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BACKGROUND AND AIMS: No endoscopic scoring system has been established for immune-mediated colitis (IMC). This study aimed to establish such a system for IMC and explore its utility in guiding future selective immunosuppressive therapy (SIT) use compared to clinical symptoms. METHODS: This retrospective, international, 14-center study included 674 patients who developed IMC after immunotherapy and underwent endoscopic evaluation. Ten endoscopic features were selected by group consensus and assigned 1 point each to calculate an IMC endoscopic score (IMCES). IMCES cutoffs were chosen to maximize specificity for SIT use. This specificity was compared between IMCESs, and clinical symptoms were graded according to a standardized instrument. RESULTS: A total of 309 (45.8%) patients received SIT. IMCES specificity for SIT use was 82.8% with a cutoff of 4. The inclusion of ulceration as a mandatory criterion resulted in higher specificity (85.0% for a cutoff of 4). In comparison, the specificity of a Mayo endoscopic subscore of 3 was 74.6%, and the specificity of clinical symptom grading was much lower at 27.4% and 12.3%, respectively. Early endoscopy was associated with timely SIT use (P < .001; r = 0.4084). CONCLUSIONS: This is the largest multicenter study to devise an endoscopic scoring system to guide IMC management. An IMCES cutoff of 4 has a higher specificity for SIT use than clinical symptoms, supporting early endoscopic evaluation for IMC.
Subject(s)
Colitis , Colonoscopy , Severity of Illness Index , Humans , Retrospective Studies , Male , Female , Middle Aged , Adult , Colitis/pathology , Colonoscopy/methods , Immunosuppressive Agents/therapeutic use , Aged , Immunotherapy/methods , Sensitivity and Specificity , Ulcer/pathologyABSTRACT
It is of great value to develop general, low-cost and even household methods for colorectal cancer detection. Here, a portable detection strategy based on a personal glucose meter (PGM) was designed for meeting this purpose. In this strategy, the anti-EpCAM coated magnet beads (MBs) were used as capture probes for enriching cancer cells and the aptamer modified and invertase loaded graphene oxides (GO) were used as report probes for producing glucose signal. This method is sensitive with detection limit as low as 560â¯cells, and demonstrates excellent detection specificity. Meanwhile, we succeeded in the specific detection of target cells in 20% human serum samples, indicating this method has great prospect in clinical diagnosis. Moreover, this method presents favourable universality for detecting different colorectal cancer cells by just using different recognition aptamers. Importantly, this method can be implemented for the target cell detection at room temperature without any expensive and large-scale instruments but a portable PGM. Therefore, this portable detection method possesses great potential in point-of-care detection of colorectal cancer cells.
Subject(s)
Biosensing Techniques/methods , Colonic Neoplasms/diagnosis , Colorectal Neoplasms/diagnosis , Aptamers, Nucleotide , Cell Line , Humans , Point-of-Care TestingABSTRACT
Background: Immune checkpoint inhibitors (ICIs) have demonstrated effectiveness in treating many malignancies. Gastrointestinal (GI) adverse events are commonly reported; however, few reports describe upper GI tract toxic effects. We aimed to describe clinical features of upper GI injury related to ICI. Methods: We studied consecutive patients who received ICIs between April 2011 and March 2018 and developed upper GI symptoms requiring esophagogastroduodenoscopy (EGD). Results: Sixty patients developed upper GI symptoms between ICI initiation and 6 months after the last infusion. Among patients who had both EGD and colonoscopy (n = 38), 21 had endoscopic evidence of inflammation involving both the upper and lower GI tract. Overall, histological signs of inflammation of the stomach were evident in 83% of patients, but inflammation of the duodenum in 38%. Total of 42 patients had other risk factors of gastritis, i.e., chemotherapy, radiotherapy, and non-steroidal anti-inflammatory drugs. Only isolated gastric inflammation was seen on endoscopy in patients without these risk factors. The rates of ulceration were similar in the cohorts with and without other risk factors for gastritis. Isolated upper GI inflammation was related to anti-PD-1/L1 in 47% of patients. Immunosuppressive therapy in our cohort with upper GI toxicity consisted of steroids (42%) and infliximab or vedolizumab (23%). Most isolated upper GI symptoms were treated with proton pump inhibitors (65%) or H2 blockers (35%). Conclusion: We observed a correlation between ICI use and onset of upper GI inflammation even when other risk factors were excluded. Gastric involvement was evident more often than duodenal involvement on endoscopic and histological level.
