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Several donor-specific factors influence the functional recovery and long-term outcomes of liver grafts. This study investigated the association between donor fasting glucose (DFG) and recipient outcomes after living donor liver transplantation (LDLT) in 950 cases at a single center. Patients were divided into two groups: low-DFG (< 85 mg/dL, n = 120) and control (≥ 85 mg/dL, n = 830). The five-year graft survival rate was significantly lower in the low-DFG group (71.5%) compared to the control group (80.0%) (P = 0.02). Multivariable Cox regression analysis showed that low DFG was independently associated with graft loss (hazard ratio 1.72, 95% CI 1.15-2.56, P = 0.008). In propensity score-matched groups, the low-DFG group also had lower survival rates (71% vs. 83.1%, P = 0.004). The presence of additional risk factors, such as low graft-to-recipient weight ratio, older donor age, and longer cold ischemic time, further reduced graft survival in the low-DFG group. A DFG level < 85 mg/dL is associated with higher risk of graft failure after LDLT, especially when combined with other risk factors. Low DFG should be considered a prognostic marker in LDLT planning, with potential to improve patient outcomes as further research clarifies the underlying pathophysiological mechanisms., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Living donor liver transplantation (LDLT) offers timely curative treatment for unresectable hepatocellular carcinoma (HCC). This study aims to validate and compare previous prediction models for HCC outcomes in 488 LDLT recipients., Methods: For 488 patients who underwent LDLT for HCC, pretransplant imaging studies assessed by modified RECSIT criteria, tumor markers such as alpha feto-protein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA II), and explant pathology were recruited. C-index of models for the HCC outcomes was compared, followed by further investigation for the predictive performances of the best model., Results: We found MoRAL (11√PIVKA-II + 2√AFP) demonstrated a higher C-index for HCC recurrence than other models that included radiologically viable tumor number and/or size (MoRAL: 0.709, Milan: 0.537, UCSF: 0.575, Up-to-7: 0.572, French AFP: 0.634, Pre-MORAL: 0.637, HALT-HCC: 0.626, Metroticket2.0: 0.629) and also had the highest C-index for HCC-specific deaths (0.706). Five-year HCC recurrence was well stratified upon dividing the patients into three groups by MoRAL cutoffs (11.9% for MoRAL < 100, 29.6% for MoRAL 100-200, and 48.6% for MoRAL > 200, p < 0.001). However, patients with major vessel invasion or portal vein tumor thrombus showed similarly high HCC recurrence regardless of this grouping (p = 0.612)., Conclusion: The MoRAL, based on tumor markers, showed the best predictive performance for HCC recurrence and HCC-specific death among the validated models, except in cases with major vessel invasion or portal vein tumor thrombus., (© 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Extremely well-differentiated gastric-type adenocarcinoma (EWDGA) is a rare type of gastric cancer composed of deceptively bland-looking malignant cells resembling normal foveolar or pyloric epithelium. The histological features of this tumor have not been recognized by many pathologists, and inter-observer variation studies are lacking. Here, we report seven EWDGAs and inter-observer variation of six preoperative biopsies was evaluated by 11 pathologists in a single institute. Based on the pathological diagnosis of the endoscopic biopsy slides, the average rate of definite malignancy diagnosis was 15.2 %, and the overall diagnostic concordance rate was 34.9 % among 11 pathologists. Microscopically, the surface epithelium was preserved and only a few atypical tumor glands were scattered in most endoscopic biopsies. Structural atypia was minimal, and the tumor glands were barely distinguishable from normal glands. Although nuclear atypia was minimal, enlarged nuclei, relatively large glands with irregular shapes, and abundant cytoplasmic mucin were observed in gastric pinch biopsies. In preoperative biopsies, no cases showed p53 overexpression, and Ki-67 labeling index ranged from 3 % to 35 % and was higher compared to non-neoplastic glands in 3 cases. After gastrectomy, four (57.1 %) patients had advanced gastric cancer and three (42.9 %) had lymph node metastasis. Genomic profiling of the four patients revealed mutations of TP53, BRAF, KRAS, STK11, and MDM2/CCND1 amplification. Immunohistochemistry for p53 was not helpful while Ki-67 may be helpful when staining pattern is distinct from the non-neoplastic mucosa. In conclusion, it is challenging to diagnose EWDGA using biopsy specimens. Recognizing and addressing this rare entity will increase diagnostic accuracy to ensure the early diagnosis of cancer., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Lung cancer is the second most common cancer worldwide and a leading cause of cancer-related deaths. Despite advances in targeted therapy and immunotherapy, the prognosis remains unfavorable, especially in metastatic cases. This study aims to identify molecular changes in non-small cell lung cancer (NSCLC) patients based on their response to treatment. Using tumor and matched immune cell rich peritumoral tissues, we perform a retrospective, comprehensive spatial transcriptomic analysis of a proven malignant NSCLC sample treated with immune checkpoint inhibitor (ICI). In addition to T cells, other immune cell types, such as B cells and macrophages, were also activated in responders to ICI treatment. In particular, B cells and B cell-mediated immunity pathways are consistently found to be activated. Analysis of the histologic subgroup (lung squamous cell carcinoma, LUSC; lung adenocarcinoma, LUAD) of NSCLC also confirms activation of B cell mediated immunity. Analysis of B cell subtypes shows that B cell subtypes were more activated in immune cell-rich tissues near tumor tissue. Furthermore, increased expression of B cell immunity-related genes is associated with better prognosis. These findings provide insight into predicting ICI treatment responses and identifying appropriate candidates for immunotherapy in NSCLC patients., (© 2024. The Author(s).)

