Comparative Immunohistochemical Analysis of Clinicopathological Subgroups in Hepatocellular Carcinomas from Japan and Indonesia.

Background: Standardized pathological evaluation based on immunohistochemical (IHC) analysis could improve hepatocellular carcinoma (HCC) diagnoses worldwide. We evaluated differences in clinicopathological subgroups in HCCs from two academic institutions in Tokyo-Japan, and Jakarta-Indonesia. Methods: Clinicopathological parameters and molecular expression patterns were evaluated in 35 HCCs from Indonesia and 41 HCCs from Japan. IHC analysis of biliary/stem cell (B/S) markers (cytokeratin 19, sal-like protein 4, epithelial cell adhesion molecule) and Wnt/ß-catenin (W/B) signaling-related molecules (ß-catenin, glutamine synthetase) could determine the IHC-based subgroups. For immuno-subtypes categorization, CD3/CD79α double immunohistochemistry was done to evaluate the infiltration of T and B cells. CD34 staining allowed identification of vessels that encapsulated tumor clusters (VETC). Results: Indonesian HCC patients were mostly <60 years old (66%) with a hepatitis B virus (HBV) background (82%), in contrast to Japanese HCC patients (8% and 19%, respectively, both P < 0.001). In comparison with Japanese, Indonesian cases more frequently had >5 cm tumor size (74% vs 23%, P = 0.001), poor differentiation (40% vs 24%), portal vein invasion (80% vs 61%), and α-fetoprotein levels >500 ng/ml (45% vs 13%, P = 0.005). No significant differences were found in the proportions of B/S, W/B, and -/- subgroups from both countries. No immune-high tumors were observed among Indonesian cases, and immune-low tumors (66%) were more common than in Japanese cases (54%). VETC-positive tumors in Indonesia were significantly more common (29%), and most were in the HBV (90%) and -/- subgroups (90%), whereas Japanese VETC cases (10%, P = 0.030) were nonviral (100%) and W/B subgroups (75%). Conclusion: IHC-based analysis more precisely reflected the clinicopathological differences of HCCs in Japan and Indonesia. These findings provide new insights into standardization attempts and HCC heterogeneity among countries.

Estimated projection of oral squamous cell carcinoma annual incidence from twenty years registry data: a retrospective cross-sectional study in Indonesia.

Background: The incidence of oral squamous cell carcinoma (OSCC) has not been well documented in Indonesia. Thus, we aimed to analyze trends and clinicopathological profiles of OSCC cases in Indonesia, focusing on differences between age and sex groups. Methods: A cross-sectional study was conducted in Indonesia's main referral hospital, analyzing 1,093 registered OSCC cases from 2001 to 2020. Trend analysis was performed using Joinpoint regression analysis to determine the annual percentage change (APC) for overall cases and each case group based on age, sex, and anatomical subsites. APC significance was assessed using a Monte Carlo permutation test. The projection of case numbers for the following 5 years (2021-2025) was estimated using linear/non-linear regression analysis and presented as a mathematical function. The significance of the trend slope was measured using an ANOVA test. Demographic and clinicopathological characteristics of OSCC were analyzed according to age and sex, and their comparative analysis was assessed using Chi-square and its alternatives. Results: The incidence of OSCC in female patients and in the tongue and buccal mucosa showed a positive trend (APC 2.06%; 3.48%; 8.62%, respectively). Moreover, the incidence of OSCC overall, and in women with OSCC, is projected to increase significantly in the next 5 years following the quadratic model. The mean age of patients was 51.09 ± 14.36 years, with male patients being younger than female patients. The male-to-female ratio was 1.15, and 36.5% of these patients were categorized as young (≤45 years old). The tongue was the predominantly affected site. Prominent pathologic characteristics included well-differentiation, keratinization, and grade I of Bryne's (1992) cellular differentiation stage. Most patients presented with advanced staging, lymphovascular invasion, and uninvaded margins. Tumor sites and staging varied according to age, while age and tumor sites differed between sexes. Conclusion: The rising incidence trends of OSCC among Indonesian patients, both in the past and projected future, are concerning and warrant attention. Further research into risk factors should be conducted as preventive measures.

p53 expression is associated with tumor stage, grade and subtype in patients with hepatocellular carcinoma.

