Cytokine Release Syndrome-Associated Colitis: Insights From a Case of Rituximab-Induced Pancolitis.

Rituximab (RTX), a widely used monoclonal antibody for hematologic malignancies and rheumatologic disorders, is known for infusion-related reactions. However, its potential to induce colitis is often overlooked. We present an 85-year-old woman with chronic lymphocytic leukemia experiencing severe adverse effects during her fourth RTX infusion, including abdominal pain, hypotension, and bright red blood per rectum. Computed tomography of the abdomen and pelvis with contrast revealed pancolonic mural wall thickening without perforation. Prompt treatment with vasopressors and intravenous fluids led to symptom resolution within 24 hours. We highlighted the importance of recognizing RTX-induced colitis and discussed and depicted immunological dysregulation mechanisms involved.

Rare Case of Pediatric Post-transplant Lymphoproliferative Disorder Presenting With Pleural Masses Complicated by Pleural Effusions.

Post-transplant lymphoproliferative disorder is a complication in organ transplant recipients characterized by uncontrolled proliferation of B-lymphocytes, occurring in 6% of pediatric patients, with risk factors including primary Epstein-Barr virus infection, intensity of immunosuppression, and cytomegalovirus infection. The clinical symptoms are often nonspecific, and it is associated with a high mortality rate if left untreated. We describe a rare case of post-transplant lymphoproliferative disorder who presented with pleural-based masses resulting in pleural effusions.

A strategy to improve the solubility and bioavailability of the insoluble drug piperlongumine through albumin nanoparticles.

Piperlongumine (PL) is a biologically active alkaloid derived from peppers, has significant cytotoxic effects on cancer with no cytotoxicity. This study used NabTM technology to prepare PL albumin nanoparticles (PL-BSA-NPs) to improve water solubility and bioavailability. We carried out a pharmacological evaluation of the PL-BSA-NPs. The morphological profile of the PL-BSA-NPs was relatively uniform, with an average particle size of approximately 210 nm, with drug load of 2.1% and encapsulation rate of 87.6%. PL-BSA-NPs were stable for 4 weeks when stored at 4°C. In vitro release behavior of the PL-BSA-NPs showed a sustained release, with a cumulative release of 67.24% in approximately 24 hours. The pharmacokinetic properties of PL-BSA-NPs were shown that PL-BSA-NPs could maintain a certain level of blood drug concentration for a long time, thus demonstrating the sustained release and increased bioavailability of PL. Finally, we investigated the in vitro antitumor activity of the PL-BSA-NPs and found that PL can significantly inhibit HepG2 cell proliferation, and that PL-BSA-NPs enhanced the inhibitory effect of PL on this proliferative effect. Thus, we concluded that PL can destroy liver cancer cells by increasing ROS levels. These results suggested that PL-BSA-NPs show promising potential as a targeted anti-tumor drug.

Idiopathic myointimal hyperplasia of the mesenteric veins: A systematic review and individual patient data regression analysis.

BACKGROUND AND AIM: Idiopathic myointimal hyperplasia of the mesenteric veins (IMHMV) is an uncommon cause of colonic ischemia for which surgical treatment is typically curative. We describe clinical, radiologic, and endoscopic findings in IMHMV patients to provide clinicians with a framework for pre-surgical identification of this rare disease. METHODS: We performed a systematic review of seven databases for IMHMV cases and identified additional cases from Yale New Haven Hospital records. To identify features specifically associated with colonic ischemia due to IMHMV, we performed multivariate logistic regression analysis incorporating data from a large cohort of patients with biopsy-proven ischemic colitis. RESULTS: A total of 124 patients with IMHMV were identified (80% male, mean age 53 years, 56% Caucasian). Presenting symptoms were most commonly abdominal pain (86%) and diarrhea (68%). The most affected areas were the sigmoid colon (91%) and rectum (61%). Complications associated with diagnostic delay occurred in 29% of patients. Radiologic vascular abnormalities including non-opacification of the inferior mesenteric vein were observed in 35% of patients. Of the patients, 97% underwent curative surgical resection. Compared with non-IMHMV colonic ischemia, IMHMV was significantly associated with younger age, male sex, absence of rectal bleeding on presentation, rectal involvement, and mucosal ulcerations on endoscopy. CONCLUSION: IMHMV is a rare, underreported cause of colonic ischemia that predominantly involves the rectosigmoid. Our findings suggest younger age, rectal involvement, and absence of rectal bleeding as clinical features to help identify select patients presenting with colonic ischemia as having higher likelihood of IMHMV and therefore consideration of upfront surgical management.