Seizures are a frequent neurological consequence following liver transplantation (LT), however, research on their clinical impact and risk factors is lacking. Using a nested case-control design, patients diagnosed with seizures (seizure group) within 1-year post-transplantation were matched to controls who had not experienced seizures until the corresponding time points at a 1:5 ratio to perform survival and risk factor analyses. Seizures developed in 61 of 1,243 patients (4.9%) at median of 11 days after LT. Five-year graft survival was significantly lower in the seizure group than in the controls (50.6% vs. 78.2%, respectively, p < 0.001) and seizure was a significant risk factor for graft loss after adjusting for variables (HR 2.04, 95% CI 1.24-3.33). In multivariable logistic regression, body mass index <23 kg/m 2 , donor age ≥45 years, intraoperative continuous renal replacement therapy and delta sodium level ≥4 mmol/L emerged as independent risk factors for post-LT seizure. Delta sodium level ≥4 mmol/L was associated with seizures, regardless of the severity of preoperative hyponatremia. Identifying and controlling those risk factors are required to prevent post-LT seizures which could result in worse graft outcome., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kang, Koh, Kim, Yim, Choi, Min, Lee, Kim and Joo.)

Background: The benefits of living-donor liver transplantation (LDLT) in patients with a high Model for End-stage Liver Disease (MELD) score (who have high waitlist mortality) are unclear. Regional availability of deceased-donor organs must be considered when evaluating LDLT benefits. The authors aimed to compare the survival benefit of intended-LDLT to awaiting deceased-donor liver transplantation (DDLT) in patients with a MELD score greater than or equal to 30 in a region with severe organ shortage., Materials and Methods: This retrospective review included 649 patients with a MELD score greater than or equal to 30 placed on the liver transplantation waitlist. They were divided into intended-LDLT ( n =205) or waiting-DDLT ( n =444) groups based on living-donor eligibility and compared for patient survival from the time of waitlisting. Post-transplantation outcomes of transplant recipients and living donors were analyzed., Results: Intended-LDLT patients had higher 1-year survival than waiting-DDLT patients (53.7 vs. 28.8%, P <0.001). LDLT was independently associated with lower mortality [hazard ratio (HR), 0.62; 95% CI, 0.48-0.79; P <0.001]. During follow-up, 25 patients were de-listed, 120 underwent LDLT, 170 underwent DDLT, and 334 remained on the waitlist. Among patients undergoing transplantation, the risk of post-transplantation mortality was similar for LDLT and DDLT after adjusting for pretransplantation MELD score (HR, 1.86; 95% CI, 0.73-4.75; P =0.193), despite increased surgical complications after LDLT (33.1 vs. 19.4%, P =0.013). There was no mortality among living-donors, but 4.2% experienced complications of grade 3 or higher., Conclusions: Compared to awaiting DDLT, LDLT offers survival benefits for patients with a MELD score greater than or equal to 30, while maintaining acceptable donor outcomes. LDLT is a feasible treatment for patients with a MELD score greater than or equal to 30 in regions with severe organ shortages., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Comprehensive molecular subtyping of diffuse large B-cell lymphoma (DLBCL) through genetic profiling has broadened our understanding of DLBCL biology. In this study, we investigated whether DLBCL, not otherwise specified (NOS) shows differences in mutational patterns depending on the primary organ., Patients and Methods: Panel-based next-generation sequencing was performed on 345 DLBCL from various primary organs, and patterns of mutations according to primary organs were analyzed., Results: DLBCL showed a characteristic mutational signature in several primary organs. Among them, the mutational pattern of DLBCL in the breast and ileocecal area was particularly different from that of other DLBCL NOS. In breast DLBCL, MYD88 L265P (57.1%), CD79B mutation (42.9%), and CDKN2A/B loss (71.4%) were found at high frequencies, which were similar to the mutation patterns of DLBCL of immune-privileged sites compared with DLBCL NOS. DLBCL in the ileocecal area showed a characteristic mutation pattern with the most frequent TP53 mutation (52.6%) and 18q21 gain (42.1%). This was also different from the mutational pattern observed in the stomach or other intestines. In discriminant analysis, DLBCL of the breast and ileocecal area tended to form separate genetic constellations from other DLBCL NOS., Conclusion: DLBCL NOS has a characteristic mutational profile that depends on the primary organ. In particular, the mutational signature of DLBCL in the breast and ileocecal area was heterogeneous compared with that of other DLBCL NOS. Further research is needed to determine whether primary DLBCL in the breast and ileocecal area can be classified as an independent subtype., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Purpose: Albumin-bilirubin (ALBI) score is a well-known prognostic factor for various diseases, including colorectal cancer (CRC). However, little is known about the significance of postoperative ALBI score changes in patients with CRC., Materials and Methods: A total of 723 patients who underwent surgery were enrolled. Preoperative ALBI (ALBI-pre) and postoperative ALBI (ALBI-post) scores were divided into low and high score groups. ALBI-trend was defined as a combination of four groups comprising the low and high ALBI-pre and ALBI-post score groups. Kaplan-Meier survival curves were used to compare the overall survival (OS) between the different ALBI groups. The Cox proportional hazards model was used to examine the independent relevant factors of OS. Stratification performance was compared between the different ALBI groupings using Harrell's concordance index (C-index)., Results: ALBI-pre, ALBI-post, and ALBI-trend score groups were significant prognostic factors of OS in the univariable analysis. However, multivariable analysis showed that ALBI-trend was an independent prognostic factor while ALBI-pre and ALBI-post were not. The C-index of ALBI-trend (0.622; 95% confidence interval [CI], 0.587 to 0.655) was higher than that of ALBI-pre (0.589; 95% CI, 0.557 to 0.621; bootstrap mean difference, 0.033; 95% CI, 0.013 to 0.057) and ALBI-post (0.575; 95% CI, 0.545 to 0.605; bootstrap mean difference, 0.047; 95% CI, 0.024 to 0.074)., Conclusion: Combining ALBI-pre and ALBI-post scores is an independent prognostic factor of OS and shows superior predictive power compared to ALBI-pre or ALBI-post alone in patients with CRC.

Data on genetic and immunophenotypical characteristics of uterine mesonephric-like adenocarcinoma (MLA) remain limited. Therefore, we aimed to investigate the clinicopathological, immunohistochemical, and molecular features of uterine MLA. We performed targeted sequencing, array comparative genomic hybridization, and immunostaining in 17, 13, and 17 uterine MLA cases, respectively. Nine patients developed lung metastases. Eleven patients experienced disease recurrences. The most frequently mutated gene was Kirsten rat sarcoma viral oncogene homolog ( KRAS ; 13/17). Both the primary and matched metastatic tumors harbored identical KRAS (3/4) and phosphatase and tensin homolog deleted on chromosome 10 (1/4) mutations, and did not harbor any additional mutations. A total of 2 of the 17 cases harbored tumor protein 53 ( TP53 ) frameshift insertion and deletion, respectively. Chromosomal gains were detected in 1q (13/13), 10 (13/13), 20 (10/13), 2 (9/13), and 12 (6/13). Programmed cell death-ligand 1 overexpression or mismatch repair deficiency was not observed in any of the cases. Initial serosal extension and lung metastasis independently predicted recurrence-free survival with hazard ratios of 6.30 and 7.31, respectively. Our observations consolidated the clinicopathological and molecular characteristics of uterine MLA. Both clinicians and pathologists should consider these features to make an accurate diagnosis of uterine MLA and to ensure appropriate therapeutic management of this rare entity.

