Current clinical practice in the management of Brazilian patients with potentially resectable pancreatic ductal adenocarcinoma (PDAC).

BACKGROUND AND OBJECTIVES: We aimed to describe the routine clinical practice of physicians involved in the treatment of patients with localized pancreatic ductal adenocarcinoma (PDAC) in Brazil. METHODS: Physicians were invited through email and text messages to participate in an electronic survey sponsored by the Brazilian Gastrointestinal Tumor Group (GTG) and the Brazilian Society of Surgical Oncology (SBCO). We evaluated the relationship between variable categories numerically with false discovery rate-adjusted Fisher's exact test p values and graphically with Multiple Correspondence Analysis. RESULTS: Overall, 255 physicians answered the survey. Most (52.5%) were medical oncologists, treated patients predominantly in the private setting (71.0%), and had access to multidisciplinary tumor boards (MTDTB; 76.1%). Medical oncologists were more likely to describe neoadjuvant therapy as beneficial in the resectable setting and surgeons in the borderline resectable setting. Most physicians would use information on risk factors for early recurrence, frailty, and type of surgery to decide treatment strategy. Doctors working predominantly in public institutions were less likely to have access to MTDTB and to consider FOLFIRINOX the most adequate regimen in the neoadjuvant setting. CONCLUSIONS: Considerable differences exist in the management of localized PDAC, some of them possibly explained by the medical specialty, but also by the funding source of health care.

Reducing time from colon cancer surgery to initiation of adjuvant chemotherapy: pilot project.

Summary: Surgical resection followed by adjuvant chemotherapy is the standard of care for patients with stage III colon cancer. To shorten the time interval between surgery and chemotherapy in patients with colon cancer, we instituted a standardized referral pathway. Evaluation of the intervention demonstrated that referring our patients with colon cancer to a medical oncologist earlier in the treatment process increased the number of patients in whom chemotherapy was initiated within 8 weeks compared with historical controls. These results support early medical oncology referral at institutions where delays in adjuvant chemotherapy initiation exist.

Prognostic factors in patients with malignant pleural effusion: Is it possible to predict mortality in patients with good performance status?

BACKGROUND AND OBJECTIVES: The aim of this study was to identify predictors of mortality only in patients with malignant pleural effusion (MPE) showing good performance status which required pleural palliative procedures. METHODS: All patients with MPE submitted to pleural palliative procedure were enrolled in a prospective study between 2013 and 2014. Patients with Eastern cooperative oncology group (ECOG) score zero, one, and two were considered with good performance status. The possible prognostic factors were tested for significance using the log-rank test (Kaplan-Meier method) and those with significance on univariate analysis were entered into a multivariable Cox model. RESULTS: A total of 64 patients were included in the analysis. Median follow-up time for surviving patients was 263 days. Median survival for the entire cohort was not reached yet. In the multivariate analysis, gastrointestinal primary site (P = 0.006), low albumin concentration in the pleural fluid (P = 0.017), and high serum NLR (P = 0.007) were associated with mortality. CONCLUSION: In our cohort of ECOG 0-2 patients with MPE submitted to pleural palliative procedures, gastrointestinal malignancy compared to other sites, low pleural fluid albumin and high NLR were significantly associated with mortality. The identification of these prognostic factors may assist the choice of the optimal palliative technique. J. Surg. Oncol. 2016;113:570-574. © 2016 Wiley Periodicals, Inc.

Mismatch repair status may predict response to adjuvant chemotherapy in resectable pancreatic ductal adenocarcinoma.