Management of Patients With Acute Lower Gastrointestinal Bleeding: An Updated ACG Guideline.

Acute lower gastrointestinal bleeding (LGIB) is a common reason for hospitalization in the United States and is associated with significant utilization of hospital resources, as well as considerable morbidity and mortality. These revised guidelines implement the Grading of Recommendations, Assessment, Development, and Evaluation methodology to propose recommendations for the use of risk stratification tools, thresholds for red blood cell transfusion, reversal agents for patients on anticoagulants, diagnostic testing including colonoscopy and computed tomography angiography (CTA), endoscopic therapeutic options, and management of antithrombotic medications after hospital discharge. Important changes since the previous iteration of this guideline include recommendations for the use of risk stratification tools to identify patients with LGIB at low risk of a hospital-based intervention, the role for reversal agents in patients with life-threatening LGIB on vitamin K antagonists and direct oral anticoagulants, the increasing role for CTA in patients with severe LGIB, and the management of patients who have a positive CTA. We recommend that most patients requiring inpatient colonoscopy undergo a nonurgent colonoscopy because performing an urgent colonoscopy within 24 hours of presentation has not been shown to improve important clinical outcomes such as rebleeding. Finally, we provide updated recommendations regarding resumption of antiplatelet and anticoagulant medications after cessation of LGIB.

Two Cases of Biphasic Synovial Sarcoma With Expression of PAX8 and ER: A Diagnostic Pitfall.

Synovial sarcoma (SS) is a high-grade malignant neoplasm frequently arising in the deep soft tissue of the lower and upper extremities of young adults. Primary SS in the pelvis is extremely rare with scattered case reports. It often causes a diagnostic challenge in small biopsy and/or with aberrant expression of immunohistochemical markers. Here, we report 2 unusual cases of SS in the pelvis. Microscopically both cases present with biphasic morphology including spindle and epithelioid cells. In addition, the tumor cells in both cases expressed PAX8 and estrogen receptor. PAX8 is a transcription factor usually expressed in tumors of thyroid gland, kidney, and Müllerian system origin. The expression of PAX8 especially with co-expression of estrogen receptor can be misleading and result in a diagnosis of Müllerian tumors in female patients with pelvic masses. The diagnosis of SS for both cases was confirmed either with the fluorescence in situ hybridization or reverse transcription polymerase chain reaction showing a SS18 (SYT) (18q11) gene rearrangement. It is imperative to include SS in the differential diagnosis for malignant neoplasms exhibiting monotonous spindle cells (monophasic SS) and biphasic mixed monotonous spindle and epithelioid tumor cells in female patients with a pelvic mass. Molecular study for SS18 translocation is essential for the diagnosis in such cases.

Colonoscopy after a Positive Stool-based Test for Colon Cancer Screening: Moving Toward a Better Understanding of What to Expect.

Stool-based tests for colorectal cancer, including fecal immunochemical testing (FIT) and multitarget stool DNA testing (mt-sDNA), are among the recommended first-line screening options for patients at average risk for colorectal cancer and offer advantages over colonoscopy. However, stool-based tests have high false-positive rates, and the expected yield of colonoscopy after positive FIT compared with positive mt-sDNA is not well studied. As discussed in this issue of Cancer Prevention Research, the presence of a precancerous lesion in the majority of cases with either positive stool-based test is expected. In addition, a positive mt-sDNA is associated with a higher risk for finding any neoplasia on colonoscopy compared with positive FIT, and particularly associated with higher prevalence of clinically relevant serrated polyps compared with positive FIT. Further research is needed on what to expect from positive stool-based testing on average risk 45-49 years old patients, the newest cohort indicated for colorectal cancer screening. See related article, p. 455.

Validation of the Adapted Clavien-Dindo in Trauma (ACDiT) Classifications in Medical and Surgical Management of Acute Diverticulitis.