Background/aim: Alteration of F-box and leucine-rich repeat protein 5 (FBXL5), an iron-sensing ubiquitin ligase, might be related with carcinogenesis of hepatocellular carcinoma (HCC), by disturbing cellular iron homeostasis. However, the clinical implications of FBXL5 expression using patient samples need to be elucidated., Patients and Methods: We collected HCC tissue samples from two institutes: Samsung Medical Center (n=259) and Hallym University Sacred Heart Hospital (n=115) and evaluated FBXL5 expression using immunohistochemistry. Using cut-off values determined by X-tile software, association between FBXL5 expression and several clinicopathological parameters was investigated. For external validation, the Cancer Genome Atlas (TCGA) cohort was used., Results: The best cutoff value for FBXL5 IHC expression associated with recurrence-free survival (RFS) was 5%. Low FBXL5 expression was found in 18.7% of the total 374 HCCs and was associated with non-viral etiology (p=0.019). Low FBXL5 expression was related with inferior disease-specific survival (DSS, p=0.002) and RFS (p=0.001) and also was an independent prognostic factor for DSS and RFS. In addition, cases with low FBLX5 mRNA levels showed inferior DSS and RFS (p<0.001 and p=0.002, respectively) compared to high FBLX5 mRNA levels in the TCGA cohort., Conclusion: Down-regulation of FBXL5 expression in HCCs might be associated with poor prognosis. FBXL5 might be a prognostic biomarker of HCCs and a potential therapeutic target in conjunction with iron homeostasis., (Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Because different types of thyroid malignancies have distinct embryological origins, coexisting tumors are rarely observed. We describe a coexisting papillary thyroid carcinoma (PTC) and medullary thyroid carcinoma (MTC) first suspected by fine-needle aspiration cytology (FNAC). A 57-year-old female presented with an irregular mass in the right thyroid lobe. The cytopathologic findings of fine-needle aspiration showed two components: a papillary-like arrangement consisting of cells with pale enlarged nuclei indicative of PTC and loose clusters comprised of oval cells with granular chromatin indicative of MTC. The diagnosis of a coexisting PTC and MTC was initially confirmed by calcitonin immunocytochemistry and later after total thyroidectomy. Although some surgical case reports of PTC and MTC coexisting in either the same or different lobes have been documented, a case suspected by FNAC before the surgery has rarely been reported. Because appropriate treatment and prognosis of PTC and MTC are different, cytopathologists should be aware of this rare entity.

Detection of oncogenic fusion genes in cancers, particularly in the diagnosis of uncertain tumors, is crucial for determining effective therapeutic strategies. Although novel fusion genes have been discovered through sequencing, verifying their oncogenic potential remain difficult. Therefore, we evaluated the utility of targeted RNA sequencing in 165 tumor samples by identifying known and unknown fusions. Additionally, by applying additional criteria, we discovered eight novel fusion genes that are expected to process oncogenicity. Among the novel fusion genes, RAF1 fusion genes were detected in two cases. PTPRG-RAF1 fusion led to an increase in cell growth; while dabrafenib, a BRAF inhibitor, reduced the growth of cells expressing RAF1. This study demonstrated the utility of RNA panel sequencing as a theragnostic tool and established criteria for identifying oncogenic fusion genes during post-sequencing analysis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 An, Koh, Chang, Choi, Song, Lee and Choi.)

Background: The albumin-bilirubin (ALBI) grade is a useful prognostic and predictive marker for patients with liver disease. Its clinical significance has been limited to patients with colorectal cancer (CRC). Furthermore, the association between the ALBI grade and skeletal muscle-related indices is unclear., Methods: This study enrolled 1015 patients who underwent computed tomography (CT) scans within 31 days before surgery. The prognostic value of the ALBI grade in predicting overall survival (OS) was assessed using the Cox proportional hazards model. The correlation between the ALBI grade and the skeletal muscle index or radiodensity (myosteatosis) was evaluated. The predictive accuracy of ALBI alone and in combination with myosteatosis was compared using Harrell's concordance index (C-index)., Results: The significant prognostic factors for OS identified in the multivariable analysis were the ALBI group (low vs high: hazard ratio [HR], 1.566; 95 % confidence interval [CI], 1.174-2.089; p = 0.002) and myosteatosis (low vs. high: HR, 0.648; 95 % CI, 0.486-0.865; p = 0.003). The rate of low-grade myosteatosis increased as the ALBI grade increased. The C-index of combined ALBI and myosteatosis (0.650; 95 % CI, 0.618-0.683) was superior to that of ALBI alone (0.603; 95 % CI, 0.575-0.631; bootstrap incremental area under the curve [iAUC] mean difference, 0.047; 95 % CI, 0.012-0.070) and myosteatosis alone (0.608; 95 % CI, 0.577-0.640; bootstrap iAUC mean difference, 0.042; 95 % CI, 0.023-0.064)., Conclusion: The ALBI grade is significantly associated with myosteatosis. The ALBI grade is a significant prognostic factor, and the combination of ALBI and myosteatosis show an additive value in discriminating survival of patients with CRC., (© 2022. Society of Surgical Oncology.)

