Impact of time from diagnosis to chemotherapy on prognosis in advanced pancreatic cancer.

BACKGROUND: Due to the aggressive nature and poor prognosis of advanced pancreatic cancer, prompt initiation of treatment is critical. We investigated the effect of the interval between cancer diagnosis and initiation of chemotherapy on survival in patients with advanced pancreatic cancer. METHODS: In this retrospective, single-centre study, consecutive patients with advanced pancreatic cancer between April 2013 and March 2022 were analyzed. Data were extracted from the electronic medical records of patients who received chemotherapy for metastatic, locally advanced or resectable pancreatic cancer or who received chemotherapy due to either being intolerant of or declining surgery. We compared overall survival between two groups: the early waiting time group (waiting time ≤30 days from diagnosis to chemotherapy initiation) and the elective waiting time group (waiting time ≥31 days). Prognostic factors, including biliary drainage, were considered. The impact of waiting time on survival was assessed by univariate and multivariate analyses with Cox proportional hazard models. A 1:1 propensity score matching approach was used to balance bias, accounting for significant poor prognosis factors, age and sex. RESULTS: The study involved 137 patients. Overall survival exhibited no statistically significant difference between the early and elective waiting time groups (207 and 261 days, P = 0.2518). Univariate and multivariate analyses identified poor performance status and metastasis presence as predictors of worse prognosis. This finding persisted post propensity score matching (275 and 222 days, P = 0.8223). CONCLUSIONS: Our study revealed that initiating chemotherapy ˃30 days later does not significantly affect treatment efficacy compared to within 30 days of diagnosis.

Impact of Initial Body Weight Loss on Prognosis in Advanced Pancreatic Cancer: Insights From a Single-Center Retrospective Study.

BACKGROUND: Pancreatic cancer (PC) has a poor prognosis, with body weight loss commonly observed at diagnosis. However, the impact on PC prognosis of weight loss at the time of diagnosis on PC prognosis is unknown. METHODS: This retrospective, single-center study enrolled consecutively patients diagnosed with metastatic or locally advanced PC or resectable PC who were intolerant of or refused surgery. Patients who had lost more than 5% of their body weight or more than 2% and had a body mass index (BMI) of less than 20 kg/m2 at diagnosis were classified as experiencing body weight loss. Patients were subclassified into 2 groups: patients with and without weight loss. The study evaluated patient-related and PC-related factors affecting prognosis. Cox proportional hazards models were used to assess factors affecting prognosis. The primary endpoint was overall survival. Additionally, 1:1 propensity score matching was performed to reduce bias. RESULTS: In total, 220 patients were included in the study. The median age of the patients was 74 years, and 49.1% were male. Weight loss at diagnosis was observed in 43.2% of patients. There were no significant differences in clinical factors, except for anthropometric parameters, between the groups. The median survival time did not differ between the weight loss and no weight loss groups (149 and 173 days, respectively, P = .669). After matching, no significant differences in survival times were observed between the 2 groups. CONCLUSIONS: This study found no association between weight loss at diagnosis and prognosis in patients with advanced PC treated with best supportive care or chemotherapy.

Stratification Based on Risk Factors at Diagnosis Could Predict Progression in Patients with Pancreatic Cysts.

BACKGROUND: Predicting the risk of malignant transformation in pancreatic cyst patients is challenging. AIM: We retrospectively investigated the risk factors for malignant transformation in pancreatic cyst patients. METHODS: Patients with pancreatic cysts diagnosed using imaging tests were followed from November 2008 to December 2021. A significant change was defined as the additional development of high-risk stigmata (HRS), worrisome features (WFs), or pancreatic cancer during monitoring. RESULTS: In total, 479 patients were analyzed, with a median observation period of 50 months. Forty-four patients (9.2%) showed significant changes, and eight (1.7%) developed pancreatic cancer. The univariate analysis showed that the cyst diameter at diagnosis (≥ 14 mm), main pancreatic duct (MPD) diameter at diagnosis (≥ 3 mm), presence of multilocular cysts, and an inconsistent MPD caliber were significant predictive factors for a significant change. One point was assigned for each significant factor. We grouped the patients into three groups: the low-risk group (total score 0), medium-risk group (score 1-2), and high-risk group (score 3-4). The high-risk group had a higher risk of a significant change than the medium- and low-risk groups (age-adjusted HRs for the medium-risk and high-risk groups were 3.0 and 5.2 compared with the low-risk group). CONCLUSION: Stratification based on risk factors may help predict the development of significant changes in pancreatic cyst patients.