OBJECTIVES: To validate the adapted Clavien-Dindo in trauma (ACDiT) tool as a novel outcome measure for patients with acute diverticulitis managed both operatively and nonoperatively. BACKGROUND: Complications following diverticulitis are difficult to classify because no traditional tools address patients managed both operatively and nonoperatively. The ACDiT grading system-graded from 0 to 5b-is applied in this manner but has not yet been validated for this patient group. METHODS: We performed a 5-year observational study of patients with acute diverticulitis at a safety-net hospital. Baseline demographics and hospitalization data were collected. ACDiT scores were assigned, and validation was undertaken by comparing scores with hospital-free days, and verifying that higher scores were associated with known risk factors for poor outcomes. Inverse probability weighted propensity scores were assigned for surgical management, and inverse probability weighted regression analysis was used to determine factors associated with ACDiT ≥ grade 2. RESULTS: Of 260 patients, 188 (72%) were managed nonoperatively. Eighty (31%) developed a complication; 73 (91%) were grades 1 to 3b. Higher grades correlated inversely with hospital-free days (rs = -0.67, P < 0.0001) for all patients and for nonoperative (rs = -0.63, P < 0.0001) and operative (rs = -0.62, P < 0.0001) patients. Hinchey 2 to 3 and initial operative management had higher odds of having a complication of ACDiT ≥ grade 2. CONCLUSION: The ACDiT tool was successfully applied to acute diverticulitis patients managed operatively and nonoperatively, is associated with known risk factors for adverse outcomes. ACDiT may be considered a meaningful outcome measure for comparing strategies for acute diverticulitis.

Factors Associated With Emergency Department Discharge, Outcomes and Follow-Up Rates of Stable Patients With Lower Gastrointestinal Bleeding.

BACKGROUND: Lower gastrointestinal bleeding (LGIB) is a common reason for hospitalization. However, recent data suggest low-risk patients may be safely evaluated as an outpatient. Here, we compare stable LGIB patients discharged from the emergency department (ED) with those admitted, determine factors associated with discharge and 30-day outcomes, and evaluate follow-up rates amongst the discharged cohort. METHODS: A retrospective study of stable LGIB patients (heart rate < 100 beats/min, systolic blood pressure > 100 mm Hg and blood on rectal exam) who presented to the ED was conducted. Factors associated with discharge and rates of outpatient follow-up were determined in the discharged cohort. Therapeutic interventions and 30-day outcomes (including re-bleeding, re-admission and mortality rates) were compared between the admitted and discharged groups. RESULTS: Ninety-seven stable LGIB patients were reviewed, of whom 38% were discharged and characteristics associated with discharge included age (P < 0.001), lack of aspirin (P < 0.002) and anticoagulant (P < 0.004) use, higher index hemoglobin (P < 0.001) and albumin (P < 0.001), lower blood urea nitrogen (P < 0.001) and creatinine (P = 0.008), lower Oakland score (P < 0.001), lower Charlson Comorbidity Index (P < 0.001) and lack of transfusion requirements (P < 0.001). There was no statistical difference in 30-day re-bleeding, re-admission or mortality rates between admitted and discharged patients. Discharged patients had a 46% outpatient follow-up rate. CONCLUSIONS: While early discharge in low-risk LGIB patients appears to be safe and associated with a decrease in length of stay, further studies are needed to guide timely and appropriate outpatient evaluation.

Diverticulosis, Diverticulitis, and Diverticular Bleeding.

Diverticulosis is an anatomic change in the colon that is characterized by outpouching of the mucosa and submucosa through the muscularis. Its prevalence increases with age so most of the elderly patients have this condition. Although diverticulosis is common, diverticular disease, in which there are clinical sequelae, is rare. This collective term includes diverticulitis, diverticular hemorrhage and less well-defined entities such as segmental colitis associated with diverticulosis, and symptomatic uncomplicated diverticular disease. Diverticulitis presents as acute lower abdominal pain, and initial management traditionally includes antibiotics, with surgery reserved for complicated disease, although newer evidence questions the optimal role and timing of both interventions.

Progress and Future Trends in PET/CT and PET/MRI Molecular Imaging Approaches for Breast Cancer.

