Coronavirus disease 2019-associated thrombotic microangiopathy treated with plasma exchange and antihypertensive therapy in a patient with HIV: A case report with literature review.

RATIONALE: Coronavirus disease 2019 (COVID-19) is an infectious disease that often causes complications in multiple organs and thrombosis due to abnormal blood coagulation. This case report aimed to describe the clinical course of COVID-19-associated thrombotic microangiopathy (TMA) and reviewed the comprehensive information on TMA, thrombotic thrombocytopenic purpura (TTP), and atypical hemolytic uremic syndrome associated with COVID-19 in the past literature. PATIENT CONCERNS: A 46-year-old Japanese man was diagnosed with human immunodeficiency virus infection 10 years ago and treated with antiretroviral therapy. The patient presented with fever, malaise, hematuria, and bilateral upper abdominal discomfort for the past 4 days. DIAGNOSES: COVID-19-associated TMA was diagnosed based on a positive polymerase chain reaction for severe acute respiratory syndrome coronavirus 2 and laboratory findings such as thrombocytopenia, acute kidney injury, and hemolytic anemia. Malignant hypertension and human immunodeficiency virus infection were also considered as differential diagnoses of TMA. INTERVENTIONS: Considering the possibility of TTP, plasma exchange was performed, and glucocorticoids were administered. Hemodialysis was performed for acute kidney injury. Antihypertensive drugs were administered to control the high blood pressure. OUTCOMES: Platelet count and renal function improved, and hemodialysis was no longer required. The patient was in good general condition and was discharged from the hospital. LESSONS: COVID-19-associated TMA should be considered as a differential diagnosis during the COVID-19 epidemic. Excessive inflammation and severe COVID-19 are not essential for TMA development. Early intervention using conventional TMA treatments, such as plasma exchange and corticosteroids, might be important in improving prognosis while differentiating between TTP and atypical hemolytic uremic syndrome. Antihypertensive therapy may be helpful in the treatment of COVID-19-associated TMA.

Submucosal fat accumulation in human colorectal tissue and its association with abdominal obesity and insulin resistance.

BACKGROUND: In addition to visceral fat, peripheral ectopic fat accumulation is suggested to play a role in the pathophysiology of metabolic syndrome, which is known to be associated with not only cardiovascular diseases and type 2 diabetes mellitus but also colorectal cancer. OBJECTIVE: This study aims to clarify whether there is ectopic fat accumulation in human colorectal tissue in association with metabolic syndrome or its components such as abdominal obesity and insulin resistance. METHODS: Lipid contents of colorectal tissue were measured in 27 patients with colorectal polyp excised endoscopically. In addition, lipid droplets were immunohistochemically estimated using anti-perilipin antibody in 32 patients with colorectal cancer resected surgically. RESULTS: Increasing tissue triglyceride/phospholipid ratio was associated with increasing body mass index, fasting plasma insulin level and homeostasis model assessment as an index of insulin resistance (HOMA-IR), and also decreasing serum adiponectin level. Lipid droplets were observed in the submucosal region of colorectal tissue. The amount of lipid droplets was associated with increasing body mass index, waist circumference and visceral fat area. CONCLUSION: This study showed the presence of submucosal fat accumulation in human colorectal tissue and its association with abdominal obesity and insulin resistance.

A water-jet videoendoscope may reduce operation time of endoscopic submucosal dissection for early gastric cancer.

BACKGROUND: One of the problems with endoscopic submucosal dissection (ESD) for early gastric cancer is that it prolongs procedure time considerably. AIM: The purpose of this study was to investigate whether a videoendoscope with water-jet function shortened the time of ESD for early gastric cancer. METHODS: A total of 82 early gastric cancers that were intramucosal, differentiated-type adenocarcinoma ≤2 cm, without ulcer or scar, in 75 consecutive patients were investigated. Three supervised resident endoscopists participated as operators. After stratification by the operator and tumor location, the lesions were randomly assigned to the water-jet videoendoscope or a conventional videoendoscope groups. An insulated tipped knife was used for the ESD procedure. Total operation time was evaluated as a primary endpoint. RESULTS: The median (25-75th percentile) total operation time for the water-jet videoendoscope group was 51 (33-87) minutes, which was shorter than the 62 (43-88) minutes for the conventional videoendoscope, but it did not reach significance (P = 0.201). Multivariate analysis revealed that the water-jet videoendoscope (OR 3.0, P = 0.046), tumor size ≤14 mm (OR 3.2, P = 0.040) and antral tumor (OR 4.5, P = 0.046) were significantly associated with short (≤60 min) operation time. CONCLUSIONS: The water-jet videoendoscope may reduce operation time of ESD for early gastric cancer, compared with conventional videoendoscope. A large-scale multicenter trial is warranted to clarify the efficacy of the water-jet videoendoscope for gastric ESD.