Subject(s)
Antineoplastic Agents, Immunological/adverse effects , Gastroenteritis/chemically induced , Ulcer/chemically induced , Upper Gastrointestinal Tract/physiopathology , Aged , Endoscopy, Digestive System , Female , Gastroenteritis/pathology , Humans , Male , Middle Aged , Retrospective Studies , Ulcer/pathologyABSTRACT
The feasibility of using a polymerase chain reaction (PCR)-based label-free DNA sensor for the detection of Helicobacter pylori is investigated. In particular, H. pylori ureC gene, a specific H. pylori nucleic acid sequence, was selected as the target sequence. In the presence of ureC gene, the target DNA could be amplified to dsDNA with much higher detectable levels. After added the SYBR green I (SGI), the sensing system could show high fluorescence. Thus, the target DNA can be detected by monitoring the change of fluorescence intensity of sensing system. The clinical performance of this method was determined by comparing it with another conventional technique urea breath test (UBT). The result also showed good distinguishing ability between negative and positive patient, which was in good agreement with that obtained by the UBT. It suggests that the label-free fluorescence-based method is more suitable for infection confirmation test of H. pylori. This approach offers great potential for simple, sensitive and cost-effective identification of H. pylori infection.
Subject(s)
Genes, Bacterial , Helicobacter Infections/diagnosis , Helicobacter pylori/genetics , Spectrometry, Fluorescence/methods , Benzothiazoles , Breath Tests , DNA/analysis , DNA/genetics , Diamines , Fluorescent Dyes , Helicobacter Infections/microbiology , Helicobacter pylori/pathogenicity , Humans , Organic Chemicals , Polymerase Chain Reaction , Quinolines , Sensitivity and SpecificityABSTRACT
Background: Thyroid cancer, a leading type of endocrine cancer, accounts for 3-4% of all cancer diagnoses. This study aims to analyse and compare thyroid cancer patterns in China and the Group twenty (G20) countries, and predict these trend for the upcoming two decades. Methods: This observational longitudinal study utilised data from the Global Burden of Disease (GBD) study 2019. We used metrics including incidence, mortality, mortality-incidence ratio (MIR), age-standardised rate (ASR) and average annual percent change (AAPC) to examine thyroid cancer trends. Joinpoint regression analysis was used to identify periods manifesting notable changes. The association between sociodemographic index (SDI) and AAPC were investigated. The autoregressive integrated moving average (ARIMA) model was used to predict thyroid cancer trends from 2020 to 2040. Results: From 1990 to 2019, thyroid cancer incidence cases in China increased by 289.6%, with a higher AAPC of age-standardised incidence rate (ASIR) in men. Contrastingly, the G20 demonstrated a smaller increase, particularly among women over 50. Despite the overall age-standardised mortality rate (ASMR) was higher in the G20, the increase in mortality was less pronounced than in China. Age-standardised incidence rate increased across all age groups and genders, with a notable rise among men aged 15-49. ASMR decreased in specific age groups and genders, especially among women. Conversely, the ASMR significantly increased in group aged over 70. The MIR exhibited a declining trend, but this decrease was less noticeable in men and the group aged over 70. Joinpoint analysis pinpointed significant shifts in overall ASIR and ASMR, with the most pronounced increase in ASIR during 2003-2011 in China and 2003-2010 in the G20. Predictions suggested a continual ASIR uptrend, especially in the 50-69 age group, coupled with a predicted ASMR downturn among the elderly by 2040. Moreover, the proportion of thyroid cancer deaths attributable to high body mass index (BMI) escalated, with significant increase in Saudi Arabia and a rise to 7.4% in China in 2019. Conclusions: Thyroid cancer cases in incidence and mortality are escalating in both China and the G20. The increasing trend may be attributed to factors beyond overdiagnosis, including environmental and genetic factors. These findings emphasise the necessity for augmenting prevention, control, and treatment strategies. They also highlight the significance of international collaboration in addressing the global challenge posed by thyroid cancer.