Deficiencies in DNA mismatch repair have been associated with inferior response to 5-FU in colorectal cancer. Pancreatic ductal adenocarcinoma is similarly treated with pyrimidine analogs, yet the predictive value of mismatch repair status for response to these agents has not been examined in this malignancy. A tissue microarray with associated clinical outcome, comprising 254 resected pancreatic ductal adenocarcinoma patients was stained for four mismatch repair proteins (MLH1, MSH2, MSH6 and PMS2). Mismatch repair deficiency and proficiency was determined by the absence or presence of uniform nuclear staining in tumor cells, respectively. Cases identified as mismatch repair deficient on the tissue microarray were confirmed by immunohistochemistry on whole slide sections. Of the 265 cases, 78 (29%) received adjuvant treatment with a pyrimidine analog and 41 (15%) showed a mismatch repair-deficient immunoprofile. Multivariable disease-specific survival in the mismatch repair-proficient cohort demonstrated that adjuvant chemotherapy, regional lymph-node status, gender, and the presence of tumor budding were significant independent prognostic variables (P≤0.04); however, none of the eight clinico-pathologic covariates examined in the mismatch repair-deficient cohort were of independent prognostic significance. Univariable assessment of disease-specific survival revealed an almost identical survival profile for both treated and untreated patients with a mismatch repair-deficient profile, while treatment in the mismatch repair-proficient cohort conferred a greater than 10-month median disease-specific survival advantage over their untreated counterparts (P=0.0018). In this cohort, adjuvant chemotherapy with a pyrimidine analog conferred no survival advantage to mismatch repair-deficient pancreatic ductal adenocarcinoma patients. Mismatch repair immunoprofiling is a feasible predictive marker in pancreatic ductal adenocarcinoma patients, and further prospective evaluation of this finding is warranted.

Claudin 18.2 as a New Biomarker in Gastric Cancer-What Should We Know?

Gastric cancer (GC) remains a formidable global health challenge, ranking among the top-five causes of cancer-related deaths worldwide. The majority of patients face advanced stages at diagnosis, with a mere 6% five-year survival rate. First-line treatment for metastatic GC typically involves a fluoropyrimidine and platinum agent combination; yet, predictive molecular markers have proven elusive. This review navigates the evolving landscape of GC biomarkers, with a specific focus on Claudin 18.2 (CLDN18.2) as an emerging and promising target. Recent phase III trials have unveiled the efficacy of Zolbetuximab, a CLDN18.2-targeting antibody, in combination with oxaliplatin-based chemotherapy for CLDN18.2-positive metastatic GC. As this novel therapeutic avenue unfolds, understanding the nuanced decision making regarding the selection of anti-CLDN18.2 therapies over other targeted agents in metastatic GC becomes crucial. This manuscript reviews the evolving role of CLDN18.2 as a biomarker in GC and explores the current status of CLDN18.2-targeting agents in clinical development. The aim is to provide concise insights into the potential of CLDN18.2 as a therapeutic target and guide future clinical decisions in the management of metastatic GC.

Complete Response to Immunotherapy in a Patient with MUTYH-Associated Polyposis and Gastric Cancer: A Case Report.

MUTYH-associated polyposis syndrome is an uncommon, autosomal recessive colorectal polyposis syndrome caused by biallelic inactivation of MUTYH. Most patients present with multiple colorectal polyps. However, other primary tumor sites have been described as less frequent. In this report, we describe the case of a young patient with a germline biallelic pathogenic MUTYH mutation with three different primary tumors. We focused on a metastatic gastric adenocarcinoma that presented with complete bowel obstruction secondary to extensive peritoneal carcinomatosis and achieved complete response upon treatment with immunotherapy. The patient's tumor presented with a high tumor mutational burden and a 100% combined positive score, which certainly contributed to the complete response to immunotherapy. To date, no studies have described the association of MUTYH-related tumors with high PD-L1 expression, but we hypothesized that it may be linked to the increased antigenicity of these cancers.

Unresectable metastatic colorectal cancer in fit patients - a practical algorithm of treatment sequencing from the Brazilian Group of Gastrointestinal Tumours (GTG).

Recent advances in biomarker-driven therapies have changed the landscape of unresectable metastatic colorectal cancer (mCRC) and brought not only access issues but also difficulties for the treating physician (especially generalist oncologists) in choosing the most suitable treatment for each individual patient. This manuscript proposes an algorithm developed by The Brazilian Group of Gastrointestinal Tumours with the aim of bringing easy-to-follow steps in the management of unresectable mCRC. The algorithm is based on evidence for fit patients to facilitate therapeutic decisions in the clinical practice and assumes that there are no access and resource limitations.

Risk of Cancer in Inflammatory Bowel Disease and Pitfalls in Oncologic Therapy.

