CASE OF INFLAMMATORY FIBROID POLYP OF THE ESOPHAGOGASTRIC JUNCTION

Upper gastrointestinal endoscopy of a 25‐year‐old man with heartburn revealed an elevated lesion in the esophagogastric junction (EGJ). Piecemeal endoscopic mucosal resection (EMR) followed by histopathological examination led to a diagnosis of inflammatory fibroid polyp (IFP). After EMR, the heartburn persisted despite giving a proton pump inhibitor (PPI), and the residual lesion gradually enlarged and a transverse mucosal break developed on the esophageal side of it. However, the combined administration of the PPI and an H2 receptor antagonist reduced the heartburn, and led to endoscopic regression of the lesion and disappearance of the transverse mucosal break. IFP of the esophagogastric junction is extremely rare, and this case is interesting in that potent inhibition of gastric acid secretion resulted in the regression of the lesion.     

From the Cover: Arginine ADP-ribosylation mechanism based on structural snapshots of iota-toxin and actin complex

Clostridium perfringens iota-toxin (Ia) mono-ADP ribosylates Arg177 of actin, leading to cytoskeletal disorganization and cell death. To fully understand the reaction mechanism of arginine-specific mono-ADP ribosyl transferase, the structure of the toxin-substrate protein complex must be characterized. Recently, we solved the crystal structure of Ia in complex with actin and the nonhydrolyzable NAD⁺ analog βTAD (thiazole-4-carboxamide adenine dinucleotide); however, the structures of the NAD⁺-bound form (NAD⁺-Ia-actin) and the ADP ribosylated form [Ia-ADP ribosylated (ADPR)-actin] remain unclear. Accidentally, we found that ethylene glycol as cryo-protectant inhibits ADP ribosylation and crystallized the NAD⁺-Ia-actin complex. Here we report high-resolution structures of NAD⁺-Ia-actin and Ia-ADPR-actin obtained by soaking apo-Ia-actin crystal with NAD⁺ under different conditions. The structures of NAD⁺-Ia-actin and Ia-ADPR-actin represent the pre- and postreaction states, respectively. By assigning the βTAD-Ia-actin structure to the transition state, the strain-alleviation model of ADP ribosylation, which we proposed previously, is experimentally confirmed and improved. Moreover, this reaction mechanism appears to be applicable not only to Ia but also to other ADP ribosyltransferases.     

Pouch operation for rectal cancer

Many retrospective studies have found that the functional outcome after a low anterior resection for rectal cancer is better with colonic J-pouch reconstruction than with conventional straight anastomosis. This advantage was demonstrated in prospective, randomized trials and meta-analyses. However, despite its increasing popularity there are several areas of controversy about the use of the colonic J-pouch reconstruction. These issues include anastomotic leaks, the part of the colon used for the pouch, the pouch size, causes of difficulty in evacuation, indications (the optimum level of anastomosis), appropriateness for the elderly, and long-term (2 years or more after surgery) functional outcome. All relevant articles identified from MEDLINE databases were reviewed. The incidence of anastomotic leaks is apparently reduced by colonic J-pouch reconstruction. A 5-cm colonic J-pouch using the sigmoid colon increases the reservoir function without compromising evacuation, and provides better functional outcome than straight anastomosis, even 2 years or more after surgery, in patients whose anastomosis is less than 8 cm from the anal verge. Patients with ultralow anastomoses, less than 4 cm from the verge, appear to benefit the most. At a time when the indications for abdominoperineal excision appear to be reduced for low rectal cancer, the demand for colonic J-pouch reconstruction (the best technique in pouch operations) is therefore likely to increase.     

Factors on delayed recovery of otitis media with effusion in children--clinical and bacteriological study

The resolution of middle ear effusions (MEE) of children with otitis media with effusion (OME) who underwent myringotomy for the bacteriological examination was analyzed in terms of the culture results and the clinical features. The present study consisted of 193 children (258 ears), and the MEE from 77 ears (30%) were culture positive and the respiratory pathogens were detected from 44 ears (17%). Each child was then assigned to receive either a more than two-week course of antibiotics, cefaclor (CCL) or not. At one month following entry, 53 (55%) out of 97 ears in CCL-treated group were effusion-free compared with 31 (40%) out of 78 ears in the control group (P less than 0.05). In the control group, the resolution of MEE was significantly poor in the recurrent cases and the cases with pathogen positive-MEE. The presence of accompanying diseases such as adenoid vegetation, chronic sinusitis and allergy, however, was not related to the resolution of MEE. On the other hand, the cure rate of the cases with pathogen positive-MEE and recurrent cases in the CCL-treated group showed significant improvement. Furthermore, the cases accompanying adenoid vegetation and chronic sinusitis tended to become effusion-free after the antibiotic treatment. Therefore, the persistent bacterial infection in the middle ear and/or surrounding organs such as adenoid plays possibly an important role in the delayed recovery of OME. Antibiotics treatment could increase, to some extent, the resolution of MEE in cases with OME.     