Predictive factors of collateral vessel development induced by oxaliplatin-based chemotherapy.

BACKGROUND AND AIM: Oxaliplatin can lead to hepatic sinusoidal injury, called hepatic sinusoidal obstruction syndrome (SOS), resulting in portal hypertension-related complications. This could worsen the clinical course of the patients treated with oxaliplatin. Early diagnosis is challenging. We explored predictive markers of oxaliplatin-induced collateral vessels. METHODS: Patients who received oxaliplatin-based chemotherapy were retrospectively screened. We evaluated their laboratory findings and spleen size on computed tomography immediately before oxaliplatin-based chemotherapy and after 6 months of treatment. The primary outcome was collateral vessel development, as a surrogate marker for oxaliplatin-induced SOS in patients who underwent oxaliplatin-based chemotherapy. The secondary outcome was the identification of factors that predicted the development of collateral vessels. RESULTS: We enrolled 161 patients who received oxaliplatin-based chemotherapy. They had a median age of 69 years, and 63.3% were men. Collateral vessels developed in nine (5.6%) patients during the study period. After oxaliplatin-based chemotherapy, the spleen size increased in 104 patients (64.6%), with a ≥ 30% increase in 19.4% of the patients. Univariate analysis showed that the Fibrosis-4 (FIB-4) index (≥ 1.76; OR 9.17), aspartate aminotransferase:platelet ratio index (APRI) (≥ 0.193; OR 9.62), cumulative dose of oxaliplatin (≥ 1000 mg; OR 8.43), and increase in spleen size (≥ 30%; OR 6.01) were significant risk factors for collateral vessel development. Multivariate analysis after stepwise selection revealed that the FIB-4 index and spleen size were significant independent predictive factors. CONCLUSION: A ≥ 1.76 increase in the FIB-4 index and a ≥ 30% increase in spleen size after 6 months of oxaliplatin-based chemotherapy were significant predictive markers for collateral vessel development.

Classification and clinical features of adverse drug reactions in patients with ulcerative colitis treated with 5-aminosalicylate acid: a single-center, observational study.

BACKGROUND: 5-Aminosalicylate acid (5-ASA) is a crucial drug for ulcerative colitis (UC) patients. 5-ASA has several side effects. However, the types of side effects vary and are sometimes severe. METHODS: A single-center, retrospective cohort study was conducted from September 2001 to June 2020. We surveyed consecutive UC patients who visited our hospital and investigated adverse drug reactions (ADRs) related to 5-ASA formulations. We grouped patients into four subgroups: (1) lupus-like symptoms, (2) blood test abnormalities, (3) mimicking IBD exacerbation and (4) others. Their clinical courses were evaluated. RESULTS: We surveyed 288 consecutive UC patients, 35 of whom developed ADRs of any grade (12.9%), and analyzed 27 patients. The median age and 5-ASA doses were 43 years and 4000 mg, respectively, and 48% were male. The ADR triggers were the first use of 5-ASA (n = 17, 63%), 5-ASA switch (n = 9, 33%) and 5-ASA dose escalation (n = 1, 3.7%). The median time to ADR was 15 days (IQR: 7, 63). Ten patients (37%) had grade 3/4 ADRs. Fever was the most common ADR (n = 6, 23%), followed by hyperamylasemia and headache (n = 4, 15%). Lupus-like symptoms accounted for 56% (n = 15), blood test abnormalities for 26% (n = 7), mimicking IBD exacerbation for 15% (n = 4) and others for 3.7% (n = 1). The time to ADR was shorter in the mimicking IBD exacerbation group (median 11 days) than in the lupus-like symptoms (22 days) and blood test abnormalities (55 days) groups. CONCLUSION: Classification of ADRs related to 5-ASA into four groups might lead to early recognition of ADRs.