Breast cancer is a major disease with high morbidity and mortality in women worldwide. Increased use of imaging biomarkers has been shown to add more information with clinical utility in the detection and evaluation of breast cancer. To date, numerous studies related to PET-based imaging in breast cancer have been published. Here, we review available studies on the clinical utility of different PET-based molecular imaging methods in breast cancer diagnosis, staging, distant-metastasis detection, therapeutic and prognostic prediction, and evaluation of therapeutic responses. For primary breast cancer, PET/MRI performed similarly to MRI but better than PET/CT. PET/CT and PET/MRI both have higher sensitivity than MRI in the detection of axillary and extra-axillary nodal metastases. For distant metastases, PET/CT has better performance in the detection of lung metastasis, while PET/MRI performs better in the liver and bone. Additionally, PET/CT is superior in terms of monitoring local recurrence. The progress in novel radiotracers and PET radiomics presents opportunities to reclassify tumors by combining their fine anatomical features with molecular characteristics and develop a beneficial pathway from bench to bedside to predict the treatment response and prognosis of breast cancer. However, further investigation is still needed before application of these modalities in clinical practice. In conclusion, PET-based imaging is not suitable for early-stage breast cancer, but it adds value in identifying regional nodal disease and distant metastases as an adjuvant to standard diagnostic imaging. Recent advances in imaging techniques would further widen the comprehensive and convergent applications of PET approaches in the clinical management of breast cancer.

Gastrointestinal Bleeding in Patients With Coronavirus Disease 2019: A Matched Case-Control Study.

INTRODUCTION: Although current literature has addressed gastrointestinal presentations including nausea, vomiting, diarrhea, abnormal liver chemistries, and hyperlipasemia as possible coronavirus disease 2019 (COVID-19) manifestations, the risk and type of gastrointestinal bleeding (GIB) in this population is not well characterized. METHODS: This is a matched case-control (1:2) study with 41 cases of GIB (31 upper and 10 lower) in patients with COVID-19 and 82 matched controls of patients with COVID-19 without GIB. The primary objective was to characterize bleeding etiologies, and our secondary aim was to discuss outcomes and therapeutic approaches. RESULTS: There was no difference in the presenting symptoms of the cases and controls, and no difference in severity of COVID-19 manifestations (P > 0.05) was observed. Ten (32%) patients with upper GIB underwent esophagogastroduodenoscopy and 5 (50%) patients with lower GIBs underwent flexible sigmoidoscopy or colonoscopy. The most common upper and lower GIB etiologies were gastric or duodenal ulcers (80%) and rectal ulcers related to rectal tubes (60%), respectively. Four of the esophagogastroduodenoscopies resulted in therapeutic interventions, and the 3 patients with rectal ulcers were referred to colorectal surgery for rectal packing. Successful hemostasis was achieved in all 7 cases that required interventions. Transfusion requirements between patients who underwent endoscopic therapy and those who were conservatively managed were not significantly different. Anticoagulation and rectal tube usage trended toward being a risk factor for GIB, although it did not reach statistical significance. DISCUSSION: In COVID-19 patients with GIB, compared with matched controls of COVID-19 patients without GIB, there seemed to be no difference in initial presenting symptoms. Of those with upper and lower GIB, the most common etiology was peptic ulcer disease and rectal ulcers from rectal tubes, respectively. Conservative management seems to be a reasonable initial approach in managing these complex cases, but larger studies are needed to guide management.

Design, synthesis, and biological activity of a novel series of benzofuran derivatives against oestrogen receptor-dependent breast cancer cell lines.

A docking study of a novel series of benzofuran derivatives with ERα was conducted. In this study, we report the synthesis of a novel series of benzofuran derivatives and evaluation of their anticancer activity in vitro against MCF-7 human breast cancer cells, as well as their potential toxicity to ER-independent MDA-MB-231 breast cancer cells, human renal epithelial HEK-293 cells, and human immortal keratinocytes (HaCaT cells) by using the MTT colorimetric assay. The screening results indicated that the target compounds exhibited anti-breast cancer activity. The target compound 2-benzoyl-3-methyl-6-[2-(morpholin-4-yl)ethoxy]benzofuran hydrochloride (4e) exhibited excellent activity against anti-oestrogen receptor-dependent breast cancer cells and low toxicity. The preliminary structure-activity relationships of the target benzofuran derivatives have been summarised. In conclusion, the novel benzofuran scaffold may be a promising lead for the development of potential oestrogen receptor inhibitors.

Advances in Functional Imaging in the Assessment of Head and Neck Cancer.

This article discusses the application of fludeoxyglucose PET/computed tomography (CT) technology in head and neck cancer diagnosis and management, as well as advantages and disadvantages relative to traditional imaging modalities. A successful scan relies on precise patient preparation, and compliance to specific protocols before and during the scan. Finally, this article briefly introduces a PET/CT scan recently approved by the Food and Drug Administration for neuroendocrine tumors.

Takotsubo cardiomyopathy after an upper and lower endoscopy: a case report and review of the literature.