Background/aim: Transient receptor potential vanilloid 6 (TRPV6), an endothelial Ca 2+ -selective entry channel, is expressed in various cancer types, and a selective TRPV6 inhibitor is currently being investigated in a clinical trial. However, TRPV6 expression in hepatocellular carcinoma (HCC) has not been reported., Materials and Methods: We evaluated TRPV6 expression in 219 cases of HCC and analyzed its association with clinicopathological parameters and prognostic significance. TRPV6 mRNA expression was compared between HCC and non-tumor liver tissues using various public datasets, and its prognostic effect was examined in The Cancer Genome Atlas (TCGA) cohort., Results: Low TRPV6 expression was found in 37.4% of patients, which was significantly associated with adverse histologic features, and patients with low TRPV6 expression had shorter recurrence-free and disease-free survival. TRPV6 mRNA expression was consistently lower in HCC compared to non-tumor liver samples in public datasets, at the whole tissue level as well as single-cell level. Patients with low TRPV6 expression in the TCGA cohort had shorter progression-free survival., Conclusion: TRPV6 expression is down-regulated in HCCs and associated with a poor prognosis. TRPV6 may be a prognostic biomarker in HCC., (Copyright © 2022, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Mesonephric-like adenocarcinoma (MLA) arising in the ovary is a rare malignant tumor of the female genital tract. Although the clinicopathological and molecular characteristics of uterine MLA have been accumulated, those of ovarian MLA have not been firmly clarified. In this study, we investigated the clinicopathological, immunohistochemical, and genetic features of five ovarian MLAs. A review of electronic medical records and pathology slides, immunostaining, and targeted sequencing was performed. On imaging, ovarian MLA presented as either a mixed solid and cystic mass or a purely solid mass. One, three, and one patient were diagnosed as having FIGO stage IA, IC, and II MLA, respectively. Four patients with stage IC-II tumor underwent post-operative adjuvant chemotherapy. Three of the four patients whose follow-up information was available did not experience recurrence. In contrast, the remaining patient with stage IA tumor who did not receive any adjuvant treatment developed multiple metastatic recurrences at post-operative 13 months. Histologically, ovarian MLAs characteristically displayed architectural diversity, compactly aggregated small tubules, and eosinophilic intraluminal secretions. Four tumors were found to be associated with endometriotic cysts. Two cases showed some areas of high-grade nuclear atypia, brisk mitotic activity, and necrosis. Immunohistochemically, all cases showed positive immunoreactivities for at least three of the four examined mesonephric markers (GATA3, PAX2, TTF1, and CD10), lack of WT1 expression, non-diffuse p16 immunoreactivity, and wild-type p53 immunostaining pattern. Targeted sequencing analysis revealed that all four examined cases harbored pathogenic KRAS mutations: p.G12V (2/4); p.G12D (1/4); and p.G12C (1/4). In addition, we reviewed the previous literature reporting 60 cases of ovarian MLA. Our findings corroborate those of the previous data regarding the clinical presentation, histological features, immunophenotypes, and molecular alterations. Our observations should encourage pathologists to recognize and accurately diagnose this rare but distinct entity.

