and 37.4°C, respectively., Conclusions: Predictive factors relative to PIC in gastric cancer were CRP level ≥ 14.8 mg/dL, WBC count ≥ 116.0×10 2 /μL, and BT ≥ 37.4°C all on POD3. Age ≥ 77 years, and history of smoking were relative to PIC, suggesting a simple and practical indicator applicable in clinical practice.

Background: IgG4, which plays a pivotal role in the progression of phenotypically diverse tumors, serves as a prognostic marker because of its influence on cancer immunity. Nevertheless, the functions of IgG4 in tongue squamous cell carcinoma (TSCC) remained to be identified., Methods: To evaluate the significance of IgG4 expression in TSCC, we performed immunohistochemical analysis of patients with TSCC (n = 50) to evaluate the correlation of IgG4 expression with patients' clinicopathological features and prognoses., Results: Higher IgG4 expression detected in TSCC tissues was associated with the less advanced mode of invasion (Yamamoto-Kohama [YK] 1-3) (P = 0.031) and with well-differentiated TSCC (P = 0.077). Kaplan-Meier analyses revealed that the higher IgG4 expression group exhibited better prognosis indicated by overall survival (OS) (P = 0.04) and recurrence-free survival (RFS) (P = 0.016). Univariate analysis of OS indicated that IgG4 expression was associated with longer OS (P = 0.061), and multivariate analysis of RFS revealed that IgG4 expression served as an independent prognostic factor for longer RFS (P = 0.005)., Conclusion: These results indicate that relatively higher IgG4 levels serve as a favorable prognostic factor for TSCC., (© 2024. The Author(s).)

Objective. The prostate moves in accordance with the movement of surrounding organs. Tumor position can change by ≥3 mm during radiotherapy. Given the difficulties of visualizing the prostate fluoroscopically, fiducial markers are generally implanted into the prostate to monitor its motion during treatment. Recently, internally motion guidance methods of the prostate using a 99.5% gold/0.5% iron flexible notched wire fiducial marker (Gold Anchor® , Naslund Medical AB, Huddinge, Sweden), which requires a 22 gauge needle, has been used. However, because the notched wire can retain its linear shape, acquire a spiral shape, or roll into an irregular ball, detecting it on fluoroscopic images in real-time incurs higher computation costs. Approach. We developed a fiducial tracking algorithm to achieve real-time computation. The marker is detected on the first image frame using a shape filter that employs inter-class variance for the marker likelihood calculated by the filter, focusing on the large difference in densities between the marker and its surroundings. After the second frame, the marker is tracked by adding to the shape filter the similarity to the template cropped from the area around the marker position detected in the first frame. We retrospectively evaluated the algorithm's marker tracking accuracy for ten prostate cases, analyzing two fractions in each case. Main results. Tracking positional accuracy averaged over all patients was 0.13 ± 0.04 mm (mean ± standard deviation, Euclidean distance) and 0.25 ± 0.09 mm (95th percentile). Computation time was 2.82 ± 0.20 ms/frame averaged over all frames. Significance. Our algorithm successfully and stably tracked irregularly-shaped markers in real time., (© 2024 Institute of Physics and Engineering in Medicine.)

Background: Alcoholic steatohepatitis and nonalcoholic steatohepatitis-related liver cirrhosis (ASH/NASH-LC) are major causes of esophageal varices (EVs). However, the association between high visceral fat and exacerbation of EVs remains unclear. The aim of this study was to clarify the association of visceral fat and recurrence rate of EVs in ASH/NASH-LC and to identify independent predictors associated with recurrence., Methods: We retrospectively evaluated data from 94 patients who underwent endoscopic injection sclerotherapy for EVs with ASH/NASH-LC. Using the receiver operating characteristic curve for the cut-off value of visceral fat index (VFI; 46.4 cm 2 /m 2 ), we classified patients as having a high VFI (n = 53) or low VFI (n = 41). Propensity score matching was used to align for background factors, and the recurrence rate of EVs was compared between the two groups. Predictors associated with esophageal variceal recurrence were identified by multivariate analysis. The recurrence rate in patients with viral LC was also investigated., Results: In the overall analysis, the recurrence rate was significantly higher in the high VFI group than in the low VFI group (P = 0.023). The recurrence rate was also higher in the high VFI group than in the low VFI group after propensity score matching, in which 19 patients were matched in each group (P = 0.048). VFI and Child-Pugh score were independently associated with recurrence. Recurrence rates were comparable between the two groups in viral LC patients., Conclusions: Worsening of variceal recurrence was observed in high visceral fat patients in ASH/NASH-LC but not in viral LC. Furthermore, high visceral fat was an independent predictor associated with variceal recurrence.

Background: The frequency of gallbladder carcinoma is high in pancreaticobiliary maljunction (PBM), and the mechanism of carcinogenesis is not well understood., Methods: The expression of γH2AX, the most sensitive marker for detecting DNA damage, was analyzed using immunohistochemistry in patients with PBM, in which the gallbladder and bile duct were simultaneously resected. Gallbladder and bile ducts were evaluated in non-neoplastic regions in 13 cases of PBM without cancer in the gallbladder and bile ducts., Results: The median frequencies of γH2AX expression in the bile duct and gallbladder within the same case were 5.9% (range 1.7-12.05%) and 9.9% (range 2.8-25%), respectively, and were significantly higher in the gallbladder mucosa (P < 0.0004). γH2AX expression strongly correlated in the bile duct and gallbladder (r = 0.9436, P < 0.0001). PBM caused marked mucosal damage to the gallbladder., Conclusions: Mucosal damage may be involved in carcinogenesis, which may be useful for predicting malignant transformation., Competing Interests: Declaration of Competing Interest I declared on behalf of all authors that all authors have no conflicts of interest to declare., (Copyright © 2023 Elsevier GmbH. All rights reserved.)