Clinical Response to Systemic Combined Chemotherapy with 5-Fluorouracil and Cisplatin (FP Therapy) in Patients with Advanced Pancreatic Cancer

Pancreatic cancer shows high mortality and has a poor prognosis.Although the rate of response to all chemotherapeutic regimensis low, some patients have shown improvement of their symptomsafter chemotherapy and/or radiotherapy without obvious tumorregression. We assessed the clinical benefit of systemic combinedchemotherapy with 5-fluorouracil and cisplatin (FP therapy)in 21 patients with advanced cancer of the pancreas. The clinicalresponse to FP therapy was evaluated using two parameters: pain(intensity of pain and consumption of morphine) and performancestatus. A patient was considered to be a clinical responderif one of two parameters was positive and the other was positiveor stable. Four patients (19%) responded. Two of the respondersachieved partial response according to the objective tumor response,and the remaining two showed no change. The survival periodin responders was significant longer than in the other patients.The clinical response may be one parameter for evaluating theresults of treatment for pancreatic cancer, and the longer survivalperiod of the clinical responders in this study supports thisnotion.     

Chronic evaluation of the Cleveland Clinic CorAide left ventricular assist system in calves

The Cleveland Clinic CorAide left ventricular assist system is based on a third-generation, implantable, centrifugal pump in which a rotating assembly is suspended fully. To evaluate chronic in vivo system performance and biocompatibility, the CorAide blood pump was implanted in 18 calves for either 1 month or 3 months. Hemodynamics were stable in all calves with a mean pump flow of 5.9 +/- 1.2 L/min and a mean systemic arterial pressure of 98 +/- 5 mm Hg. There were no incidences of bleeding, organ dysfunction, or mechanical failure in any of the 18 calves. Hemolysis occurred in only 1 calf due to outflow graft stenosis. Thrombus inside the pump, seen in 4 of the first 6 cases, was totally eliminated by a final redesign in the remaining cases, including the last 6 implants conducted without anticoagulation therapy. The CorAide blood pump demonstrated good biocompatibility and reliable, effective system performance.     

Clinicopathological prognostic factors and impact of surgical treatment of mass-forming intrahepatic cholangiocarcinoma

The clinicopathological characteristics relevant to prognosis after surgical treatment of intrahepatic cholangiocarcinoma (ICC) remain unclear. In this study, the clinicopathological features of 19 patients with mass-forming ICC, the most common form of the disease, were reviewed to analyze prognostic determinants. Two or more segmentectomies of the liver with systematic lymphadenectomy were performed in 18 patients. Resection of the extrahepatic bile duct was performed in 14 patients, and reconstruction of the portal vein was accomplished in 5 patients. Stage IVA or IVB tumors were seen in 13 patients, and lymph node (LN) metastasis was present in 14 patients. The estimated 5-year survival rate after surgery for mass-forming ICC was 28%, with median survival time of 18 months. In univariate analysis, five variables were determined to be significantly correlated with poor survival of patients with mass-forming ICC after surgery. These variables include mass-forming ICC with periductal infiltration, perineural invasion, portal vein invasion, presence of intrahepatic metastasis, and two or more LN metastases. Survival rates of 5 patients without LN metastasis and 6 patients with a single LN metastasis were 80% and 33% at 5 years, respectively, while 8 patients with two or more LN metastasis failed to survive beyond 2 years. Multivariate analysis revealed the presence of intrahepatic metastasis to be an independent prognostic factor of poor survival. Hepatectomy with resection of the extrahepatic bile duct and systematic lymphadenectomy yields a good chance for prolonged survival for patients with mass-forming ICC when the lesion is singular and LN metastasis is limited to a regional LN. Because the presence of intrahepatic metastasis was closely related to a poor prognosis in patients with mass-forming ICC, efficacious chemotherapy would be needed to control development of the lesion.     

Lack of alpha 2-antiplasmin promotes re-endothelialization via over-release of VEGF after vascular injury in mice

We here report that the arterial blood flow after endothelial injury in mice deficient in alpha 2-antiplasmin (alpha 2-AP-/- mice) was well maintained compared with that of wild-type mice. Moreover, the development of neointima 4 weeks after injury in alpha 2-AP-/- mice was significantly decreased. Histologic observations showed a prompt recovery of endothelial cells with a much higher proliferating index in repaired endothelium in alpha 2-AP-/- mice. The amount of secreted vascular endothelial growth factor (VEGF) by explanted vascular smooth muscle cells (SMCs) from alpha 2-AP-/- mice was significantly increased. In separate experiments using a human endothelial cell (EC) line, we could demonstrate that plasminogen binds to ECs and that this binding can be prevented by alpha 2-AP. Finally, an injection of either an anti-VEGF receptor-1 antibody or alpha 2-AP reduced the prompt endothelial healing. alpha 2-AP is the main inactivator of plasmin, which cleaves extracellular matrix-bound VEGF to release a diffusible proteolytic fragment. Lack of alpha 2-AP, therefore, could lead to a local over-release of VEGF by the continuously active plasmin in the injured area, which could result in a prompt re-endothelialization after vascular injury. Our results provide new insight into the role of alpha 2-AP and VEGF in the pathogenesis of re-endothelialization following vascular injury.     

Successful treatment of radiation-induced brain necrosis by hyperbaric oxygen therapy

We describe a 68-year-old man who underwent hyperbaric oxygen (HBO) therapy to manage radiation necrosis of the brain, which developed after two treatments with stereotactic radiosurgery (SRS) to the same lesion. The necrosis was subsequently treated with steroids alone for 2 months; however, he progressed clinically and radiographically. Improvement again was noted with the reinstitution of HBO therapy. This case suggests that HBO therapy is an important therapeutic option in the treatment of brain radiation necrosis caused by SRS.