Subject(s)
Thyroid Neoplasms , Humans , China/epidemiology , Male , Thyroid Neoplasms/epidemiology , Thyroid Neoplasms/mortality , Female , Middle Aged , Adult , Incidence , Aged , Longitudinal Studies , Global Health/statistics & numerical data , Adolescent , Young Adult , Forecasting , Global Burden of Disease/trendsABSTRACT
BACKGROUND: RICAP is a recognized adverse effect of radiation therapy (RT) that can adversely affect cancer patients' quality of life. Data on the clinical characteristics and outcomes of RICAP are scarce. We aimed to analyze the clinical and endoscopic characteristics of acute or chronic radiation-induced colitis and proctopathy (ARICAP and CRICAP) based on symptom onset after RT (≤ or >45 days, respectively). METHODS: This is a retrospective observational study of a single tertiary cancer center, from January 2010 and December 2018, of cancer patients with endoscopically confirmed ARICAP and CRICAP. We conducted univariate and multivariate logistic regression analyses to associate clinical variables with endoscopic and medical outcomes. RESULTS: One hundred and twelve patients were included (84% Caucasian; 55% female; median age of 59 years); 46% had ARICAP with non-bloody diarrhea as the predominant symptom, whereas 55% had CRICAP with mostly bloody diarrhea. Neovascularization was the most frequent finding on endoscopy, followed by bleeding. ARICAP patients more often received medical management (p < 0.001), whereas CRICAP patients with bleeding more often received argon plasma coagulation (APC) (p = 0.002). Female sex and undergoing less-intense RT treatments were more associated with medical treatment; bleeding clinically and during the endoscopy was more associated with APC treatment. However, APC treatment did not significantly reduce bleeding recurrence or RICAP symptoms. CONCLUSION: Patients with ARICAP and CRICAP experience different symptoms. Medical management should be considered before endoscopic therapy. APC may be useful in patients with endoscopically apparent bleeding.
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Aim: Our study aimed at investigating how LINC01133 functions in gastric cancer (GC) progression. Materials & methods: Gain-of-function and loss-of-function approaches were applied to analyze the effects of LINC01133, microRNA-576-5p (miR-576-5p) and somatostatin (SST) on the biological behaviors of GC cells and in tumor-bearing nude mice. Results: GC tissues and cells showed low expression of LINC01133, and LINC01133 overexpression decreased malignant phenotypes of GC cells. Moreover, LINC01133 upregulated SST through binding to miR-576-5p. Overexpressing miR-576-5p or suppressing SST reversed the functions of LINC01133 in biological potentials of GC cells and tumor growth. Conclusion: LINC01133 overexpression may inhibit GC development by downregulation of miR-576-5p and upregulation of SST, which suggests new therapeutic targets for GC.
Subject(s)
MicroRNAs/genetics , RNA Interference , RNA, Long Noncoding/genetics , Somatostatin/biosynthesis , Stomach Neoplasms/genetics , Stomach Neoplasms/metabolism , Animals , Cell Line, Tumor , Databases, Genetic , Disease Models, Animal , Female , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Humans , Mice , Models, Biological , Somatostatin/genetics , Stomach Neoplasms/pathology , TranscriptomeABSTRACT
Due to the steadily rising morbidity and mortality, thyroid cancer remains the most commonly seen endocrine cancer. The present study attempted to investigate the mechanism from the perspective of long non-coding RNA (lncRNA) regulation. We identified 53 markedly increased lncRNAs in thyroid cancer samples according to TCGA data. Among them, high lncRNA DIO3OS expression was a risk factor for thyroid cancer patients' poorer overall survival. DIO3OS showed to be considerably increased within thyroid cancer tissue samples and cells. Knocking down DIO3OS within thyroid carcinoma cells suppressed cancer cell viability, the capacity of DNA synthesis, cell invasion, as well as cell migration; besides, proliferating markers, ki-67 and PCNA, were decreased by DIO3OS knockdown. Cancer bioinformatics analysis suggested that NF-κB2 might be related to DIO3OS function in thyroid cancer carcinogenesis. NF-κB2 was positively correlated with DIO3OS, and DIO3OS knockdown decreased NF-κB2 protein levels. Knocking down NF-κB2 within thyroid carcinoma cells suppressed cancer cell viability, the capacity of DNA synthesis, cell invasion, cell migration, and the protein levels of proliferating markers. Let-7d directly targeted DIO3OS and NF-κB2; DIO3OS knockdown upregulated let-7d expression. The overexpression of let-7d suppressed cancer cell viability, the capacity of DNA synthesis, cell invasion, cell migration, as well as the protein levels of proliferating markers. Let-7d inhibition remarkably attenuated the functions of DIO3OS knockdown in NF-κB2 expression and thyroid cancer cell phenotype. In conclusion, DIO3OS/let-7d/NF-κB2 axis regulates the viability, DNA synthesis capacity, invasion, and migration of thyroid cancer cells. The clinical application of this axis needs further in vivo and clinical investigation.