Time Trend of the Radiation Exposure Dose in Endoscopic Retrograde Cholangiopancreatography Over an 8-Year Period: A Single-Center Retrospective Study.

INTRODUCTION: The global needs for a reduction in radiation exposure (RE) are increasing. Endoscopic retrograde cholangiopancreatography (ERCP) is a significant fluoroscopic procedure in the gastrointestinal field. However, the actual RE in ERCP and its annual trend are still unclear. Therefore, we examined the yearly trend of RE in ERCP. METHODS: This retrospective, single-center cohort study included consecutive cases of ERCP from September 2012 to June 2019. We measured the air kerma (AK, mGy), dose area product (DAP, Gycm2), and fluoroscopy time (FT, min). We also evaluated the annual trend of the RE before and after the fluoroscopy device update. RESULTS: In total, 2,174 patients receiving ERCP were enrolled. Among these, the mean age was 74.3 years, and 913 patients were women (42.0%). The median/third quartile values of AK (mGy), DAP (Gycm2), and FT (min) were 109/234 mGy, 13.3/25.8 Gycm2, and 18.2/27.7 minutes. The annual AK, DAP, and FT from 2012 to 2019 were 138, 207, 173, 177, 106, 71.0, 45.0, and 33.3 mGy; 23, 21.4, 19, 18.3, 11.9, 9.0, 6.8, and 6.4 Gycm2; and 12.5, 12.1, 9.7, 9.8, 8.2, 10.8, 9.4, and 10.3 minutes, respectively. The corresponding values before and after the update in July 2016 were 177 and 52 mGy (P < 0.0001), 19.2 and 7.6 Gycm2 (P < 0.0001), and 10.2, and 9.9 minutes (P = 0.05), respectively. DISCUSSION: The RE from ERCP tended to decrease every year, especially after fluoroscopy device updates.

Vascular endothelial growth factor-A is an Immunohistochemical biomarker for the efficacy of bevacizumab-containing chemotherapy for duodenal and jejunal adenocarcinoma.

BACKGROUND: The efficacy and safety of bevacizumab-containing chemotherapy for patients with metastatic duodenal and jejunal adenocarcinoma (mDJA) are unclear. The present study aimed to evaluate the efficacy of bevacizumab and to explore immunohistochemical markers that can predict the efficacy of bevacizumab for patients with mDJA. METHODS: This multicentre study included patients with histologically confirmed small bowel adenocarcinoma who received palliative chemotherapy from 2008 to 2017 at 15 hospitals. Immunostaining was performed for vascular endothelial growth factor-A (VEGF-A), TP53, Ki67, ß-catenin, CD10, MUC2, MUC5AC, MUC6, and mismatch repair proteins. RESULTS: A total of 74 patients were enrolled, including 65 patients with mDJA and 9 with metastatic ileal adenocarcinoma. Patients with mDJA who received platinum-based chemotherapy with bevacizumab as first-line treatment tended to have a longer progression-free survival and overall survival than those treated without bevacizumab (P = 0.075 and 0.077, respectively). Multivariate analysis extracted high VEGF-A expression as a factor prolonging progression-free survival (hazard ratio: 0.52, 95% confidence interval: 0.30-0.91). In mDJA patients with high VEGF-A expression, those who received platinum-based chemotherapy with bevacizumab as a first-line treatment had significantly longer progression-free survival and tended to have longer overall survival than those treated without bevacizumab (P = 0.025 and P = 0.056, respectively), whereas no differences were observed in mDJA patients with low VEGF-A expression. CONCLUSION: Immunohistochemical expression of VEGF-A is a potentially useful biomarker for predicting the efficacy of bevacizumab-containing chemotherapy for patients with mDJA.

HEG1-responsive microRNA-23b regulates cell proliferation in malignant mesothelioma cells.