BACKGROUND: Gastrointestinal endoscopies are safe and follow guidelines that emphasize patient care. Although adverse outcomes are rare, high-risk patients may be predisposed to certain events. CASE PRESENTATION: We report a unique case of a Caucasian woman with takotsubo cardiomyopathy following an upper and lower endoscopy. CONCLUSIONS: Our report suggests the importance of understanding possible endoscopic complications in patients who may experience stress cardiomyopathy.

Hiatal Hernia Presenting with Recurrent Non-ST Elevation Myocardial Infarction and Cardiac Tamponade.

Hiatal hernia is a common pathology, particularly among the elderly or obese populations. Occasionally, markedly dilated hernias can impinge on surrounding structures, notably the heart or lung. In such cases, morbidity can be considerable. We present a case of an enlarging hiatal hernia that compressed the heart, leading to recurrent non-ST elevation myocardial infarction with cardiac tamponade. The patient was successfully managed with nasogastric decompression and surgical repair. We recommend that extrapericardial pathology be considered in tamponade patients with concurrent hiatal hernia and that surgery should be considered the definitive treatment modality.

To Scope or Not to Scope? The Safety of Upper Endoscopy in the Setting of Pulmonary Embolism.

OBJECTIVES: We aimed to describe the frequency of upper endoscopy and associated outcomes in subjects hospitalized with upper GI bleeding (UGIB) and pulmonary embolism (PE). METHODS: We performed a cross-sectional study using the Nationwide Inpatient Sample from 2007 to 2014. The association between upper endoscopy and in-hospital mortality was evaluated using propensity score matching. RESULTS: A total of 44,412 subjects had a coexistent PE and UGIB. 63.5% had an inpatient upper endoscopy with a lower likelihood of in-hospital death and a shorter length of stay. CONCLUSIONS: A substantial proportion of inpatients with PE and UGIB undergo endoscopy with a relatively lowmortality rate.

Can bone scans guide therapy with radium-223 dichloride for prostate cancer bone metastases?

BACKGROUND: Radium-223 dichloride (Ra-223 Xofigo) has recently been approved as an addition to the host of available therapies in the USA as a treatment option for metastatic castrate-resistant prostate cancer (mCRPC) with bone metastases. This study describes our initial experience in patients treated with Ra-223 dichloride. It attempts to optimize patients' selection for the best outcome from Ra-223 dichloride therapy. METHODS: Consecutive patients who were referred for treatment with Ra-223 dichloride were prospectively followed. Patients' demographics, functional status per the Eastern Cooperative Oncology Group (ECOG) performance score, pain level per the numeric rating score (NRS), prostate-specific antigen (PSA), creatinine, and hematological values were compared at baseline and at the end of therapy. Patients also had a bone scan before starting therapy and at the end of therapy. Patients were divided into the favorable response (FR) group if their pain and/or functional status improved and the unfavorable response (UR) group if they did not improve, deteriorated, or deceased. Bone scan findings before and after Ra-223 dichloride therapy were compared in both the FR and UR groups. RESULTS: Twenty patients were treated with Ra-223 dichloride. Twelve patients had innumerable bone metastases, three patients had super scans, and three patients had two to seven bone lesions. Two patients were lost to follow-up after the first injection. There were eight patients in the FR group and 10 patients in the UR group. Patients with UR had mean ECOG and NRS pain scores of 1.3 and 5.0 versus 0.8 and 4.4 in the FR group. The mean PSA and creatinine levels in the UR group were 445.2 ng/mL and 1.2 mg/dL versus 22.7 ng/mL and 1.1 mg/dL in the FR group. The mean hemoglobin, platelets, and absolute neutrophil values were 11.2 g/dL, 314.9 K/cmm, and 7.3 K/cmm in the UR group versus 11.6 g/dL, 207.0 K/cmm, and 6.2 K/cmm in the FR group. Seven of the eight patients with FR had a bone scan at the end of therapy showing improvement in five patients, a mixed response in one patient, and progression in another patient. Five patients in the UR group completed five or six injections and had bone scans showing flare of bone metastases in three patients, progression in one patient, and improvement in the fifth patient. Three patients in the UR group died after the first or second injections. Two of these patients had baseline super scans and the third one had widespread bone metastases. CONCLUSION: mCRPC patients with lower PSA levels at baseline and fewer bone lesions are more likely to respond favorably to Ra-223 dichloride therapy.