The present study aimed to determine the expression levels of p53 in patients with hepatocellular carcinoma (HCC) and to evaluate its association with several HCC-related prognostic factors and in particular, with tumor stage, grade and subtype. Therefore, a cross-sectional study, involving 41 patients with HCC, who underwent surgical resection between January, 2013 and December, 2020 was conducted. To assess the expression levels of p53 in all patients with HCC, immunohistochemical staining was performed. In addition, the association between p53 expression and the clinicopathological characteristics of patients with HCC, including prognostic factors, was evaluated by applying the appropriate statistical analysis methods. The results revealed that among the 41 patients enrolled, 35 patients (85.4%) were positive for p53 expression. A higher percentage of positive p53 expression was observed in male patients >60 years old, with single HCC nodules >5 cm in diameter and vascular invasion, compared with their counterparts. A positive p53 expression was associated with well- and poorly differentiated HCC, but not with tumor stage and subtype. No differences in p53 expression were observed across different tumor stages and subtypes. Additionally, patients with moderately and poorly differentiated HCC exhibited significantly higher p53 expression levels compared with those suffering from well-differentiated HCC. Overall, the results demonstrated that the rate of p53 immuno-positive cells was increased in patients with HCC. In addition, p53 expression was associated with well- and poorly differentiated HCC, thus suggesting its association with a poorer prognosis.

Clinical implications of Cytokeratin 19 expression in patients with oral squamous cell carcinoma.

Objective: This study was done to quantify the prevalence of high cytokeratin (CK) 19 expression in Indonesian oral squamous cell carcinoma (OSCC) patients and explore the prognostic role of CK19 in OSCC. Methods: Clinical data and samples from 61 patients diagnosed with OSCC at a tertiary national referral hospital in Jakarta, Indonesia were analyzed in this retrospective cohort study. Immunohistochemical staining of CK19 was performed on all patients and its expression was scored using the H system. All patients were followed up for a minimum of 36 months after diagnosis. Comparative and survival analyses were performed. Results: Twenty six point two percent of Indonesian OSCC patients had high CK19 expression. There were no differences in clinicopathological characteristics between patients with low and high CK19 expression. The 3-year overall survival (OS) of our cohort was 11.5%. Patients with high CK19 expression had lower 3-year OS compared to patients with low CK19 expression, even if the difference in OS was not statistically significant. Keratinization was an independent prognostic factor for survival in multivariate regression analysis. Conclusions: Data obtained here indicate a possible prognostic role of CK19 in OSCC. This prognostic role should be confirmed in larger series.

Clinicopathological characteristics predicting advanced stage and surgical margin invasion of oral squamous cell carcinoma: A single-center study on 10 years of cancer registry data.