Malignant mesothelioma (MM) is a fatal tumor, and the absence of a specific diagnostic marker and/or a pathogenic molecule-targeting drug is a major issue for its pathological diagnosis and for targeting therapy. The molecular target of MM has not been elucidated because of unknown survival, death, and cytotoxic signals in MM. HEG homolog 1 (HEG1) is a mucin-like membrane protein that contains epidermal growth factor-like domains, and it plays an important role in cancers through aberrant signaling, including that during cell adhesion, as well as through protection from invasion of tumor cells. HEG1 expression supports the survival and proliferation of MM cells. In this study, functional analysis of HEG1 and microRNAs using MM cell lines (H226, MESO4, H2052) was performed. The MTS assay revealed that cell proliferation was significantly reduced upon transient transfection with microRNA-23b (miR-23b) inhibitor and/or HEG1 siRNA. The Annexin V assay revealed that apoptosis was induced upon suppression of miR-23b and/or HEG1. Western blotting showed that the autophagy-related protein LC3-II was induced upon suppression of miR-23b and/or HEG1. These results revealed that miR-23b contributes to HEG1-dependent cell proliferation through evasion of cytotoxicity induced by apoptosis and autophagy in MM cells. HEG1-dependent/mediated miR-23b signaling may therefore be a potential target for MM diagnosis and therapy.

A Triple-Drug Blister-Packaged Drug with Vonoprazan Improves First-Line Eradication of Helicobacter pylori in Elderly Patients: A Retrospective Propensity Score-Matched Cohort Study.

BACKGROUND: A blister-packaged drug might be useful to enhance the eradication of Helicobacter pylori. We investigated the effect of a blister-packaged drug for H. pylori eradication. METHODS: We treated 1,758 patients with H. pylori infections and evaluated the successful eradication rate in patients who underwent first-line eradication between January 2013 and May 2018. Treatments included a conventional proton pump inhibitor (PPI) blister-packaged drug containing lansoprazole or rabeprazole with clarithromycin (CAM) and amoxicillin (AC), vonoprazan (VPZ) with CAM and AC in a separate tablet, or a VPZ blister-packaged drug (VONOSAP) containing VPZ with CAM and AC, with all drugs given twice daily for 7 days. RESULTS: Finally, we evaluated 1,263 patients (conventional PPI: n = 644, VPZ: n = 326, and VONOSAP: n = 293). The overall successful eradication rates were 71.9% in the conventional PPI group, 90.2% in the VPZ group, and 92.2% in the VONOSAP group. There was a significantly lower eradication rate in the PPI group than in the VPZ and VONOSAP (p < 0.00001, p < 0.0001) groups, but there was no significant difference between the VPZ and VONOSAP groups (p = 0.4006). We enrolled a total of 256 age- and gender-matched patients in the VPZ and VONOSAP groups, and both groups had successful eradication rates of approximately 90% (89.8 vs. 90.4%, respectively, p = 0.7641). After analyzing the subgroup of patients older than 75 years, there was a significant treatment benefit of VONOSAP but not of VPZ in elderly patients (EPs). CONCLUSION: Triple-drug blister-packaged drugs including VPZ may improve the first-line eradication of H. pylori in EPs.

Evaluation of DNA and RNA quality from archival formalin-fixed paraffin-embedded tissue for next-generation sequencing - Retrospective study in Japanese single institution.

Genetic analysis on formalin-fixed paraffin-embedded (FFPE) tissue specimens has become a mainstream method, from conventional direct sequencing to comprehensive analysis using next-generation sequencing (NGS). In this study, we evaluated the quality of DNA and RNA extracted from FFPE sections, derived from surgical specimens of different tumor types. Electrophoresis was performed using a 4200 TapeStation to evaluate DNA and RNA fragmentation. DNA Ct values were higher and significantly increased over a period of 4 years compared with those from cell lines or frozen tissues. The RNA integrity number equivalent (RIN) ranged from 1 to 4.1 and DV200 ranged from 7.3 to 81%. Twelve of the 108 cases were analyzed by NGS using the AmpliSeq Cancer HotSpot Panel v2 on a Miniseq system. A sufficient number of reads and coverage were obtained in all cases. Our results revealed that NGS analysis was sufficient for FFPE-derived DNA within 4 years of preservation. Conversely, approximately 20% of the RNA derived from FFPE within 4 years from the collection could be inappropriate for gene analysis based on RIN and DV200. It was suggested that FFPE would be adequate for genetic analysis, although it is desirable to store frozen specimens for the tumor tissues to be subjected to genetic analysis.

Distinct Clinical Factors in Hospitalized Patients with Diverticular Bleeding and Diverticulitis.