Enzymatic synthesis of poly(α-ethyl ß-aspartate) by poly(ethylene glycol) modified poly(aspartate) hydrolase-1.

We recently discovered that poly(aspartate) (PAA) hydrolase-1 from Pedobacter sp. KP-2 has a unique property of specifically cleaving the amide bond between ß-aspartate units in thermally synthesized PAA (tPAA). In the present study, the enzymatic synthesis of poly(α-ethyl ß-aspartate) (ß-PAA) was performed by taking advantage of the substrate specificity of PAA hydrolase-1. No polymerization of diethyl L-aspartate by native PAA hydrolase-1 occurred because of the low dispersibility of the enzyme in organic solvent. Poly(ethylene glycol) (PEG) modification of the enzyme improved its dispersibility and enabled it to polymerize the monomer substrate. MALDI-TOF MS analysis showed that the synthesized polymer was observed in the range of m/z = 750-2 500. This analysis also revealed that the polymer was composed of ethyl aspartate units, containing either an ethyl ester or a free carboxyl end group at its carboxyl terminus. (1) H NMR analysis demonstrated that the synthesized polymer consisted of only ß-amide linkages. Thus, the present results indicate that PAA hydrolase-1 modified with PEG is useful for the synthesis of ß-PAA due to its unique substrate specificity and good dispersibility in organic solvent.

Scraping cytology with a guidewire for pancreatic-ductal strictures.

BACKGROUND: Strictures of the pancreatic duct may be caused by a variety of underlying pathologic conditions that imaging examinations often fail to define. Conventional procedures for acquisition of a specimen for cytology during ERCP have been limited in their ability to discriminate pancreatic-ductal strictures. OBJECTIVE: Our aim was to discriminate pancreatic-ductal strictures by a new technique of sampling material for cytodiagnosis: scraping cytology with a guidewire. DESIGN: A retrospective study. SETTING: A single cancer center. PATIENTS AND METHODS: Eighty-six patients with pancreatic-ductal strictures composed of 71 malignant and 15 benign diseases were evaluated. Malignant diseases included 70 pancreatic carcinomas and 1 endocrine tumor; benign diseases included the following: 7 chronic pancreatitis, 3 autoimmune pancreatitis, 3 idiopathic pancreatic-ductal strictures, and 2 pancreatic cysts. During ERCP, pancreatic juice was collected with a cannula in the main duct just below the stricture after scraping it with a 0.025-inch hydrophilic guidewire. Cytodiagnosis of the specimen was performed by the Papanicolaou method. MAIN OUTCOME MEASUREMENTS: Diagnostic sensitivities and specificities of scraping cytology with a guidewire for pancreatic carcinoma. RESULTS: Scraping cytology with a guidewire yielded 93% sensitivity, 100% specificity, 100% positive predictive value, 75% negative predictive value, and 94% accuracy. Sensitivities for pancreatic carcinoma in the head, body, and tail of the pancreas were 91%, 100%, and 91%, respectively. Sensitivities for pancreatic carcinoma with a tumor of <20 mm, 21 to 40 mm, 41 to 60 mm, and >61 mm were 95%, 92%, 100%, and 100%, respectively. Pancreatitis subsequent to the procedure occurred in 4 patients (5%), all of whom were cured by conservative treatment. CONCLUSIONS: Benign or malignant pancreatic-ductal strictures were accurately discriminated by scraping cytology with a guidewire during ERCP. The technique yielded high diagnostic sensitivities in pancreatic carcinoma, regardless of the location or size of the tumor.

Analysis of the color patterns of early gastric cancer using an autofluorescence imaging video endoscopy system.

