Nur Rahadiani

Introduction and importance: Extraosseous mesenchymal chondrosarcoma (MCS) arising in the salivary space is an exceptionally rare malignancy, with only a few cases reported. The rarity of this entity poses significant challenges for clinicians. Case presentation: A 24-year-old female presented with a progressively enlarging mass in the floor of the mouth. Contrast-enhanced magnetic resonance imaging showed a heterogeneously enhancing mass in the left sublingual space with involvement of the genioglossus muscle. Wide local excision via a mandibulotomy approach was performed, with reconstruction using an anterolateral thigh (ALT) free flap. Clinical discussion: Surgical management of MCS in the oral cavity requires careful consideration of the approach and reconstructive options. The mandibulotomy approach provided excellent exposure for complete resection. Reconstruction with an ALT free flap offered soft-tissue coverage with satisfactory functional and esthetic outcomes. Conclusion: This case represents a primary MCS in the sublingual space. Complete surgical resection with long-term surveillance is essential to ensure survival and prevent recurrence.

Introduction : Colorectal cancer (CRC) is the second leading cause of cancer-related death worldwide and ranks among the top three in Indonesia. Most patients were diagnosed in a locally advanced stage, with a high recurrence rate despite standard oxaliplatin-based chemotherapy. The hypoxic tumor microenvironment through activation of HIF-1α and systemic inflammation reflected by the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) could be associated with the tumor progression. Aim : To evaluate the association of HIF-1α expression, NLR, and PLR with three-year progression-free survival (PFS) in locally advanced CRC patients. Methods : This retrospective cohort study included 50 patients with high-risk stage II and stage III CRC who underwent surgical resection and adjuvant oxaliplatin-based chemotherapy in Cipto Mangunkusumo National Hospital. HIF-1α expression was assessed by immunohistochemistry, while NLR and PLR were calculated from pre-treatment blood tests. Data were analyzed using Kaplan–Meier and Cox regression methods, with p Results : The median HIF-1α expression was 96.32%, with a cut-off value of 96.51% (AUC 0.472; p =0.746). There was no significant association between HIF-1α expression and three-year PFS (HR 1.274; p =0.495). The cut-off points for NLR and PLR were 3.46 (AUC 0.486; p =0.872) and 198.31 (AUC 0.505; p =0.952), respectively, and both were not significantly associated with three-year PFS (NLR: HR 0.947; p =0.874; PLR: HR 1.060; p =0.869). Conclusions : HIF-1α expression, NLR, and PLR were not significantly associated with three-year progression-free survival in locally advanced CRC patients.

Early-onset colorectal cancer (EOCRC) is increasingly recognized as a global public health concern. Biomarker research in EOCRC has expanded across hereditary, molecular, epigenetic, liquid biopsy, microbiome, and multi-omics domains, but the overall research landscape remains fragmented. This study aimed to map global research trends and identify prominent and underdeveloped topics in EOCRC biomarker research. A bibliometric analysis was conducted using publications on EOCRC biomarkers retrieved on October 27, 2024. Eligible documents were limited to English-language articles, reviews, and conference proceedings, with a final publication stage and no restriction on publication year. After screening, 134 relevant documents published between 1985 and 2024 were included. Bibliometric indicators, including publication trends, leading contributors, influential publications, topic evolution, and keyword co-occurrence patterns, were analyzed using Biblioshiny (Bibliometrix R package v4.1.3) and VOS viewer (v1.6.18). Early-onset colorectal cancer biomarker research showed steady growth, with an annual growth rate of 7.54% and a publication peak in 2023. The dataset included 134 documents from 92 sources and involved 1,121 authors, with international collaboration observed in 20.9% of publications. Earlier studies focused mainly on hereditary predisposition, Lynch syndrome, mismatch repair genes, and microsatellite instability. More recent research shifted toward molecular profiling, epigenetic alterations, liquid biopsy, gut microbiota, tumor microenvironment, and multi-omics approaches. Underdeveloped areas included diagnostic biomarker validation, screening implementation, gut microbiota, risk factors, and machine learning-based biomarker discovery. Overall, EOCRC biomarker research has evolved from a hereditary-centered focus toward a broader precision oncology framework, but further work is needed to strengthen validation, translational relevance, and clinical applicability across diverse populations.