ABSTRACT
BACKGROUND: Data on gastrointestinal toxicities related antiangiogenesis cancer therapy is very limited. We aim to describe the clinical, endoscopic, and histologic features and outcomes of antiangiogenesis-associated colitis and diarrhea (ACD) at a tertiary-care cancer center. PATIENTS AND METHODS: We performed a retrospective study of cancer patients who received antiangiogenesis therapy (AAT) and underwent endoscopy for ACD symptoms during 2000-2018. RESULTS: A total of 12,045 patients received AAT during the study period. Of these, 552 patients underwent lower gastrointestinal tract endoscopic evaluation after AAT. Among them, we identified 41 patients who developed ACD. The median time from AAT initiation to ACD onset was 20 weeks. Most patients received bevacizumab (83%). The median duration of ACD symptoms was 6 days. On endoscopy, 7 patients (17%) had mucosal ulceration, and 16 (39%) had nonulcerative inflammation. Active histologic inflammation was evident in 8 patients (20%). Thirteen patients (32%) received treatment for ACD: antibiotics in 5 (12%) and antimotility agents in 11 (27%). Sixteen patients (39%) were hospitalized for ACD, and 2 were admitted to the intensive care unit. One colonic perforation (2%) related to underlying malignancy was reported after colonoscopy. Patients with enterocolitis symptoms had more frequent abnormal endoscopic findings (P = .024) and less frequently received antimotility agents (P = .011) compared to those with diarrhea only. Abnormal endoscopic findings were associated with more hospitalizations (P = .063) compared to normal group. CONCLUSION: ACD is a rare adverse event of AAT and is usually mild. Despite its rarity, complications of ACD can be serious, requiring intensive care unit and surgery. Colonic perforation occurred after routine endoscopy after AAT in 2% of our cohort.
Subject(s)
Angiogenesis Inhibitors/adverse effects , Colitis/epidemiology , Diarrhea/epidemiology , Intestinal Perforation/epidemiology , Neoplasms/drug therapy , Aged , Biopsy , Colitis/chemically induced , Colitis/diagnosis , Colitis/immunology , Colon/diagnostic imaging , Colon/drug effects , Colon/immunology , Colon/pathology , Colonoscopy/statistics & numerical data , Diarrhea/chemically induced , Diarrhea/diagnosis , Diarrhea/immunology , Female , Humans , Intestinal Perforation/chemically induced , Intestinal Perforation/diagnosis , Intestinal Perforation/immunology , Male , Middle Aged , Retrospective Studies , Severity of Illness IndexABSTRACT
Background: Platinum-based therapy (PBT) can be limited by gastrointestinal adverse events, particularly PBT-related colitis and diarrhea (PCD). We studied clinical features, treatments, and outcomes of PCD. Methods: This was a retrospective study of cancer patients who received PBT and colonoscopic evaluation for PCD symptoms from 2009 to 2018. Results: Of 36,595 patients who received PBT, 86 (0.2%) met inclusion criteria. Median time from PBT initiation to PCD was 66 days. Regarding PBT type, 47% of the patients received carboplatin, 31% cisplatin, and 22% oxaliplatin. Median duration of PCD symptoms was 20 days. Colonoscopy revealed mucosal ulceration in 34% of the patients and nonulcerative inflammation in 33%. Half of the cohort needed hospitalization for PCD (49%). The majority received treatment for PCD (59%): immunosuppressive therapy in 21%, antibiotics in 27%, antimotility agents in 22%, and intravenous fluids in 51%. Eight patients (9%) were admitted to the intensive care unit for PCD management. Six patients (7%) experienced colonic perforation that required surgical intervention; two of them had gastrointestinal tumors. Physicians restarted PBT in 37 (43%) patients; 8 (22%) of them had PCD recurrence that was managed expectantly. Colonic perforation occurred more frequently with use of oxaliplatin and cisplatin than carboplatin (P=0.05). The median duration of PCD symptoms was longer in patients receiving carboplatin or cisplatin than in those receiving oxaliplatin (P=0.182). Conclusions: PCD is rare, but in a small subset of patients, it can lead to serious complications. Treatment of PCD is mainly supportive, but immunosuppressive therapy may be required.