The incidence profile of oral squamous cell carcinoma (OSCC) has not previously been comprehensively reported in Indonesia. The present study aimed to identify clinicopathological characteristics of patients with OSCC according to sex and age, to analyze histological differentiation patterns specific to tumor subsites, to highlight the role of lymphovascular invasion (LVI) in metastasis, and to develop a model to predict advanced stage and margin invasion. A retrospective cross-sectional study was performed using 581 medical records and pathological specimens from cancer registry data in the Dr Cipto Mangunkusumo Hospital (Jakarta, Indonesia), between January 2011 and December 2020. Clinicopathological characteristics were analyzed using parametric and non-parametric tests. Multivariate logistic regression analyses were performed for eligible parameters, identified using bivariate analysis, to predict advanced stage and margin invasion. Calibration of the prediction model was evaluated using the Hosmer-Lemeshow test, its discrimination value assessed using the receiver operating characteristic and area under the receiver operating characteristic curve (AUC). Sex-specific patterns in tumor subsites and differences in clinical staging according to age were demonstrated in the patients with OSCC. The proportion of well-differentiated cases was significantly higher in most tumor subsites, except in the buccal mucosa (more moderately differentiated cases) and floor of the mouth (well and moderately differentiated cases being equal). LVI was significantly associated with nodal metastasis but not distant metastasis. Multivariate analysis demonstrated that age ≤45 years [odds ratio (OR), 2.26] and LVI (OR, 8.42) predicted patients having advanced-stage OSCC among general populations (AUC, 0.773); however, LVI (OR, 8.28) was the sole predictor of advanced stage amongst young patients (AUC, 0.737). Margin invasion was predicted solely by tumor subsite, including mouth not otherwise specified (OR, 3.04) and palate (OR, 6.13), in the general population (AUC, 0.711). Furthermore, margin invasion was predicted by the palate subsite (OR, 38.77) and LVI (OR, 11.61) in young patients (AUC, 0.762). Investigating young patients thoroughly when finding SCC in the mouth and palate, and assessing LVI, especially among young patients, is critical to prevent advanced staging and margin invasion.

Fulminant necrotizing amoebic colitis presenting as acute appendicitis: a case report and comprehensive literature review.

Intestinal amoebiasis is a parasitic infection caused by Entamoeba histolytica. It is commonly found in developing countries with poor hygiene. A rare, life-threatening complication of amoebiasis is fulminant necrotizing amoebic colitis (FulNAC). We report a 59-year-old male with acute lower right abdominal pain. Before coming to our institution, he was diagnosed with acute appendicitis. Extensive necrosis near the caecum involving the appendix and colon was observed intraoperatively. The patient underwent a right hemicolectomy, followed by an ileostomy and colostomy. Histopathologic examination confirmed the diagnosis of FulNAC. After the surgery, the patient was transferred to the high care unit and treated with metronidazole after histopathologic findings confirmed the etiology. The patient showed excellent response to the antibiotic prescribed, and the symptoms subsided. He was discharged from the hospital on day nine. Additionally, we reviewed fifty-one existing case reports on invasive intestinal amoebiasis worldwide, confirmed by histopathological examination following their preoperative diagnosis, surgery, pharmacology treatment, and outcomes. The learning point of this case is that intestinal amoebiasis should be considered a differential diagnosis for patients around fifty years old with bowel symptoms and travel history or living in tight quarters. Blood tests, radiological examinations, and serological evaluations are valuable diagnostic modalities. Metronidazole should be given as early as possible, and health promotion is recommended to prevent this disease in the population.

Clinicopathological Profile of Thyroid Carcinoma in Young Patients: An Indonesian Single-Center Study.

INTRODUCTION: Thyroid cancer is the third most common cancer that occurs in children and adolescents. Papillary thyroid carcinoma (PTC) is the most common type of thyroid malignancy. Although the mortality rate of thyroid malignancy in children is usually low, the disease recurrence is higher in children with more severe clinical presentation than in adults. This study aimed to determine the demographic and clinicopathological characteristics and outcome of pediatric and adolescent patients with thyroid malignancy in Indonesia. METHODS: The retrospective study included all patients diagnosed with thyroid carcinoma aged <20 years, from January 1, 2015, to December 31, 2019. Twenty-nine subjects fulfilled the inclusion and exclusion criteria. We retrieved baseline characteristics, pathology features, TSH and fT4 status, radioactive iodine therapy data, and patients' outcomes. Then, data were analyzed using the chi-square or Fisher's exact method. RESULTS: We identified 29 eligible subjects, including 3 boys and 26 girls. The most common type of thyroid carcinoma was PTC (96.5%), and follicular type (31%) was the predominant variant of PTC. Lymph node involvement occurred in 24% of patients, while distant metastasis occurred in 17.2% of patients with PTC. Twenty-four (82.7%) patients had stage 1 disease. Disease recurrence was recorded in 31% of patients during the study period with a median follow-up time of 24 months. CONCLUSION: PTC is the most frequent type of thyroid carcinoma among children and adolescents. This malignancy has a low mortality rate, but the recurrence rate remains high among younger patients than adults even during a short-term follow-up analysis. Distant metastasis and lymph node involvement are commonly found in this age group.

