Study for determination of the optimal cessation period of therapy with anti-platelet agents prior to invasive endoscopic procedures

Background Anti-platelet agents are widely used for the treatment and prevention of thrombotic diseases. On the other hand, continuation of anti-platelet agents increases the risk of hemorrhagic complications in gastrointestinal endoscopy, and cessation of anti-platelet agents exposes the patient to the risk of thromboembolism. Only a few studies have actually studied the whether a cessation period is required prior to endoscopic procedures and if so, the optional duration of the period. The present study assessed the time course of primary hemostasis after the cessation of anti-platelet agents.Methods Eleven healthy men (age range, 19–29 years) were assigned to each of the following regimens: aspirin (ASA; 100 mg/day), ticlopidine (TP; 300 mg/day), and a combination of ASA (100 mg/day) and TP (300 mg/day) for 7 days. There was a washout period of more than 3 weeks between each regimen. A quantitative bleeding time test (QBT test) and platelet aggregation test were performed before the beginning of administration, on the last day of administration, and at 1, 3, and 5 days after cessation, and also at 7 days after cessation for the combination regimen.Results The average bleeding time (BT) and total bleeding loss volume (Tv) of the 11 subjects after administration of the three regimens were significantly increased compared with those before administration. With the administration of ASA, increases of BT and Tv at 3 days after cessation were not significant. The Tv at 5 days after cessation of TP was not significantly increased. With the combination regimen, the BT and Tv at 7 days after cessation were not significantly increased.Conclusions A 3-day cessation period for ASA, a 5-day cessation period for TP, and a 7-day cessation period for ASA + TP administration seem to be sufficient.     

A murine model of acute liver injury induced by human monoclonal autoantibody

We have previously reported an immunoglobulin (Ig) M autoantibody to hepatocyte-related 190-kd molecules in patients with type 1 autoimmune hepatitis (AIH). This molecule was first isolated by hepatocyte-specific human monoclonal antibody (MoAb). To elucidate the role of this IgM autoantibody in hepatocyte injury, we examined the reactivity of this MoAb to murine hepatocytes and then questioned whether acute hepatic injury could be induced in mice via injection of this MoAb. The reactivity of MoAb was examined via both FACS analysis using murine hepatocytes and immunostaining of liver tissues. We then identified the murine hepatocyte membrane molecule recognized by this MoAb. The role of this MoAb in the immunopathogenesis of AIH was assessed by testing whether its injection into mice could increase serum aminotransferase levels as well as cause changes in liver histology. The present results demonstrate that this MoAb cross-reacted with murine hepatocytes and recognized a 190-kd molecule on the murine hepatocyte membrane just as in human hepatocytes. One hour after the injection of MoAb, the deposition of both IgM and complement component 3 was found in liver tissues. At 8 hours after the injection, serum aminotransferase levels were significantly increased in MoAb-injected mice compared with controls. Histological study revealed massive hepatocyte necrosis in MoAb-injected mice. In conclusion, human MoAb recognized a 190-kd molecule of both human and murine hepatocytes, and the injection of this MoAb to mice resulted in acute liver injury, indicating that this type of autoantibody may play an important role in the immunopathogenesis of AIH.     

Transient elastography-derived liver stiffness measurements were found to be useful for predicting liver infiltration in a case of mature T-cell neoplasm involving liver dysfunction

Transient elastography (TE) is a novel, non-invasive imaging technique for measuring liver stiffness (LS). It is considered to be useful for predicting the severity of fibrosis and the risk of cirrhosis or hepatocellular carcinoma. However, the association between the presence of diffuse regions of increased cell density in the liver and elevated LS values has not been assessed. We experienced a case in which a mature T-cell neoplasm had invaded the liver, but the infiltrating lesion was not detected by contrast-enhanced computed tomography (CT) or fluorodeoxyglucose positron emission tomography/CT scans. Instead, the tumor’s presence was indicated by the change in the patient’s TE-derived LS values after chemotherapy. At diagnosis liver dysfunction was detected in a biochemical examination, and mean LS value was as high as 25.4 kPa [interquartile range (IQR): 0.3, success rate (SR):100%]. After chemotherapy, the patient’s mean LS value fell to 4.3 kPa (IQR: 0.8, SR:100%). A follow-up pathological investigation demonstrated that proliferating abnormal T-cells were no longer present in the patient’s liver. This is the first report to describe the use of LS data to support a diagnosis of liver infiltration by tumor cells exhibiting a portal and sinusoidal distribution pattern rather than a focal pattern. Elevated TE-derived LS values should lead to hepatic tumor infiltration being considered during initial examinations or a suspicion of recurrence during follow-up examination of lymphoma patients who achieve complete remission, even when radiological investigations do not detect abnormalities in the liver.     