BACKGROUND/AIMS: It is unclear why colonic diverticular bleeding and diverticulitis rarely coexist. This study compared the characteristics of these conditions. METHODS: This single-center retrospective study examined 310 consecutive patients hospitalized with an episode of diverticular disease (cases) and outpatients without a diverticular episode (controls) from January 2012 to December 2015. We investigated distinct clinical factors in hospitalized patients with diverticular bleeding and diverticulitis. RESULTS: We identified 183 patients with 263 episodes of diverticular bleeding and 127 patients with 135 episodes of diverticulitis during the study period. Patients with diverticular bleeding were significantly older than those with diverticulitis (median age 76 vs. 56 years) and had more cardiovascular disease, hypertension, diabetes, cerebrovascular disease, chronic kidney disease, lipid disorder, or a poorer performance status. Significantly more diverticular bleeding patients were taking antiplatelet drugs, anticoagulant drugs, proton pump inhibitors, or laxative agents. Multivariate analysis revealed that an age > 65 years (OR 5.42), and antiplatelet agent use (OR 7.29) were more significant risk factors for diverticular bleeding than for diverticulitis. CONCLUSIONS: Elderly people using antiplatelet drugs may be more susceptible to diverticular bleeding than diverticulitis.

Efficacy of chemotherapy for older patients with gastric cancer: a multicenter retrospective cohort study.

BACKGROUND: Gastric cancer is one of the leading causes of malignant disease-related mortality, worldwide. With the use of recently developed anti-tumor agents, the prognoses of patients with unresectable gastric cancer are improving. However, the development of an aggressive treatment strategy for older patients (OPs) remains under debate due to concerns regarding treatment feasibility or patient frailty. We aimed to elucidate whether aggressive chemotherapy has survival benefits for OPs with advanced gastric cancer. METHODS: We analyzed consecutive patients diagnosed with inoperable advanced gastric cancer across seven hospitals from August 2007 to July 2015. We defined OPs as patients aged 75 years or older and compared their survival rates with those of non-older patients (NPs). RESULTS: A total of 256 OPs and 425 NPs were enrolled. Of the OPs, 152 patients received chemotherapy and 104 patients received best supportive care (BSC). In contrast, among the NPs, 375 patients received chemotherapy and 50 patients received BSC. There was no significant difference of the median survival time between OPs and NPs in the response to BSC (61 vs 43 days) or chemotherapy (312 vs 348 days). Combination chemotherapy significantly improved survival compared to monotherapy in both OPs and NPs groups (382 vs 253 days in OPs, 381 vs 209 days in NPs). Good performance status, combination therapy, and male, but not age, were significant independent prognostic factors. CONCLUSION: When the performance status of a gastric cancer patient is good, active chemotherapy may improve survival, regardless of age.

Glucosamine Suppresses Osteoclast Differentiation through the Modulation of Glycosylation Including O-GlcNAcylation.

Osteoclasts represent the only bone resorbing cells in an organism. In this study, we investigated the effect of glucosamine (GlcN), a nutrient used to prevent joint pain and bone loss, on the osteoclastogenesis of murine macrophage-like RAW264 cells. GlcN supplementation suppressed the upregulation of osteoclast-specific genes (tartrate-resistant acid phosphatase (TRAP), cathepsin K, matrix metallopeptidase 9, and nuclear factor of activated T cell c1 (NFATc1)), receptor activator of nuclear factor-κB ligand (RANKL)-dependent upregulation of TRAP enzyme activity, and the formation of TRAP-positive multinuclear cells more effectively than N-acetylglucosamine (GlcNAc), which we have previously shown to inhibit osteoclast differentiation. To clarify the mechanism by which GlcN suppresses osteoclastogenesis, we further investigated the effect of GlcN on O-GlcNAcylation by Western blotting and on other types of glycosylation by lectin blotting. We found that, upon addition of GlcN, the O-GlcNAcylation of cellular proteins was increased whereas α2,6-linked sialic acid modification was decreased. Therefore, these glycan modifications in cellular proteins may contribute to the suppression of osteoclastogenesis.

[Squamous cell carcinoma of the anal canal treated with chemoradiotherapy in a patient with HIV].