BACKGROUND: Inflammatory bowel disease (IBD), represented by ulcerative colitis and Crohn's disease, is an idiopathic condition caused by a dysregulated immune response to host intestinal microflora, leading to chronic relapsing intestinal inflammation. Individuals with IBD are more prone to die from several diseases, including cancer. METHODS: An extensive search was conducted of PubMed using the following medical subject heading-"inflammatory bowel disease" OR "Crohn's disease" OR "ulcerative colitis" AND "cancer." RESULTS: In this review article, we discuss the oncogenic mechanisms and genomics of colitis-associated colorectal cancer. Beyond this, we describe the multiple other malignancies that IBD patients are at risk for, discuss caveats in the screening and diagnosis of those cancers, and shed light on pitfalls on the management and treatment of cancer in IBD patients. CONCLUSION: Patients, caregivers, and health professionals who deal with IBD must be educated on how to identify warning signs so that cancers can be diagnosed and treated as early as possible.

Molecular mechanism of the miR-7/BCL2L1/P53 signaling axis regulating the progression of hepatocellular carcinoma.

Background: To investigate the roles of miR-7 and its potential mechanisms in hepatocellular carcinoma (HCC). Methods: The functions of miR-7 were identified and measured by MTT [3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide], colony formation, transwell, and flow cytometry assays. A luciferase assay was applied to verify the direct binding of miR-7 on BCL2L1 3'untranslated region (3'UTR). An in vitro experiment was then used to investigate the biological effects of miR-7 and BCL2L1. A co-immunoprecipitation (COIP) assay was used to detect the protein interaction between BCL2L1 and P53. Results: We found that miR-7 overexpression suppressed cell proliferation, migration, and invasion in HCC. BCL2L1 was also demonstrated as a direct target gene of miR-7. This study showed that BCL2L1 could partially rescue the inhibitory effect of miR-7 on the proliferation, migration, and invasion of HCC cells. Our research showed that miR-7 could inhibit the epithelial-mesenchymal transition (EMT) pathway by regulating BCL2L1. We also further confirmed that miR-7 inhibits the proliferation, migration, and invasion of Hep3B and Huh7 cells by targeting BCL2L1. Furthermore, we observed that the BCL2L1 protein interacts with the P53 protein and BCL2L1 affects the development of liver cancer through P53. We also found that BCL2L1 could promote the invasion and migration of liver cancer cells through P53 inhibition. BCL2L1 also inhibited the expression of Caspase 3/7 in hepatoma cells by inhibiting the expression of P53. Conclusions: Our study demonstrated that miR-7/BCL2L1/P53 may serve as a regulatory molecular axis for HCC treatment. Our results suggest that miR-7/BCL2L1/P53 may have predictive value and represent a new treatment strategy for liver cancer.

Two-finger digital rectal examination for the diagnosis of anal fistula: protocol for a randomized controlled trial.

Background: Anal fistula is an anorectal infectious disease caused by a perianal abscess or perianal disease. Accurate anorectal examinations are of great significance. The two-finger digital rectal examination (TF-DRE) has been used in clinical practice, with a lack of comprehensive research on the value of the TF-DRE in the diagnosis of anal fistula. This study will compare the difference in the diagnostic value of the TF-DRE, traditional digital rectal examination (DRE), and anorectal ultrasonography in the diagnosis of anal fistula. Methods: For patients who meet the inclusion criteria, a TF-DRE will be performed to explore the number and location of the external and internal orifices, the number of fistulas, and the relationship between the fistula and the perianal sphincter. A DRE and anorectal ultrasonography will also be performed, and the same data will be recorded. To make a comparison, the final diagnosis results of the clinicians during the operation will be taken as the gold standard, the accuracy of the TF-DRE in diagnosing anal fistula will be calculated, and the significance of the TF-DRE in the preoperative diagnosis of anal fistula will be studied and analyzed. All the statistical results will be analyzed using SPSS22.0 (IBM, USA), and a P value <0.05 will be considered statistically significant. Discussion: The research protocol details the advantages of the TF-DRE compared to the DRE and anorectal ultrasonography in the diagnosis of anal fistula. This study will provide clinical evidence of the diagnostic value of the TF-DRE in the diagnosis of anal fistula. Currently, there is a lack of high-quality research using scientific methods on this innovative anorectal examination method. This study will provide rigorously designed clinical evidence on the TF-DRE. Registration: Chinese Clinical Trials Registry ChiCTR2100045450.

Targeting KRAS in Pancreatic Ductal Adenocarcinoma: The Long Road to Cure.