Perioperative outcomes of esophagectomy preceded by the laparoscopic transhiatal approach for esophageal cancer

This study was designed to determine the efficacy of esophagectomy preceded by the laparoscopic transhiatal approach (LTHA) with regard to the perioperative outcomes of esophageal cancer. The esophageal hiatus was opened by hand‐assisted laparoscopic surgery, and carbon dioxide was introduced into the mediastinum. Dissection of the distal esophagus was performed up to the level of the tracheal bifurcation. En bloc dissection of the posterior mediastinal lymph nodes was performed using LTHA. Next, cervical lymphadenectomy, reconstruction via a retrosternal route with a gastric tube and anastomosis from a cervical approach were performed. Finally, a small thoracotomy (around 10 cm in size) was made to extract the thoracic esophagus and allow upper mediastinal lymphadenectomy to be performed. The treatment outcomes of 27 esophageal cancer patients who underwent LTHA‐preceding esophagectomy were compared with those of 33 patients who underwent the transthoracic approach preceding esophagectomy without LTHA (thoracotomy; around 20 cm in size). The intrathoracic operative time and operative bleeding were significantly decreased by LTHA. The total operative time did not differ between the two groups, suggesting that the abdominal procedure was longer in the LTHA group. The number of resected lymph nodes did not differ between the two groups. Postoperative respiratory complications occurred in 18.5% of patients treated with LTHA and 30.3% of those treated without it. The increase in the number of peripheral white blood cells and the duration of thoracic drainage were significantly decreased by this method. Our surgical procedure provides a good surgical view of the posterior mediastinum, markedly shortens the intrathoracic operative time, and decreases the operative bleeding without increasing major postoperative complications.     

Gastroesophageal reflux disease and patterns of reflux in patients with idiopathic pulmonary fibrosis using hypopharyngeal multichannel intraluminal impedance

Idiopathic pulmonary fibrosis (IPF) is a diffuse fibrotic lung disease of unknown etiology. The association between IPF and gastroesophageal reflux disease (GERD) has been suggested. The objective of this study was to determine the prevalence of GERD and assess the proximity of reflux events in patients with histologically proven IPF using hypopharyngeal multichannel intraluminal impedance (HMII). This is a retrospective review of prospectively collected data from patients with histologically confirmed IPF (via lung biopsy) who underwent objective esophageal physiology testing including high‐resolution manometry and HMII. Defective lower esophageal sphincter (LES) was defined as either LES pressure of <5.0 mmHg, total length of LES of <2.4 cm, or intra‐abdominal length of LES of <0.9 cm. Abnormal esophageal motility was considered present when failed swallows ≥30% and/or mean wave amplitude <30 mmHg was present. HMII used a specialized impedance catheter to directly measure laryngopharyngeal reflux (LPR) and full column reflux (reflux 2 cm distal to the upper esophageal sphincter). Based on the previous study of healthy subjects, abnormal proximal exposure was considered present when LPR ≥1/day and/or full column reflux ≥5/day were present. From October 2009 to June 2011, 46 patients were identified as having pulmonary fibrosis and sufficient HMII data. Of 46, 10 patients were excluded because of concomitant connective tissue diseases, and 8 patients were excluded because they had undergone lung transplantation, which may impact the patterns of reflux. The remaining 28 patients with histologically confirmed IPF (male 16, female 12) were included in this study. Mean age and BMI were 60.4 years (range, 41–78) and 28.4 (range, 21.1–38.1), respectively. All patients except one were symptomatic; 23 (82%) patients had concomitant typical GERD symptoms such as heartburn, whereas 4 (14%) patients had isolated pulmonary symptoms such as cough. Esophageal mucosal injury such as esophagitis and Barrett's esophagus was found in 17 (71%) patients, whereas hiatal hernia was found in 19 (73%) patients. Abnormal proximal exposure, which occurred almost exclusively in the upright position, was present in 54% (15/28) of patients. There was no significant difference in clinical symptoms, objective findings of GERD, and pulmonary functions such as forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and diffusing capacity of the lung for carbon monoxide (DLCO) between patients with and without abnormal proximal exposure. Although the total number of reflux events was significantly higher in patients with abnormal proximal exposure, a large number of patients had a negative DeMeester score regardless of whether abnormal proximal exposure was present (patients with, 80%; those without, 85%). Patients with abnormal proximal exposure more likely had a defective LES compared with those without (93% vs. 75%). Fourteen patients (56%) had abnormal esophageal motility including aperistaltic esophagus (n = 9). This first study of HMII in patients with IPF demonstrated that GERD is highly prevalent (>70%), and abnormal proximal reflux events such as LPR and full column reflux are common despite a frequently negative DeMeester score. HMII may be beneficial in the work‐up of GERD in patients with IPF.