ABSTRACT
BACKGROUND: Immune checkpoint inhibitor (ICI)-induced pancreatic injury (ICIPI) is not well documented in the literature. We aimed to describe the clinical characteristics and outcomes of patients who developed ICIPI. METHODS: We reviewed the medical records of consecutive patients who had a confirmed diagnosis of ICIPI (Common Terminology Criteria for Adverse Events grade ≥ 3 lipase elevation with or without clinical symptoms) from April 2011 through April 2018. RESULTS: Among the 2,279 patients received ICI and had lipase values checked thereafter, 82 (4%) developed ICIPI. Overall, 65% of patients received inhibitors of programmed death protein-1 or its ligand. Compared with asymptomatic presentation, patients who had clinical symptoms of pancreatitis (n = 32) had higher levels of lipase (P = 0.032), more frequent imaging evidence of pancreatitis (P = 0.055), and more frequent hospitalization (P < 0.001) and received intravenous fluids (P < 0.001) and steroids more frequently (P = 0.008). Twelve patients (15%) developed long-term adverse outcomes of ICIPI; three had chronic pancreatitis, four had recurrence of ICIPI, and six had subsequent diabetes. Among 35 patients who resumed ICI therapy, four (11%) had recurrence of lipase elevation. Logistic regression revealed that smoking and hyperlipidemia were associated with increased risk for long-term adverse outcomes of ICIPI, and intravenous fluids were associated with reduced risk. Patients who resumed ICI therapy survived longer than patients who discontinued ICI therapy permanently, statistically not significant (P = 0.0559). Patients who developed long-term adverse outcomes of ICIPI survived significantly longer than those who did not (P = 0.0295). The highest proportion of patients (6/21, 29%) developed long-term adverse outcomes of ICIPI was among those without typical symptoms of pancreatitis, continued ICI therapy after ICIPI, and did not receive intravenous fluids. CONCLUSION: ICIPI can present as typical acute pancreatitis, with risk of the development of a pseudocyst, diabetes, and chronic pancreatitis. ICI resumption after ICIPI may lead to recurrence of lipase elevation without increased risk of long-term adverse outcomes, and can increase survival duration. Intravenous fluids may prevent long-term adverse outcomes, but steroids do not appear to affect outcomes of ICIPI. Asymptomatic ICIPI presentation may lead to undertreatment of ICIPI owing to underestimation of its degree, and therefore, intravenous fluid administration could potentially could potentially be benificial to prevent long-term adverse outcomes even in asymptomatic patients.