Pancreatic ductal adenocarcinoma (PDAC) remains an important cause of cancer-related mortality, and it is expected to play an even bigger part in cancer burden in the years to come. Despite concerted efforts from scientists and physicians, patients have experienced little improvement in survival over the past decades, possibly because of the non-specific nature of the tested treatment modalities. Recently, the discovery of potentially targetable molecular alterations has paved the way for the personalized treatment of PDAC. Indeed, the central piece in the molecular framework of PDAC is starting to be unveiled. KRAS mutations are seen in 90% of PDACs, and multiple studies have demonstrated their pivotal role in pancreatic carcinogenesis. Recent investigations have shed light on the differences in prognosis as well as therapeutic implications of the different KRAS mutations and disentangled the relationship between KRAS and effectors of downstream and parallel signaling pathways. Additionally, the recognition of other mechanisms involving KRAS-mediated pathogenesis, such as KRAS dosing and allelic imbalance, has contributed to broadening the current knowledge regarding this molecular alteration. Finally, KRAS G12C inhibitors have been recently tested in patients with pancreatic cancer with relative success, and inhibitors of KRAS harboring other mutations are under clinical development. These drugs currently represent a true hope for a meaningful leap forward in this dreadful disease.

PD-L1 testing in advanced gastric cancer-what physicians who treat this disease must know-a literature review.

Background and Objective: Immune checkpoint inhibition has shed light on a new era in cancer therapy, and randomized clinical trials have demonstrated that a meaningful portion of the overall population of metastatic gastric cancer (GC) patients may derive clinical benefit from immunotherapy, which raises the relevance in identifying predictive biomarkers. Programmed cell death-ligand 1 (PD-L1) expression has demonstrated a significant association between level of expression and the magnitude of benefit derived from immune checkpoint inhibition in GC. Nevertheless, this biomarker shows several pitfalls that must be considered in the therapeutic decision to incorporate immune checkpoint inhibition as the standard of care of GC, such as spatial and temporal heterogeneity, interobserver variability, immunohistochemistry (IHC) assay, and influence by chemotherapy or radiation therapy. Methods: In the present comprehensive review, we revised the main studies regarding PD-L1 evaluation in GC. Key Content and Findings: Here we describe the molecular characteristics of the tumor microenvironment in GC, the obstacles in the interpretation of PD-L1 expression and present the data of the clinical trials that have evaluated the efficacy and safety of immune checkpoint inhibition and the association with the biomarker expression, both in first-line and later lines of therapy. Conclusions: From the emerging predictive biomarkers for immune checkpoint inhibition, PD-L1 has demonstrated a meaningful association between level of expression in tumor microenvironment and the magnitude of benefit derived from immune checkpoint inhibition in GC.

A methylation-related signature for predicting prognosis and sensitivity to first-line therapies in gastric cancer.

Background: Methylation modification patterns play a crucial role in human cancer progression, especially in gastrointestinal cancers. We aimed to use methylation regulators to classify patients with gastric adenocarcinoma and build a model to predict prognosis, promoting the application of precision medicine. Methods: We obtained RNA sequencing data and clinical data from The Cancer Genome Atlas (TCGA) database (n=335) and Gene Expression Omnibus (GEO) database (n=865). Unsupervised consensus clustering was used to identify subtypes of gastric adenocarcinoma. We performed functional enrichment analysis, immune infiltration analysis, drug sensitivity analysis, and molecular feature analysis to determine the clinical application for different subtypes. The univariate Cox regression analysis and the LASSO regression analysis were subsequently used to identify prognosis-related methylation regulators and construct a risk model. Results: Through unsupervised consensus clustering, patients were divided into two subtypes (cluster A and cluster B) with different clinical outcomes. Cluster B included patients with a better prognosis outcome and who were more likely to respond to immunotherapy. We then successfully built a predictive model and found five methylation-related genes (CHAF1A, CPNE8, PHLDA3, SPARC, and EHF) potentially significant to the prognosis of patients. The 1-, 3-, and 5-year areas under the curve of the risk model were 0.712, 0.696, and 0.759, respectively. The risk score was an independent prognostic factor and had the highest concordance index among common clinical indicators. Meanwhile, the tumor microenvironment, sensitivity of chemotherapeutic drugs, molecular features, and oncogenic dedifferentiation differed significantly across the risk groups and subtypes. Conclusions: We classified patients with gastric adenocarcinoma based on methylation regulators, which has positive implications for first-line clinical treatment. The prognostic model could predict the prognosis of patients and help to promote the development of precision medicine.