Introduction Pancreatic malignancy, primarily Pancreatic Ductal Adenocarcinoma (PDAC), presents a significant challenge due to its aggressive nature and late-stage diagnosis. This study explores the role of von Hippel-Lindau gene product (pVHL) in PDAC and non-neoplastic pancreatic tissues, investigating their relationship with PDAC clinicopathological characteristics. Method This research was carried out at the Faculty of Medicine Universitas Indonesia/Dr. Cipto Mangunkusumo General Hospital. The cases analyzed spanned from January 2012 to September 2023. Immunohistochemistry of pVHL was used, and the Histoscore/H-score calculations were utilized to classify pVHL expression as either high or low. Results A total of 54 cases of PDAC and non-neoplastic pancreatic tissue exhibited varying levels of pVHL expression. Cases of PDAC with positive surgical margin, absence of lymphovascular and perineural invasion, pT2, pN0, M0 stage, and survival exceeding 7 months were the profiles in which low pVHL expression was detected. Significant result was found on the correlation between pVHL with pN status. Conclusion The levels of pVHL expression varied between PDAC and non-neoplastic pancreatic tissue. There were no differences in the clinicopathological profile of PDAC tumors, except for pN stage. Further research, with a larger sample size, is needed to determine pVHL's diagnostic value and its expression in different clinicopathological profiles.

Aim: to highlight the diagnostic challenges of Alagille syndrome (AGS), which can mimic other cholestatic diseases like biliary atresia. We aim to emphasize the importance of integrative diagnostic approaches, including genetic testing, to avoid misdiagnosis and unnecessary surgical procedures in cases where histological findings, such as ductular proliferation, do not follow typical patterns of AGS. Key points . Diagnosing Alagille syndrome AGS is quite complex as it shares symptoms similar to those of other cholestatic diseases, especially biliary atresia. Bile duct paucity is the major pattern of AGS. Infants more than six months of age usually already show a visible bile duct paucity. However, in this case, our patient, who was more than six months old, didn’t show bile duct paucity and ductular reaction was the major pattern. A four-year-old girl presented with chronic cholestasis, congenital heart disease, skeletal anomalies, ocular abnormalities, and facial deformity. Her liver biopsy at the age of one year predominantly showed ductular proliferation. Initially, we diagnosed her with biliary atresia. However, subsequent examination of a total hepatectomy sample at the age of four revealed bile ducts were difficult to identify in most portal tracts. Genetic testing in 2022 identified a heterozygous likely pathogenic variant in the JAG1 gene, confirming AGS. The patient underwent liver transplantation. Conclusion. We report the histology findings in AGS that can potentially be mistaken for other cholestatic diseases. We also highlight the importance of integrative diagnostic approaches to avoid misdiagnosis and unwarranted surgical procedures.

Colorectal cancer (CRC) is a major contributor to global cancer mortality. Reliable biomarkers like c-Jun and Interleukin-8 (IL-8) may improve prognosis and therapy. Considering the possible ethnic differences in CRC biomarkers, this study is the first to examine a distinct Southeast Asian cohort (Indonesia). A retrospective study analyzed 98 CRC patients using immunohistochemistry to evaluate c-Jun and IL-8 expression. Paraffin-embedded tissues were assessed for correlations with clinicopathological features. Statistical analyses were performed with p < 0.05 considered significant. c-Jun expression was significantly higher in mucinous or serrated histology (median 1.80, range 0.90-2.30) compared to adenocarcinoma, NOS (median 1.60, range 0.70-2.50) (p = 0.04). Meanwhile, IL-8 expression showed no significant differences across all clinicopathological factors. Neither biomarkers showed significant association with most clinicopathological factors, including age, sex, tumor size, location, stage, grade, invasion, or metastasis. c-Jun and IL-8 expression showed limited prognostic relevance for most clinicopathological features of CRC. However, elevated c-Jun expression may indicate its particular involvement in distinct CRC subtype pathogenesis.