Subject(s)
Antineoplastic Agents, Immunological/adverse effects , B7-H1 Antigen/antagonists & inhibitors , CTLA-4 Antigen/antagonists & inhibitors , Neoplasms/drug therapy , Pancreatitis/chemically induced , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Female , Humans , Lipase/blood , Male , Middle Aged , Neoplasms/blood , Pancreas/drug effects , Pancreas/pathology , Pancreatitis/blood , Pancreatitis/pathologyABSTRACT
BACKGROUND: Some studies have shown that malnutrition is associated with increased risk of mortality in older adults with cancer. However, evidence of its effect is limited and inconsistent. To assess the effect of malnutrition on overall survival in older adults with cancer, we performed a meta-analysis of available studies. METHODS: We systematically searched MEDLINE, EMBASE, Web of Science, CINAHL, and PsycINFO for observational studies that examined the association between malnutrition and risk of mortality in older adults with cancer (≥65â¯years). Malnutrition is defined according to assessment and screening tools in different studies. Older adults with malnutrition were compared with those with normal nutrition for overall survival. A random-effect model was fitted to estimate the summary relative risk (RR) and 95% confidence interval (CI). Between-studies heterogeneity was measured with the I2 statistic. RESULTS: Ten studies met the inclusion criteria, and a total of 4692 older adults with cancer were included in the meta-analysis. Heterogeneity existed among the different studies (I2â¯=â¯73.7%, pâ¯<â¯0.01). Malnutrition was significantly positively associated with increased risk of all-cause mortality (RR: 1.73; 95% CI: 1.23-2.41) compared with those with good nutrition status. A sensitivity analysis of 2773 older adults with cancer on the malnutrition assessed by Mini Nutrition Assessment (MNA), found that malnutrition is still associated with higher risk for all-cause mortality (RRâ¯=â¯2.13, 95% CI: 1.34-3.39). CONCLUSION: Our meta-analysis of observational studies found a significant effect of malnutrition on overall survival in older adults with cancer.
Subject(s)
Malnutrition/mortality , Neoplasms/mortality , Aged , Aged, 80 and over , Case-Control Studies , Female , Geriatrics/methods , Humans , Male , Malnutrition/diagnosis , Malnutrition/therapy , Medical Oncology/methods , Nutrition Assessment , Nutritional Support/methods , Observational Studies as TopicABSTRACT
To explore the efficiency and safety of laparoscopic anus-conserving operation for ultralow rectal cancer, we retrospectively reviewed 236 patients with ultralow rectal cancer who underwent laparoscopic anus-conserving operation (experimental group, n = 124) or conventional open surgery (control group, n = 112). Operation-related indexes, pathological results of mesentery, incidence rates of postoperative complications, anus preservation rates, anal sphincter controllability after surgery, and survival rates of the first, second, and third years after operation were compared between the two groups. The amount of intraoperative bleeding, first postoperative exhaust time, abdominal drainage, pain score, and hospital stay in the experimental group were significantly less than those in the control group (P < 0.05). There were no significant differences in the postoperative circumferential resection margin, distal resection margin, number of dissected lymph nodes, successful resection rate, and quality of mesorectum between the two groups (P > 0.05). The total incidence rate of postoperative complications, anal sphincter controllability, and survival rates after surgery were similar between the two groups (P > 0.05). The anus preservation rate of the experimental group (84.7%) was significantly higher than that of the control group (69.6%) (P < 0.05). Laparoscopic anus-conserving operation is effective and safe in treatment of patients with ultralow rectal cancer, which has advantages such as small trauma, less intraoperative bleeding, short hospital stay, rapid recovery, a low incidence rate of postoperative complications, and a high anus-preserving rate, so it is worthy of clinical application.