Since the introduction of combination antiretroviral therapy (ART), the life expectancy has increased for patients infected with human immunodeficiency virus (HIV). This has been associated with reductions in the incidences of some AIDS-defining malignancies, such as Kaposi sarcoma and non-Hodgkin lymphoma, but has coincided with an increased incidence of non-AIDS-defining malignancies, such as anal cancer. However, anal cancers are rare in patients with HIV in Japan. We report the case of an HIV-infected patient with anal cancer treated with chemoradiotherapy. A 37-year-old man receiving ART for HIV infection presented with a 1-month history of left inguinal lymphadenopathy and anal pain. Magnetic resonance imaging and computed tomography revealed a 56-mm mass, left inguinal lymphadenopathy, and left external iliac lymphadenopathy. The mass had infiltrated from the anal canal to the right levator ani and corpus spongiosum. Colonoscopy revealed a tumor with an ulcer in the anal canal. Histological examination of the tumor biopsy specimens confirmed the diagnosis of squamous cell carcinoma. The patient was diagnosed with anal cancer (T4N2M1 stage IV), and he received 5-fluorouracil (1000mg/m(2) on days 1-4 and 29-32) plus mitomycin C (10mg/m(2) on days 1 and 29) and concurrent radiotherapy (total dose, 59.4Gy in 33 fractions) along with ART. The treatment-related adverse events were grade 4 leukopenia and neutropenia, grade 3 thrombocytopenia, and grade 2 radiation dermatitis. Moreover, CD4 suppression was observed:the CD4 count decreased from 190 cells/µl before chemoradiotherapy to 138 cells/µl after 3 months, but increased to 210 cells/µl after 1 year. Because of the grade 4 leukopenia and neutropenia, the dose of 5-fluorouracil was reduced to 800mg/m(2) on days 29-32. A complete response was confirmed on magnetic resonance imaging, and colonoscopy confirmed the disappearance of the anal cancer. The patient is living with no signs of recurrence at 2 years after chemoradiotherapy. When treating HIV-infected patients with anal cancer by chemoradiotherapy and ART, clinicians should be aware of the possibility of CD4 suppression.

Administration of low-dose epoetin-alpha facilitates adherence to ribavirin in triple therapy with pegylated interferon-alpha-2b and telaprevir.

AIM: Anemia frequently develops in patients given pegylated interferon, ribavirin (RBV), telaprevir (TVR) triple therapy and restricts treatment by forcing reduction or discontinuation of RBV administration. We investigated whether erythropoietin (EPO) could alleviate RBV-induced anemia to help maintain the RBV dose during the first 12 weeks, the triple therapy phase. METHODS: Twenty-two patients with hepatitis C virus (HCV) genotype 1 were enrolled. Hemoglobin (Hb) concentration was measured every week. If Hb reduction from the baseline was 2 g/dL or more, 12 000 IU of epoetin-α was administrated. When further reduction (≥3 g/dL) was observed, 24 000 IU of epoetin-α was used. Inosine triphosphatase (ITPA) single nucleotide polymorphism (rs1127354) was genotyped for all patients. RESULTS: Among the 22 patients enrolled in this study, three required RBV dose reduction due to anemia, two had to discontinue or reduce TVR and RBV due to creatinine elevation. The remaining 17 patients completed the treatment during the triple therapy phase without reduction of the RBV dose or adverse events attributable to EPO. Regardless of ITPA genotype, Hb decline was well controlled by EPO administration, whereas the total EPO dose tended to be higher in the CC genotype group. The average adherence to RBV during the triple therapy phase was 97.5%. SVR was achieved in 17 patients; two patients had viral breakthrough and three patients had relapse of HCV RNA. CONCLUSION: EPO can be a favorable alternative to reduction of RBV to facilitate the adherence of patients on TVR-based triple therapy.

Colonic diverticular bleeding due to a rupture of an ileocolic artery pseudoaneurysm secondary to colonic diverticulitis.

