Chemokine receptor CCR6 as a prognostic factor after hepatic resection for hepatocellular carcinoma

Background and Aims: Chemokines and their receptors have recently been shown to have major roles in cancer metastasis. The aim of this study was to determine whether the interaction between chemokine receptor 6 (CCR6) and its ligand, macrophage inflammatory protein‐3 alpha (MIP‐3α), correlates with metastasis of hepatocellular carcinoma (HCC). Methods: To observe the reaction of CCR6 expressed cancer cells to MIP‐3α stimulation, chemotactic and actin polymerization assays for both CCR6 high cells (HepG2) and CCR6 low cells (MCF‐7) were performed. CCR6 mRNA levels in tumor specimens from 30 HCC patients were quantified by real‐time polymerase chain reaction. Patients were classified into two groups, high (≥ 20 copies; n = 10) CCR6 and low (<20 copies; n = 20) CCR6 on the basis of CCR6 expression, and the groups were compared with respect to clinicopathological features. Results: When HepG2 cells (CCR6 high) were stimulated with MIP‐3α, they migrated in a dose‐dependent manner, and formation of pseudopodia was observed. These phenomena were not observed in the CCR6 low cells. The incidence of intrahepatic metastasis was higher in the high CCR6 expression group than in the low CCR6 expression group (P < 0.05). Disease‐free survival was significantly poorer in the high CCR6 expression group than in the low CCR6 expression group (P < 0.05). Conclusions: It was indicated that CCR6 might be associated with intrahepatic metastasis of HCC and might be able to become one of the prognostic factor after hepatic resection for HCC.     

Microvascular disturbances in the colonic mucosa in antibiotic-associated haemorrhagic colitis: Involvement of platelet aggregation

An ultrastructural study of the colonic mucosa was performed in four patients with antibiotic-associated haemorrhagic colitis and new findings are reported. Colonoscopy was performed and biopsy specimens were obtained within 24 h of the onset of bloody diarrhoea. Colonoscopy demonstrated diffuse oedematous and haemorrhagic mucosa with erosions and white coat. Light microscopy revealed mucosal haemorrhage and inflammatory cell infiltration. Ultrastructurally, platelet aggregation was frequently present in the lumina of colonic mucosal capillaries, causing engorgement of red blood cells in adjacent microvessels. Mild to severe damage was observed in capillary endothelial cells, including discontinuity of basement membranes, gaps between endothelial cells and the destruction of capillaries. There was no evidence of microvascular spasm. In conclusion, our findings suggest that antibiotics directly or indirectly cause microcirculatory disturbances, which result in tissue damage and haemorrhage, in the colonic mucosa.     

Bacterial invasion into the colonic mucosa in ulcerative colitis

Abstract This study investigated interactions between mucosal lesions and bacterial invasion in ulcerative colitis using the acridine-orange staining method. In all 16 cases of ulcerative colitis, the mucosa was found to be invaded by small rods and cocci. In five of 10 controls, bacteria were seen only adhering to the mucosa and no bacteria were detected in the five remaining cases. It is suggested that the presence of bacteria in the colonic mucosa may be a factor responsible for the persistence or aggravation of ulcerative colitis.     

Jaundice and Renal Failure Following Radical Surgery for Cancer: An Analysis of Five Autopsied Cases

An analysis of postoperative jaundice and renal failure in fiveautopsied cases is presented. Two patients had total resectionof esophageal cancer, one had a subtotal gastrectomy, and theother two had radical operations for urinary bladder carcinoma.Halothane was used for anesthesia for three patients, and allfive required blood transfusions. Postoperatively, jaundiceand azotemia developed between the 1st and 7th days, with deathsix to 10 days after surgery. Total bilirubin ranged from 1.5to 13.4mg/dl despite the normal or modest rise in hepatic enzymes.BUN varied from 46 to 288 mg/dl. Pre- and postoperative ECGrevealed a prolongation of QTc in all cases. At autopsy, theliver, kidneys and heart showed a definite increase in weight.The salient hepatic pathology included diffusely dilated spaceof Disse, centrilobular bile stasis and steatosis. This, alongwith acute tubular necrosis confirmed at autopsy, was thoughtto be due to ischemia. Although the significance of prolongedQTc remains uncertain, it is worthy of attention as one of thepreoperative checks.     