Subject(s)
Anal Canal/surgery , Laparoscopy , Postoperative Complications/epidemiology , Proctectomy/adverse effects , Rectal Neoplasms/pathology , Rectal Neoplasms/surgery , Aged , Female , Humans , Male , Middle Aged , Proctectomy/methods , Rectal Neoplasms/mortality , Retrospective Studies , Survival Rate , Treatment OutcomeABSTRACT
BACKGROUND: The gut microbiome impacts the efficacy of immune checkpoint inhibitor (ICI) therapy and the development of ICI-mediated diarrhea and/or colitis (IMDC). Antibiotic therapy,especially that with anaerobic activity, has profound effects on the gut microbiome. Therefore, we sought to assess the effect of antibiotics on the development of IMDC. METHODS: Patients who received ICI therapy from January 2016 to January 2018 were examined retrospectively. A Cox regression model was used to assess factors associated with overall survival. RESULTS: A total of 826 patients were included. Of these patients, 51.6% received inhibitors of programmed cell death protein-1 or its ligand, 32.0% received inhibitors of cytotoxic T-lymphocyte-associated antigen-4, and 16.5% received a combination of the two. IMDC occurred in 52.5% of the patients after a median of 8 weeks. Overall, 569 patients (68.9%) received antibiotic therapy. Antibiotic use at any time was associated with reduced IMDC occurrence and recurrence rates but also with frequent hospitalization and intensive care unit admission for IMDC as well as increased IMDC severity. Compared with patients who received antibiotic therapy only before ICI therapy initiation, those receiving it after ICI had a higher IMDC rate and more often needed immunosuppressive therapy and hospitalization for IMDC. Antibiotics with anaerobic activity were included in 51% of the antibiotic therapy regimens and were associated with increased immunosuppressant use, hospitalization, intensive care unit admission for IMDC, and severe IMDC grades. Forty-one patients received empiric prophylactic antibiotic therapy at IMDC onset. These patients more often needed immunosuppressive therapy, intravenous steroids, and infliximab/vedolizumab; had more frequent and longer hospitalization for IMDC and higher IMDC grades; and more frequently had IMDC recurrence than did patients who did not receive antibiotic therapy at the time of IMDC symptom onset. CONCLUSIONS: Whereas antibiotic therapy appeared to be protective against IMDC onset, use of antibiotics, especially those with anaerobic activity, after ICI therapy was associated with increased risk of severe IMDC.
Subject(s)
Anti-Bacterial Agents/therapeutic use , Antineoplastic Agents, Immunological/adverse effects , Colitis/drug therapy , Diarrhea/drug therapy , Neoplasm Recurrence, Local/drug therapy , Neoplasms/drug therapy , Aged , Biomarkers, Tumor/antagonists & inhibitors , Biomarkers, Tumor/immunology , CTLA-4 Antigen/antagonists & inhibitors , Colitis/chemically induced , Colitis/pathology , Diarrhea/chemically induced , Diarrhea/pathology , Female , Follow-Up Studies , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/immunology , Neoplasm Recurrence, Local/pathology , Neoplasms/immunology , Neoplasms/pathology , Prognosis , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Retrospective Studies , Survival RateABSTRACT
Following publication of the original article [1], the authors have reported that an author's name has been incorrectly spelled: the correct given name is Anne-Marie (instead of Anne-Maria P) and family name is Chaftari.
ABSTRACT
BACKGROUND: Chimeric antigen receptor T-cell (CART) therapy can significantly improve outcomes for patients with certain hematologic malignancies. The most notable drawbacks of CART are cytokine release syndrome and CART-related encephalopathy syndrome. Gastrointestinal adverse events (GI-AEs) have not yet been reported in association with CART. Herein, we describe the incidence and clinical features of GI-AEs observed after CART. MATERIALS AND METHODS: We report a case series of patients with hematologic malignancies who received CART, in a clinical trial or as the standard of care, and subsequently suffered from GI-AEs between 2012 and 2018. RESULTS: In our cohort, 37 of 132 (28%) patients experienced GI-AEs. All 37 experienced diarrhea with a median onset of 7 days (interquartile range, 4 to 25 d) after CART infusion. The median age of these patients was 58 years. Most had diffuse large B-cell lymphoma (51%). Seventeen patients experienced cytokine release syndrome, and 9 experienced CART-related encephalopathy syndrome. The interleukin-6 antagonist was required in 15 patients. Overall, 49% of patients had grade 1 diarrhea, 32% had grade 2, and 15% had grade 3. Other gastrointestinal symptoms in these patients were abdominal pain (41%), nausea and vomiting (49%), fever (8%), bloody stools (3%), and abdominal distension (5%). The median duration of symptoms was 6 days (interquartile range, 3 to 9 d). In 32 patients who underwent imaging, 8 (25%) had findings suggestive of gastrointestinal tract inflammation. Nine (24%) patients experienced GI-AE recurrence after initial improvement. The symptoms were attributed to an alternative cause in 17 (13%) cases and to CART in 20 (15%) cases. One patient developed CART-related refractory colitis that eventually responded to antibiotics for pneumonia. CONCLUSION: CART-related GI-AEs occur in 15% of patients treated with CART. These symptoms are typically mild and self-limiting, requiring only symptomatic treatment. Nevertheless, CART may, in rare cases, lead to refractory colitis.