Background: Cell-free DNA (cfDNA) is a fragmented DNA that is released into the blood through necrosis, apoptosis, phagocytosis, or active secretion. cfDNA includes a subclass called circulating tumor DNA (ctDNA) released from cancer cells and constitutes a varied proportion of the total cfDNA. Both cfDNA and ctDNA hold significant potential as diagnostic biomarkers in gastrointestinal cancers. Summary: cfDNA and ctDNA are promising diagnostic biomarkers for gastrointestinal cancers with varied diagnostic values in different types of cancers. cfDNA offers higher sensitivity that makes it more suitable for screening methods and constant monitoring, particularly in integration with conventional biomarkers or in a multimarker model. On the contrary, ctDNA gives a real-time picture of tumor genetics and is more suitable for definitive diagnosis due to its specificity for tumor-associated alterations. Different types of samples and methods of detection can influence sensitivity, and the amount of cfDNA is higher in serum but plasma is used for cfDNA analysis because it contains less cellular contamination. In summary, cfDNA is more sensitive than ctDNA, although they have comparable or slightly lower specificity. Key Message: Further studies are needed to create common guidelines, minimize the cost of analysis, and perform extensive clinical trials to demonstrate the utility of circulating cfDNA and ctDNA in the vast majority of gastrointestinal cancer stages. Therefore, with the advancement in these technologies, cfDNA and ctDNA will be highly beneficial and evolve cancer diagnostics and therapy.

Pancreatic neoplasms exhibit diverse clinical and pathological features, necessitating collaboration between clinicians, radiologists, and anatomical pathologists to enhance diagnostic accuracy and patient management. This study aimed to provide a clinicopathological overview of pancreatic neoplasms in the Indonesian population from 2012 to 2022. A descriptive-analytical cross-sectional study was conducted using secondary data from the Department of Anatomical Pathology, dr. Cipto Mangunkusumo Hospital and electronic medical records. A total of 62 resected pancreatic epithelial neoplasms were analyzed, with solid neoplasms (85%) and cystic neoplasms (15%) predominant. Clinicopathological profiles were associated with neoplasm types based on stage. Pancreatic ductal adenocarcinoma (PDAC), solid pseudopapillary neoplasms (SPN), pancreatic neuroendocrine tumor (PanNET), and pancreatic neuroendocrine carcinoma (PanNEC) were the most common solid neoplasms. Meanwhile, mucinous cystic neoplasm (MCN) was the most common cystic neoplasm. Both solid and cystic neoplasms were more prevalent among women, with 58% of patients under 50 years old. Patients with PDAC and mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) have a higher proportion of <10-month survival rates and advanced stages. Although many clinicopathological features align with existing literature, further research with larger patient cohorts and comprehensive data is warranted.

BackgroundGastrointestinal (GI) cancer is affecting millions of people globally, leading to high incidence and mortality rates and a heavy economic burden. Nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) are a family of cytosolic pattern recognition receptors that regulate host defense responses against microorganisms. Among these, NLR family CARD domain-containing 5 (NLRC5) is assumed to function as a regulator of proinflammatory responses to intracellular pathogens. NLRC5 has been known to regulate immune responses, although its association with cancer remains controversial. This systematic review aimed to explore the roles and functions of NLRC5 in GI cancers. MethodsThree electronic databases, PubMed, Scopus, and ProQuest, were used for literature searching on March 18, 2024. From 921 articles found, 157 duplicates were removed, 671 were excluded based on title and abstract screening, and 84 were excluded based on full-text assessment, resulting in 19 articles included in this review. ResultsElevated NLRC5 levels have been observed in tumor tissues compared to normal tissues across esophageal, gastric, colorectal, and liver cancers. NLRC5 is also associated with increased tumor cell proliferation, migration, and invasion. Cancer cell sensitivity to 5-fluorouracil chemotherapy was found to be negatively correlated with NLRC5 expression. NLRC5 expression levels and genetic variations were also associated with cancer susceptibility to chemotherapeutic drugs and cancer survival. ConclusionNLRC5 potentially exhibits diverse functions in GI cancers, acting as a biomarker for diagnosis, disease progression, prognostic assessment, and determining therapeutic implications. Further investigations are warranted to explore these mechanisms and their potentials for the development of effective treatment of GI cancers.