Urodynamic effects and safety of modified intravesical oxybutynin chloride in patients with neurogenic detrusor overactivity: 3 years experience

BACKGROUND: Intravesical oxybutynin chloride with hydroxypropylcellulose (HPC) (modified intravesical oxybutynin) has been reported to be effective for treatment of overactive bladder. We reported the short-term effects of modified intravesical oxybutynin previously. In the present article, we detail the results of a 3-year follow-up study of patients from our previous analysis and report the efficacy and side-effects of modified intravesical oxybutynin. METHODS: Modified intravesical oxybutynin (5 mg/10 mL, twice a day) was applied for more than 3 years to six neurogenic overactive detrusor patients (three men and three women, average age 53.3 years) who were not satisfied with oral anticholinergic agents or the other therapy. A cystometogram (CMG) was performed before, 1 week after and 3 years after the start of modified intravesical oxybutynin treatment. We evaluated the patient's satisfaction of this treatment after 4 weeks and again after 3 years. We compared the patients' answers before and after the therapy (excellent, good, fair, unchanged and worse). We also monitored systemic and topical side-effects in these patients during this period. RESULTS: CMG studies showed that two of six patients no longer exhibited uninhibited contraction 1 week after the treatment and that the cystocapacity of patients before, 1 week after and 3 years after the initial modified intravesical oxybutynin was 129.7 +/- 19.4, 283.5 +/- 40.4 and 286.8 +/- 38.1 mL, respectively. For the evaluation of patients' satisfaction with this treatment, four patients considered the therapy excellent and one patient described it as good after both 4 weeks and after 3 years. Two patients dropped out of the study; one developed left ureteral cancer (2.25 years) and the other developed ileus (1.5 years). Dry mouth and acute cystitis were observed in both patients. CONCLUSION: Modified intravesical oxybutynin is an effective and relatively safe option of therapy for overactive bladder patients. However, this therapy requires careful observation for emergent side-effects.     

A Case of Esophageal Carcinoma and Collision Tumor of the Stomach

A case of double primary cancer of the esophagus and stomachwith metastasis of the esophageal cancer to the stomach is reported.The entire stomach and the lower part of the esophagus weresurgically resected and intrathoracic esophagojejunostomy wasperformed. Macroscopically, two tumors were found to be present,both in the lower esophagus and the stomach. There were twoprimary cancers, one a squamous cell carcinoma of the esophagusand the other a collision tumor of the stomach which consistedof well-differentiated adenocarcinoma and signet ring cell carcinoma.Furthermore, this collision tumor was present together witha metastatic lesion from the esophageal carcinoma.     

Racemization studies in peptide synthesis through the separation of protected epimeric peptides by reversed-phase high performance liquid chromatography

Separation of protected epimeric peptides, Z-Gly-Xaa-Xbb-OMe (where Xaa and Xbb = chiral amino acid residues), by reversed-phase HPLC was utilized for studying racemization in peptide synthesis. Thus, the following factors which might affect the extent of racemization during the coupling by the carbodiimide method were investigated: the combination of amino acid residues to be coupled, coexisting tertiary amine salts, and the relative configuration of the amino acid residues. The following points were revealed: the combination of bulky residues at the coupling site results in extensive racemization in a polar solvent such as DMF, the amine hydrochlorides cause less racemization than the p-toluenesulfonates in DMF, and the influence of relative configuration differs depending on the solvent and the individuality of the amino components. Furthermore, the racemization-suppressing effect of some additives in the carbodiimide method was reevaluated by employing the same procedure.     

Electrophysiological Abnormalities of the Atrial Muscle in Patients with Manifest Wolff-Parkinson-White Syndrome Associated with Paroxysmal Atrial Fibrillation

We investigated the electrophysiological properties of the atrial muscle in 33 patients with manifest Wolff-Parkinson-White syndrome. Group I consisted of 13 patients with paroxysmal atrial fibrillation and group II consisted of 20 patients without paroxysmal atrial fibrillation. The anterograde and retrograde effective refractory periods of the accessory pathway and the inducibility of atrioventricular reciprocating tachycardia were not significantly different between the two groups. Endocardial electrograms, obtained by right atrial catheter mapping, were recorded during sinus rhythm from 12 sites of the right atrium in 12 of the 13 group I patients and in all group II patients. An abnormal atrial electrogram was defined as 100 msec or longer in duration, and/or the occurrence of eight or more deflections. Ten (83%) of the 12 group I patients had abnormal atrial electrograms, while only two (10%) of the 20 group II patients had abnormal atrial electrograms, and the difference was significant (P less than 0.01). Thirty-six (26%) of the total 139 electrograms obtained from 12 group I patients and two (1%) of the total 199 electrograms obtained from 20 group II patients fulfilled the criteria for an abnormal atrial electrogram, and the difference was significant (P less than 0.01). The fragmented atrial activity zone, interatrial conduction delay zone, and repetitive atrial firing zone obtained by right atrial extrastimulation were significantly wider in group I than in group II, respectively. It was concluded that electrical abnormalities of the atrial muscle may play an important role in the occurrence of paroxysmal atrial fibrillation in patients with Wolff-Parkinson-White syndrome.