Subject(s)
Gastrointestinal Diseases/chemically induced , Gastrointestinal Diseases/epidemiology , Hematologic Neoplasms/drug therapy , Immunotherapy, Adoptive/adverse effects , Receptors, Chimeric Antigen/administration & dosage , Adult , Age Distribution , Antineoplastic Combined Chemotherapy Protocols , Asparaginase , Biopsy, Needle , Cohort Studies , Cytarabine , Daunorubicin , Female , Gastric Mucosa/drug effects , Gastric Mucosa/pathology , Gastritis/chemically induced , Gastritis/pathology , Gastrointestinal Diseases/physiopathology , Hematologic Neoplasms/pathology , Humans , Immunohistochemistry , Immunotherapy, Adoptive/methods , Incidence , Male , Middle Aged , Prognosis , Retrospective Studies , Risk Assessment , Severity of Illness Index , Sex Distribution , ThioguanineABSTRACT
AIM: To compare the results of total laparoscopic distal gastrectomy (TLDG) and laparoscopy-assistedâ¯distal gastrectomy (LADG) and explore the safety and feasibility of TLDG. METHODS: Data were collected and analyzed from patients underwent TLDG and LADG from January 2009 to December 2011â¯at our institution. RESULTS: 127 LADG cases and 104 TLDG cases were included and balanced for age, sex, BMI, ASA scores, and CEA level in this study. A decrease in postoperative pain (Pâ¯<â¯0.001), wound infection rate (Pâ¯=â¯0.013), and hospitalization time after surgery (Pâ¯<â¯0.001) was found in the TLDG group. Compared with the LADG group, there was no increase in operative time (Pâ¯=â¯0.084), intraoperative blood loss (Pâ¯=â¯0.061), or anastomotic fistula rate (Pâ¯=â¯0.473). Statistical differences did not exist in recurrence and (or) metastasis (Pâ¯=â¯0.204), 5-years disease-free survival (DFS) rate and overall survival (OS) (Pâ¯=â¯0.570 and 0.560, respectively). CONCLUSION: As long as it follows the surgical principles of malignant tumor, TLDG can achieve the same therapeutic effect as LADG does. TLDG is safe and feasible for gastric cancer patients though further studies are needed.
Subject(s)
Gastrectomy/methods , Laparoscopy/methods , Stomach Neoplasms/surgery , China/epidemiology , Female , Follow-Up Studies , Hand-Assisted Laparoscopy/methods , Humans , Male , Middle Aged , Operative Time , Retrospective Studies , Stomach Neoplasms/diagnosis , Stomach Neoplasms/mortality , Survival Rate/trends , Tomography, X-Ray Computed , Treatment OutcomeABSTRACT
Long noncoding RNA serves important roles in gastric cancer (GC). However, the prognostic significance and tumorigenesis effect of AFAP1-antisense RNA 1 (AS1) in GC remain to be clarified. The present study was conducted in order to determine the expression level of AFAP1-AS1 by reverse transcription-quantitative polymerase chain reaction. It was demonstrated that AFAP1-AS1 expression level was higher in GC tissues in comparison with adjacent tissues. By analyzing 66 GC tissue specimens, AFAP1-AS1 expression level was found to be markedly associated with tumor size, clinical stage and differentiation. By performing multivariate Cox regression test, AFAP1-AS1 expression level was confirmed to be an independent factor for poor prognosis in patients with GC. Furthermore, SGC-7901 and BGC-823 cells were used for further investigation following transfection of an AFAP1-AS1 short hairpin RNA lentiviral vector. Knockdown of AFAP1-AS1 significantly inhibited GC cell proliferation, migration and invasion abilities in vitro. Finally, nude mice experiments confirmed that downregulation of AFAP1-AS1 in GC cells suppressed tumor growth in vivo. In conclusion, the results of the present study suggested that AFAP1-AS1 may serve as a valuable prognostic indicator and therapeutic target for GC.