Background: ZMYND8 (Zinc finger MYND (Myeloid, Nervy and DEAF-1)-type containing 8) has been known to play an important role in tumor regulation in various types of cancer. However, the results of ZMYND8 expression and their clinical significance in hepatocellular carcinoma (HCC) have not yet been published. In the present study, we investigate the expression of ZMYND8 protein and mRNA in HCC and elucidate its prognostic significance., Methods: ZMYND8 protein and mRNA expression in 283 and 234 HCCs were investigated using immunohistochemistry and microarray gene expression profiling data. The relationships between ZMYND8 expression with clinicopathologic features and prognosis of HCC patients were evaluated. Furthermore, we performed the invasion, migration, apoptosis, soft agar formation assay and sphere formation assay in HCC cell lines, and evaluated tumorigenicity in a nude mouse model, after ZMYND8 knockdown., Results: Overexpression of ZMYND8 protein and mRNA was observed in 20.5% and 26.9% of HCC cases, respectively. High ZMYND8 expression showed significant correlations with microvascular invasion, high Edmondson grade, advanced American Joint Committee on Cancer, and increased alpha-fetoprotein level. ZMYND8 mRNA overexpression was an independent prognostic factor for predicting early recurrence as well as short recurrence-free survival (RFS). Downregulation of ZMYND8 reduced migration and invasion of HCC cells, and promoted apoptosis of HCC cells in an in vitro model. In a xenograft nude mouse model, knockdown of ZMYND8 significantly reduced tumor growth., Conclusion: ZMYND8 mRNA overexpression could be a prognostic marker of shorter RFS in HCC patients after curative resection. ZMYND8 might play an important role in the proliferation and progression of HCC and could be a promising candidate for targeted therapy., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background/aim: The diagnosis of gastric-type endocervical adenocarcinoma (GEA) is challenging because its differential diagnosis includes not only gynecological tumors, but also extragenital tumors., Patients and Methods: We reviewed the electronic medical records and all available slides to investigate the clinicopathological characteristics of eight misdiagnosed GEA cases., Results: Three tumors were initially misdiagnosed as endometrial carcinoma. They displayed extensive endomyometrial involvement and complex glandular architecture, but no severe nuclear pleomorphism. Another three tumors were misclassified as usual-type endocervical adenocarcinoma because of mucin-poor, pseudoendometrioid glands, apical mitotic figures, and karyorrhectic debris. The two remaining tumors presenting as adnexal masses mimicked primary ovarian mucinous tumor and metastatic cholangiocarcinoma., Conclusion: The varying pathological characteristics of GEA reflect the variability in clinical manifestations and its diagnostic difficulties. It is challenging to make an accurate diagnosis based solely on histological features. When suspecting GEA, clinicians should consider more comprehensively the clinicopathological context, along with immunostaining results., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

We herein present a case of uterine cervical invasive micropapillary carcinoma (IMPC) in a 35-year-old woman. She had neither specific symptoms nor any previous gynecological history. A cervical punch biopsy revealed a high-grade squamous intraepithelial lesion and concurrent intestinal-type mucinous carcinoma. Based on the preoperative diagnosis of endocervical adenocarcinoma, she underwent radical hysterectomy with bilateral salpingo-oophorectomy and bilateral pelvic lymph node dissection. Grossly, there was an ovoid, slightly elevated mass with surface nodularity in the lower endocervix, measuring 10 × 8 mm. Histologically, the tumor consisted predominantly of tufts of tumor cells arranged in micropapillary structures devoid of fibrovascular cores and surrounded by clear, empty, lacunar spaces between tumor cell nests and stroma. The IMPC component comprised 90% of the entire tumor volume. The greatest dimension and stromal invasion depth of the IMPC were 8 and 3 mm, respectively (FIGO stage IA2). Immunostaining revealed that mucin 1 (MUC1) surrounded each micropapillary structure, indicating the reverse epithelial polarity of the glandular cells. MUC1 was localized predominantly in the stroma-facing surface of the cell clusters, accentuating the outlines of the micropapillary structures by forming a distinct, characteristic band on this surface. In addition, targeted sequencing analysis of the IMPC revealed a missense PIK3CA mutation (c.1633G>A). In summary, we present the clinicopathological characteristics of cervical IMPC. We demonstrate for the first time that IMPC of the uterine cervix harbors a pathogenic missense mutation in PIK3CA . Further investigations using larger cohorts of patients are necessary to confirm these findings., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2020 by S. Karger AG, Basel.)