Should we still be using bolus 5-FU prior to infusional regimens in gastrointestinal cancers? A practical review.

5-fluorouracil (5-FU), a pyrimidine analogue with antimetabolite activity, is one of the most widely used drugs in Oncology and many different regimens have been described regarding its use. Nowadays, the modified de Gramont is the most popular schedule of 5-FU to treat gastrointestinal cancers and may be given either alone or combined with irinotecan, oxaliplatin and monoclonal antibodies. The true clinical value of bolus 5-FU right before infusional regimens remains to be determined since no randomized trials have addressed this issue. This manuscript aims to review the history of 5-FU, its mechanism of action and the data exploring the role of bolus 5-FU.

Biomarkers in Anal Cancer: Current Status in Diagnosis, Disease Progression and Therapeutic Strategies.

Squamous cell carcinoma of the anal canal (SCCA) is a rare neoplasm, but with rising incidence rates in the past few decades; it is etiologically linked with the human papillomavirus (HPV) infection and is especially prevalent in immunocompromised patients, mainly those infected with HIV. Fluoropyrimidine-based chemoradiotherapy remains the cornerstone of the treatment of non-metastatic disease, but the locally advanced disease still presents high rates of disease recurrence and systemic therapy of SCCA is an unmet clinical need. Despite sharing common molecular aspects with other HPV-related malignancies, such as cervical and head and neck cancers, SCCA presents specific epigenomic, genomic, and transcriptomic abnormalities, which suggest that genome-guided personalized therapies should be specifically designed for this disease. Actionable mutations are rare in SCCA and immune checkpoint inhibition has not yet been proven useful in an unselected population of patients. Therefore, advances in systemic therapy of SCCA will only be possible with the identification of predictive biomarkers and the subsequent development of targeted therapies or immunotherapeutic approaches that consider the unique tumor microenvironment and the intra- and inter-tumoral heterogeneity. In the present review, we address the molecular characterization of SCCA and discuss potential diagnostic, predictive and prognostic biomarkers of this complex and challenging disease.

Localized Well-Differentiated Rectal Neuroendocrine Tumors - Where Are We in 2021?

Neuroendocrine tumors (NETs) are slow-growing malignancies with distinct biologic and clinical characteristics. Most rectal-NETs are localized and well-differentiated, usually carrying an excellent prognosis. In this review, we aim at describing the epidemiology, clinical characteristics and therapeutic approaches for well-differentiated rectal NETs.

Glycolysis-related gene dihydrolipoamide acetyltransferase promotes poor prognosis in hepatocellular carcinoma through the Wnt/ß-catenin and PI3K/Akt signaling pathways.

Background: Recent research suggests that dihydrolipoamide acetyltransferase (DLAT), which is a copper-induced cell death-related gene, is involved in multiple biological events in tumors. This study sought to investigate the relationship between DLAT and hepatocellular carcinoma (HCC). Methods: In the Cancer Genome Atlas (TCGA) database, we first identified the differentially expressed gene (i.e., DLAT), then confirmed DLAT expression, and found a link between it and the prognosis of HCC patients. An internal validation nomogram was built based on a multivariate Cox regression analysis. Data from the Tumor Immune Estimation Resource (TIMER) database was used to examine the association between DLT and immunological cells. A gene set enrichment analysis (GSEA) was conducted to investigate the probable mechanism of action. Finally, in vitro cytological research was conducted to further examin the involvement of DLAT in HCC-related unfavorable biological events. Results: The database screenings showed that DLAT was a differentially expressed molecule; that is, DLAT was more highly expressed in the cancer tissues than normal tissues. TCGA results and Kaplan-Meier-plotter data sets showed that HCC patients with reduced DLAT expression had greater disease-specific survival (DSS), overall survival (OS), and progression-free interval (PFI). The prediction model had a concordance index of 0.659 (0.614-0.704), which indicates high accuracy. According to the TIMER database, tumor cells in the HCC microenvironment may be able to bypass the immune system due to the expression of DLAT. The in vitro cytological tests showed that DLAT knockdown significantly decreased the proliferation and invasion of the HCC cells. It also inhibited the activity of the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/protein kinase B (Akt) and Wnt/ß-catenin signaling pathways. Conclusions: Decreased DLAT expression significantly prolongs the OS, PFI, and DSS of HCC patients. DLAT may be employed as a new predictive biomarker for HCC, and may be linked to the immune system in HCC patients. The tumor microenvironment (TME) may have a significant effect on the ability of tumor cells to evade the immune system. The PI3K/Akt and Wnt/ß-catenin signaling pathways may affect the prognosis of HCC by interfering with DLAT. Given these findings, HCC may be an ideal target for the development of anti-cancer therapies.