BACKGROUND: Using a novel autofluorescence imaging video endoscopy system (AFI), tumors in the esophagus and the colon appeared purple in a green background, but the color patterns of early gastric cancer (EGC) were found to vary. Factors associated with these patterns remain unknown. The aims of the present study were to classify the color patterns of EGCs and to investigate the correlation between the patterns and clinicopathological features. METHODS: A total of 107 EGCs that had been evaluated by AFI endoscopy, prior to endoscopic or surgical resection, were included. The color patterns of EGCs in AFI images and the association between tumor color and clinicopathological factors were evaluated. These factors included tumor morphology, location, size, background color, histological type, depth of invasion, lymphatic or vessel permeation, and ulceration. RESULTS: The color patterns of EGCs were classified into the following four groups: purple tumors in a green background (52%); green tumors with a purple margin in a green background (21%); green tumors in a purple background (17%); and purple tumors in a purple background (10%). Univariate analysis showed that macroscopic type, histological type, ulceration, and background AFI color were significantly associated with tumor color, whereas multivariate analysis revealed that macroscopic type was the only independent contributor to tumor color. CONCLUSION: The present study has enabled a clearer understanding of the significance of tumor color in relation to the AFI imaging of EGCs. Recognition of the color patterns in AFI images should help in the diagnosis of EGCs.

Cloning of poly(aspartic acid) (PAA) hydrolase-1 gene from Pedobacter sp. KP-2 and hydrolysis of thermally synthesized PAA by its gene product.

Pedobacter sp. KP-2 can degrade and metabolize thermally synthesized alpha,beta-poly(D,L-aspartic acid) (tPAA), which contains 70% of unnatural beta-amide units, with high-molecular-weight. In this study, gene cloning and molecular characterization of PAA hydrolase-1 from KP-2 was carried out. Gene analysis reveals that deduced amino acid sequence of the enzyme shows a similarity to only that of PAA hydrolase-1 from Sphingomonas sp. KT-1. GPC and NMR analyses of the hydrolyzed products of tPAA by PAA hydrolase-1 of KP-2 indicate that this enzyme cleaves the beta-beta amide linkage via endo-mode to yield oligo(aspartic acid) from tPAA. Taking the composition of tPAA and the substrate specificity of PAA hydrolase-1 into consideration, the enzyme possibly plays a crucial role in tPAA biodegradation by KP-2.

Quantitative analysis of the color change after iodine staining for diagnosing esophageal high-grade intraepithelial neoplasia and invasive cancer.

BACKGROUND: Despite its high sensitivity for detecting esophageal cancer, chromoendoscopy with iodine staining has low specificity and requires many biopsy specimens, which is undesirable. Dramatic color change after iodine staining (initially whitish yellow and then pink 2 to 3 minutes later) has come to be recognized as the pink-color sign in cancerous lesions. OBJECTIVE: The aim of the present study was to verify the accuracy of the pink-color sign for diagnosing esophageal squamous neoplasms by a quantitative analysis. DESIGN: A quantitative analysis of endoscopic images was performed by using prospectively pooled data. SETTING: A cancer referral center. PATIENTS: From December 2003 to September 2005, consecutive patients who underwent a procedure by an experienced endoscopist and had iodine-unstained lesions measuring 5 to 20 mm in diameter without obvious protrusions or ulcers were prospectively enrolled. MAIN OUTCOME MEASUREMENTS: The diagnostic ability of the quantitative assessment of the color change at 2 minutes after iodine staining (late phase) was investigated by using a receiver operating characteristic analysis. RESULTS: A total of 45 iodine-unstained lesions in 32 patients were included in the study. Among these, 22 of 23 pink-color-positive lesions were diagnosed as high-grade intraepithelial neoplasias or invasive cancers, whereas 19 of 22 pink-color-negative lesions were diagnosed as nonneoplastic lesions or low-grade intraepithelial neoplasias. The area under the receiver operating characteristic curve was 0.94, indicating excellent validity of the test. A sensitivity of 88% and specificity of 95% were obtained. LIMITATIONS: Single-center retrospective analysis. CONCLUSIONS: We verified the accuracy of the pink-color sign for diagnosing esophageal squamous neoplasms by a quantitative analysis.