Background/aim: To investigate the clinicopathological characteristics of high-grade squamous intraepithelial lesions (HSILs) and squamous cell carcinomas (SCCs) involving endocervical polyps (ECPs)., Patients and Methods: We collected the endocervical polypectomy cases and performed pathological examination and cytohistological correlation., Results: During a period of 12 years, 21 (1.1%) HSILs and two (0.1%) SCCs involving ECPs were identified in 1,905 cases. Twelve (63.1%) of the 19 cases were cytohistologically concordant. In five HSILs and one SCC with polypectomy margin involvement, residual HSIL was identified in conization or hysterectomy specimens. Furthermore, in two HSIL patients and one SCC patient with negative polypectomy margins, residual HSILs were found in the conization specimens., Conclusion: The prevalence of HSIL and SCC involving ECP in our cohort was similar to the rates found in previous studies. The presence of residual HSIL in nonpolypoid cervical tissue regardless of the polypectomy margin involvement suggests that conization or hysterectomy is needed for diagnostic or treatment purposes., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: The Paris System (TPS) has recently been proposed as a method to standardize urinary cytology reporting. In this study, we evaluated the impact of implementing TPS compared to the traditional reporting system., Patients and Methods: In total, 299 urine samples were reclassified according to TPS. We examined correlations between cytological and histological diagnoses, and calculated probabilities for detecting high-grade urothelial carcinoma (HGUC)., Results: TPS resulted in a decrease in the proportion of cases diagnosed as atypical urothelial cell (AUC) (43% to 31%). Among the AUC cases, the proportion of histologically confirmed HGUC cases rose (75% to 80%), as did the proportion of low-grade urothelial neoplasms (57% to 71%). All probabilities for detecting HGUC significantly increased using TPS., Conclusion: TPS improved the diagnostic yield of urinary cytology. The implementation of TPS is expected to be a major step towards standardizing urinary cytology reporting and providing clear information to clinicians., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Gastric carcinoma (GC) is the second most common cause of cancer-related deaths worldwide. During operations, nodular lesions of the peritoneum are often sent for frozen section (FS). For pathologists, FS of the peritoneum is challenging due to sparse and discohesive tumor cells in a fibrotic background., Methods: To explore diagnostic accuracy and diagnostic pitfalls of FS in this setting, we retrospectively collected 252 peritoneal biopsies in cases with GC from January 2006 to May 2017 and compared corresponding permanent sections and patient prognosis. After review, 6 cases (2.4%) were discrepant: positive conversion was identified in 5 cases due to scarce tumor cells associated with severe fibrosis and inflammation; negative conversion was identified in one case due to papillary mesothelial cell proliferation masquerading as carcinoma., Results: Two hundred cases were finally confirmed as positive for tumor cells. Of these, 185 (92.5%) patients died of GC, with survival times ranging from 7 to 3574 (mean 415) days after operation. Fifty-two (20.6%) cases were negative for tumor, and pathologic findings included chronic inflammation with fibrosis (N = 25: associated with previous operation, 10; idiopathic, 15) and papillary mesothelial cell proliferation (N = 9). All 5 patients with frozen diagnosis converted to positive results died of GC during follow up. A total of 19 patients with peritoneal nodules diagnosed as benign on FS died with GC (79.0%), and their survival times ranged from 87 to 3649 (mean 833) days., Conclusions: Peritoneal biopsies in patients with GC were mostly carcinoma, followed by chronic inflammation with fibrosis and papillary mesothelial cell proliferation. Deeper sections or intradepartmental consultations were helpful to reduce false negative diagnosis on FS., (Copyright © 2018 Elsevier GmbH. All rights reserved.)

Background: Pulmonary nodular lymphoid hyperplasia (PNLH) is a non-neoplastic pulmonary lymphoid disorder that can be mistaken for malignancy on radiography. Herein, we present nine cases of PNLH, emphasizing clinicoradiological findings and histological features., Methods: We analyzed radiological and clinicopathological features from the electronic medical records of nine patients (eight females and one male) diagnosed with PNLH. IgG and IgG4 immunohistochemical staining was performed in three patients., Results: Two of the nine patients had experienced tuberculosis 40 and 30 years prior, respectively. Interestingly, none were current smokers, although two were ex-smokers. Three patients complaining of persistent cough underwent computed tomography of the chest. PNLH was incidentally discovered in five patients during examination for other reasons. The remaining patient was diagnosed with the disease following treatment for pneumonia. Imaging studies revealed consolidation or a mass-like lesion in eight patients. First impressions included invasive adenocarcinoma and mucosal-associated lymphoid tissue‒type lymphoma. Aspergillosis was suspected in the remaining patient based on radiological images. Resection was performed in all patients. Microscopically, the lesions consisted of nodular proliferation of reactive germinal centers accompanied by infiltration of neutrophils and macrophages in various degrees and surrounding fibrosis. Ultimately, all nine patients were diagnosed with PNLH and showed no evidence of recurrence on follow-up., Conclusions: PNLH is an uncommon but distinct entity with a benign nature, and understanding the radiological and clinicopathological characteristics of PNLH is important.