Current Molecular Profile of Gastrointestinal Stromal Tumors and Systemic Therapeutic Implications.

Gastrointestinal stromal tumors (GISTs) are malignant mesenchymal tumors arising from the intestinal pacemaker cells of Cajal. They compose a heterogenous group of tumors due to a variety of molecular alterations. The most common gain-of-function mutations in GISTs are either in the KIT (60-70%) or platelet-derived growth factor receptor alpha (PDGFRA) genes (10-15%), which are mutually exclusive. However, a smaller subset, lacking KIT and PDGFRA mutations, is considered wild-type GISTs and presents distinct molecular findings with the activation of different proliferative pathways, structural chromosomal and epigenetic changes, such as inactivation of the NF1 gene, mutations in the succinate dehydrogenase (SDH), BRAF, and RAS genes, and also NTRK fusions. Currently, a molecular evaluation of GISTs is imperative in many scenarios, aiding in treatment decisions from the (neo)adjuvant to the metastatic setting. Here, we review the most recent data on the molecular profile of GISTs and highlight therapeutic implications according to distinct GIST molecular subtypes.

Biologics in rectal cancer.

INTRODUCTION: Despite the use of multimodality therapy, locally advanced rectal cancer (LARC) still presents high rates of disease recurrence. Fluoropyrimidine-based chemotherapy concurrently with radiation therapy (RT) remains the cornerstone of neoadjuvant therapy of LARC, and novel therapies are urgently needed in order to improve the clinical outcomes. AREAS COVERED: We aim to summarize data from completed and ongoing clinical trials addressing the role of biological therapies, including monoclonal antibodies, immune checkpoint inhibitors (ICIs), antibody-drug conjugates, bispecific antibodies, and gene therapies in the systemic therapy of rectal cancer. EXPERT OPINION: Deeper understanding of the molecular biology of colorectal cancer (CRC) has allowed meaningful advances in the systemic therapy of metastatic disease in the past few years. The larger applicability of biological therapy in CRC, including genome-guided targeted therapy, antiangiogenics, and immunotherapy, gives us optimism for the personalized management of rectal cancer. Microsatellite instability (MSI) tumors have demonstrated high sensitivity to ICIs, and preliminary findings in the neoadjuvant setting of rectal cancer are promising. To date, antiangiogenic and anti-EGFR therapies in LARC have not demonstrated the same benefit seen in metastatic disease. The outstanding results accomplished by biomarker-guided therapy in metastatic CRC will guide future developments of biological therapy in LARC.

Synchronous duodenal neuroendocrine neoplasm and congenital factor XIII deficiency: case report and review of the literature.

Background: Neuroendocrine neoplasms (NENs) are uncommon, with duodenal NENs (dNENs) being particularly rare in clinical practice. Congenital factor XIII deficiency (FXIIID) is also an extremely rare hematological disease in which poor wound healing may occur due to coagulopathy. The concurrent occurrence of these two rare diseases has not been reported before, which increases the difficulty of diagnosis and treatment. This is the first report of dNEN concomitant with Congenital FXIIID, which can present as a reference for clinicians who may encounter similar situations in the future. Case Description: We report a 33-year-old woman with bleeding diathesis since childhood who complained of digestive tract bleeding for 7 years. She was finally diagnosed as duodenal neuroendocrine neoplasm combined with congenital factor XIII deficiency. The patient underwent surgery, and pathological findings confirmed neuroendocrine tumor. After surgery she received cryoprecipitate and fresh frozen plasma (FFP) therapy. No tumor recurrence has been observed nor recurrence of digestive tract bleeding during the 2-year follow-up. Conclusions: Our report suggests when gastrointestinal bleeding is difficult to explain, more general examinations in addition to gastroscopy should be performed. In situations where digestive tract bleeding cannot be fully explained by a single disease, the possibility of concomitant disease, such as hematological disorders, should be considered to avoid the missed diagnosis of rare co-morbidities.