A 53-year-old woman with a history of recurrent right lower quadrant pain presented with slightly bloody stools in April 2023. She was initially diagnosed with acute diverticulitis using an abdominal computed tomography (CT) scan and was treated conservatively. On the second day, however, she reported significant hematochezia. A subsequent contrast-enhanced CT scan revealed an extravasation in the ascending colon, which was promptly managed with colonoscopy. Despite initial hemostasis, she experienced recurrent bleeding. Another contrast-enhanced CT scan revealed a pseudoaneurysm with ongoing extravasation in the same area. Angiography confirmed a pseudoaneurysm in a branch of the ileocolic artery, which was successfully treated by embolization. She was discharged after an 18 day hospital stay. This case highlights a pseudoaneurysm caused by diverticulitis.

Endogenous Microbacteria Can Contribute to Ovarian Carcinogenesis by Reducing Iron Concentration in Cysts: A Pilot Study.

Among epithelial ovarian cancer, clear cell carcinoma is common for chemo-resistance and high mortality. This cancer arises from benign ovarian endometrioma (OE), which is a high oxidative stress environment due to the cystic retention of menstrual blood produced during menstruation and the "iron" liberated from the cyst. There has been strong evidence that the iron concentration in OE decreases when they become cancerous. A decrease in iron concentration is a necessary condition for the formation of cancer. However, the mechanism of carcinogenesis is not yet clear. In the current study, the bacterial flora in endometriosis-associated ovarian cancer (EAOC), including clear cell carcinoma, and their origin, OE, were investigated using next-generation sequencing. The Shannon index in the genus level was significantly higher in EAOC than in OE fluids. Among several bacterial flora that were more abundant than benign chocolate cysts, a number of bacterial species that correlate very well with iron concentrations in the cysts were identified. These bacterial species are likely to be associated with decreased iron concentrations and cancer development.

5-Aminosalicylic Acid-Induced Liver Injury in a Patient with Ulcerative Colitis: A Case Report.

Introduction: Drug-induced liver injury (DILI) associated with 5-aminosalicylic acid (5-ASA) is a rare but potentially life-threatening adverse event. Case Presentation: We report the case of a 58-year-old woman with ulcerative colitis who developed DILI after initiating maintenance therapy with the multimatrix system 5-ASA. The patient presented with grade 4 liver enzyme elevation on day 98 after initiating 5-ASA and was admitted to the hospital. Blood tests revealed the mixed liver injury, and imaging studies showed no abnormalities except for mild lymph node enlargement. Liver biopsy revealed acute lobular hepatitis with interfacial activity. The patient's score on the International Autoimmune Hepatitis Group 1999 revised scoring system was a total score of 10, causing a suspicion for the diagnosis of autoimmune hepatitis. The DDW-J 2004 scale calculated a total score of six, indicating a high probability of DILI. We suspected DILI due to 5-ASA, and the 5-ASA formulations were discontinued. The patient was treated with ursodeoxycholic acid and neominophagen C, and her liver function gradually improved without steroid treatment. Finally, we definitively diagnosed DILI based on the pathological findings and clinical course after discontinuation of 5-ASA. Conclusion: This case highlights the importance of monitoring liver function in patients receiving 5-ASA therapy.

Overexpression of MicroRNA-138 Affects the Proliferation and Invasion of Urothelial Carcinoma Cells by Suppressing SOX9 Expression.

SRY-box transcription factor 9 (SOX9) is important for sexual differentiation, chondrogenic differentiation, and cell proliferation in cancer. It acts as a target molecule of microRNA (miR)-138 in various tumors and is associated with tumor development and growth. In this study, we analyzed the functions of miR-138 and SOX9 in urothelial carcinoma. SOX9 was highly expressed in invasive urothelial carcinoma tissues. miR-138 precursor transfection of T24 and UMUC2 cells significantly decreased SOX9 expression, indicating that SOX9 is a miR-138 target in urothelial carcinoma. Moreover, miR-138 precursor or SOX9 small interfering RNA (siRNA) transfection decreased the proliferation of urothelial carcinoma cell lines. To further confirm that miR-138-SOX9 signaling is involved in cell proliferation and invasion, urothelial carcinoma cells were transfected with the miR-138 precursor or SOX9 siRNA. This transfection reduced the proliferation and invasion of cells via the promotion of autophagy and apoptosis and G0/G1 cell cycle arrest. These results suggest that miR-138-SOX9 signaling modulates the growth and invasive potential of urothelial carcinoma cells.