Background: Survival with good neurological function post out-of-hospital cardiac arrest (OHCA), defined as cerebral performance category (CPC) 1-2, ranges from 1.6% to 3% in Asia. We aim to study the influence of comorbidities and peri-OHCA event factors on neurological recovery and develop a model that can help clinicians predict neurological function among patients with post-OHCA admitted to the hospital., Methods: This was a retrospective cohort study. All patients admitted post-OHCA from 1 January 2011 to 31 December 2015 to a tertiary centre were identified through the hospital OHCA registry. Patients who survived till hospital admission were included. Logistic regression was used to identify patient and peri-arrest factors that were significantly associated with survival with CPC 1-2. The significant factors for survival with CPC 1-2 were then put into a multivariable model and the discriminative ability was tested using the receiver operator characteristic (ROC) curve. Calibration and internal validation of the model were also performed. External validation in a small prospective cohort was also performed., Results: In our derivation cohort of 129 patients, 30.23% survived with CPC 1-2. Significant factors associated with survival with good neurological outcomes were age-adjusted Charlson Comorbidity Index ≤5, time to first return of spontaneous circulation ≤40 min, the presence of immediate bystander cardiopulmonary resuscitation and shockable rhythms. We also developed a nomogram which showed good internal (ROC curve 0.84; 95% CI 0.77 to 0.91) and external validation (ROC curve 0.90; 95% CI 0.81 to 1.00)., Competing Interests: Competing interests: None declared.

There is a growing body of evidence which suggests that macular pigment (MP), which is entirely of dietary origin, protects against age-related maculopathy. We evaluated the effect of a daily 20 mg lutein ester (equivalent of 10 mg/day free lutein) supplement in patients with early age-related maculopathy (ARM), in terms of macular pigment optical density (MPOD) and plasma concentrations of lutein. MPOD was measured using a flicker photometric technique in seven ARM sufferers and six age-matched controls over a period of supplementation which lasted 18-20 weeks. Plasma lutein increased from a mean (SD) baseline concentration of 182 (127)ng ml(-1) to a peak of 1077 (165)ng ml(-1) in ARM patients, and from 152 (57) to 1110 (605)ng ml(-1) in control subjects. Mean MPOD had increased significantly from baseline of 0.24 to a peak of 0.31 in ARM sufferers. This mean increment of 0.07 was the same for the age-matched controls (baseline: 0.20; peak: 0.27). The augmentation of MP, and plasma concentrations of lutein, following supplementation in subjects with ARM provides the first evidence the disease is not associated with intestinal malabsorption of the relevant macular carotenoids, and that a diseased macula can accumulate and stabilise lutein and/or zeaxanthin. Furthermore, these results suggest that the beneficial effects of lutein supplementation, if any, may be extended to subjects with established ARM.

Background: Striae and folds are observed with a slitlamp biomicroscope in the cornea following overnight contact lens wear. These phenomena are poorly understood. The aim of this study is to employ confocal microscopy to observe and document these and other morphological changes in the human cornea following overnight contact lens wear., Methods: Slitlamp biomicroscopy, slit-scanning confocal microscopy and ultrasonic pachometry were performed on both eyes of 13 subjects (3M, 10F, age 24 +/- 3 years) before and after eight hours overnight wear of a -3.00 D Bausch & Lomb one day disposable soft contact lens (Dk/t = 15.1 x 10(-9) [cm/sec] x [ml O2/ml x mmHg]) in one eye; the other non-lens-wearing eye acted as a control., Results: Following sleep, both corneas were swollen (lens-wearing eye 11.8 +/- 3.8 per cent; control eye 2.1 +/- 1.9 per cent) and the stroma of both corneas displayed an apparent reduction in keratocyte density (lens-wearing eye 21 per cent; control eye 10 per cent). Folds were observed with the slitlamp biomicroscope and long, straight, dark, orthogonal lines were observed with the confocal microscope, in the posterior stroma of the oedematous lens-wearing eyes. Such features were not observed in the control eyes. The keratocytes appeared less distinct with greater levels of corneal oedema., Conclusion: The apparent loss of keratocytes following overnight lens wear is an optical artefact that can be explained in terms of corneal oedema causing volumetric tissue expansion and a loss of optical clarity, which hampers keratocyte detection. These findings place the onus on researchers postulating a loss of stromal keratocytes following clinical interventions, such as contact lens wear, to account for the effects of oedema.

A compact device to derive the optical density of human macular pigment (MP) using heterochromatic flicker photometry is described. The validity of the system is assessed by measuring the optical density spectra of MP in 12 healthy subjects and comparing this with well-established previously published values. The mean spectral absorbance characteristics of MP across subjects corresponds well with accepted values. As reported in other studies, our measurements show a wide variation of MP optical densities between individuals. In our technique within-subject variability is low; standard deviations are between 0.025 and 0.15 in most cases. The overall optical density of MP ranged from 0.08 to 0.84 with a mean of 0.496 and standard deviation of 0.257 at 460 nm. The stimulus size was 0.95 degrees. The unique feature of the technique is that it allows free viewing (not Maxwellian View) of the stimulus, it can be conducted easily and quickly and does not need frequent re-calibration.