Comparison of EMR and endoscopic submucosal dissection for en bloc resection of early esophageal cancers in Japan.

BACKGROUND: EMR and endoscopic submucosal dissection (ESD) are now being increasingly used for the treatment of esophageal cancers. However, their efficacies in smaller lesions have not been compared. OBJECTIVE: For effective use of these methods, we compared the results of ESD and 2 major EMR methods for treating esophageal cancers of

Local recurrence of large squamous-cell carcinoma of the esophagus after endoscopic resection.

BACKGROUND: A new technique, endoscopic submucosal dissection (ESD), which uses specially developed endoscopic knives, was recently developed for en bloc resection of large lesions. Despite increasing indications for endoscopic resection (ER), there are limited data available regarding the outcome of ER for lesions 20 mm or more in diameter. OBJECTIVE: To investigate the risk factors for local recurrence. DESIGN: Retrospective cohort study. SETTING: A cancer-referral center. PATIENTS: Seventy patients, who presented between September 1994 and April 2006, with a total of 78 lesions that measured 20 mm or more in diameter. MAIN OUTCOME MEASUREMENT: Local recurrence rate after ER was assessed. RESULTS: At a median follow-up of 32 months (range 12-121 months), there were 12 local recurrences (15.4%). There was no significant association between local recurrence and multiple iodine-voiding lesions, tumor size, or tumor location. The number of resections and the resection method, however, were significantly associated with local recurrence. There was no recurrence of lesions treated by en bloc resection. Lesions resected in 5 or more pieces had a significantly higher recurrence rate than lesions resected in 2 to 4 pieces. Lesions treated by EMR had a significantly higher recurrence rate than lesions treated by ESD. LIMITATIONS: Single-center retrospective analysis. CONCLUSIONS: Esophageal squamous-cell carcinoma that measured 20 mm or more in diameter should be resected en bloc by ESD. Lesions treated by resection in 5 or more pieces have a higher risk for local recurrence.

Effect of a proton pump inhibitor or an H2-receptor antagonist on prevention of bleeding from ulcer after endoscopic submucosal dissection of early gastric cancer: a prospective randomized controlled trial.

OBJECTIVES: With conventional methods of endoscopic mucosal resection for early gastric cancer (EGC), proton pump inhibitors (PPIs) and H2-receptor antagonists (H2RAs) have a similar effect on preventing bleeding from artificial ulcers. An objective of this study is to investigate whether a stronger acid suppressant (i.e., PPI) more effectively prevents bleeding after the recent advanced technique of endoscopic submucosal dissection (ESD) for EGC. METHODS: This was a prospective randomized controlled trial performed in a referral cancer center. A total of 143 patients with EGC who underwent ESD were randomly assigned to the treatment groups. They received either rabeprazole 20 mg (PPI group) or cimetidine 800 mg (H2RA group) on the day before ESD and continued for 8 wk. The primary end point was the incidence of bleeding that was defined as hematemesis or melena that required endoscopic hemostasis and decreased the hemoglobin count by more than 2 g/dL. RESULTS: In baseline data, the endoscopists who performed the ESD were significantly different between the groups. Finally, 66 of 73 patients in the PPI group and 64 of 70 in the H2RA group were analyzed. Bleeding occurred in four patients in the PPI group and 11 in the H2RA group (P= 0.057). Multivariate analysis revealed that treatment with the PPI significantly reduced the risk of bleeding: adjusted hazard ratio 0.47, 95% confidence interval 0.22-0.92, P= 0.028. One delayed perforation was experienced in the H2RA group. CONCLUSIONS: PPI therapy more effectively prevented delayed bleeding from the ulcer created after ESD than did H2RA treatment.

Anesthetic management of a patient with a history of Batista procedure for dilated cardiomyopathy undergoing gastric surgery.

We experienced anesthetic management for an operation to remove a hemorrhagic gastric submucosal tumor in a patient who had undergone left ventricular volume reduction (the Batista procedure) for dilated cardiomyopathy (DCM) 2 years previously. Preoperative evaluations indicated the relapse of severe DCM. Intravenous and epidural anesthesia was employed with the aid of an intraaortic balloon pump (IABP). Safe anesthetic management was achieved under the guidance of a Swan-Ganz catheter without inducing overreduction of afterload or excessive preload.