Analysing 11 years of incidence trends, clinicopathological characteristics, and forecasts of colorectal cancer in young and old patients: a retrospective cross-sectional study in an Indonesian national referral hospital.

OBJECTIVE: To obtain annual incidence trends, understand clinicopathological characteristics, and forecast the future burden of colorectal cancer (CRC) in Indonesia. DESIGN: 11-year retrospective cross-sectional study. SETTING: A national referral hospital in Jakarta, Indonesia. PARTICIPANTS: Data from 1584 eligible cases were recorded for trends and forecasting analyses; 433 samples were analysed to determine clinicopathological differences between young (<50 years) and old (≥50 years) patients. METHODS: Trend analyses were done using Joinpoint software, expressed in annual percentage change (APC), and a regression analysis was executed to generate a forecasting model. Patients' characteristics were compared using χ2 or non-parametric tests. MAIN OUTCOMES: Analysis of trends, forecasting model, and clinicopathological features between the age groups. RESULTS: A significant increase in APC was observed among old patients (+2.38%) for CRC cases. Colon cancer increased remarkably (+9.24%) among young patients; rectal cancer trends were either stable or declining. The trend for right-sided CRC increased in the general population (+6.52%) and old patients (+6.57%), while the trend for left-sided CRC was stable. These cases are expected to be a significant health burden within the next 10 years. Patients had a mean age of 53.17±13.94, 38.1% were young, and the sex ratio was 1.21. Prominent characteristics were left-sided CRC, tumour size ≥5 cm, exophytic growth, adenocarcinoma, histologically low grade, pT3, pN0, inadequately dissected lymph nodes (LNs), LN ratio <0.05, no distant metastasis, early-stage cancer, no lymphovascular invasion, and no perineural invasion (PNI). Distinct features between young and old patients were found in the histological subtype, number of dissected LN, and PNI of the tumour. CONCLUSIONS: Epidemiological trends and forecasting analyses of CRC cases in Indonesian patients showed an enormous increase in colon cancer in young patients, a particularly concerning trend. Additionally, young patients exhibited particular clinicopathological characteristics that contributed to disease severity.

Extragonadal yolk sac tumor following congenital buccal mature cystic teratoma.

Yolk sac tumor (YST) and teratoma both categorized as germ cell tumor (GCT). YST shows preferential differentiation toward yolk sac structures, while teratoma consists of tissues that originate from at least two embryonic germinal layers. Extragonadal location of YST is rare, whereas extragonadal teratoma is majority presented in nasopharynx area. Mature teratoma tends to be benign although some malignant transformation can occur. Recurrence of teratoma was reported mostly in the case of immature teratoma. YST occurrence after removal of mature teratoma is never reported. It is extremely rare for a second GCT to occur at the same site and with a different histological type. We herein report a case of a female infant presented with YST following a congenital buccal mature teratoma.

Short Communication: Few Liver-Infiltrating Cells Express CXCR3 in HIV/HCV Patients Commencing Antiretroviral Therapy.

Coinfections with Hepatitis C virus and human immunodeficiency virus accelerate the progression of both conditions and hamper effective treatment. Here we describe expression of CXCR3 on liver-infiltrating cells and peripheral T cells from coinfected patients commencing antiretroviral therapy (ART) in Indonesia. CXCR3 was expressed by small number of intrahepatic inflammatory cells, mostly in the portal areas. The number of cells did not change on ART and was markedly lower than the number of CD4+ and CD8+ cells in the liver. Data suggest that CXCR3 may contribute to liver infiltration but demonstrate a dynamic situation, changing as the immune system recovers on ART.