A case of rebamipide-induced pneumonitis]

A 75-year-old man who complained of progressive dyspnea was admitted to our hospital. He had been treated with rebamipide at an outpatient clinic for the preceding seven months. Atrial blood gas values obtained on admission indicated hypoxemia. Chest radiographs and CT films revealed diffuse interstitial infiltration and minimal pleural effusion. Bronchoalveolar lavage fluid showed an increase in the total cell number, the percentages of eosinophils and lymphocytes, and a decrease in the CD4/CD8 ratio. Transbronchial lung biopsy specimens had thickened alveolar septa with lymphocyte infiltration within the air spaces. After the discontinuation of rebamipide, oral prednisolone was administered, and the patient's symptoms and pulmonary shadows quickly improved. A lymphocyte stimulating test for rebamipide was positive. A challenge test for rebamipide was not performed because informed consent could not be obtained. On the basis of these findings, our diagnosis was rebamipide-induced pneumonitis.     

Natural saline-flush is sufficient to maintain patency of immobilized-urokinase double-lumen catheter used to provide temporary blood access for hemodialysis

BACKGROUND: Thrombotic occlusion is a frequent complication of central venous catheters used to provide temporary blood access on hemodialysis therapy. Heparin-lock is conventionally used to maintain patency of the catheter, but the necessity of heparin-lock has not been determined yet. METHODS: After the immobilized-urokinase double-lumen central venous catheter was inserted into 48 Japanese hemodialysis patients, 22 patients randomized to the heparin group received a 20-ml saline-flush, followed by 2 ml of 1,000 U/ml heparin-lock, and 26 patients randomized to the saline group received only the 20-ml saline-flush once a day for each lumen. RESULTS: Thrombotic occlusion was observed in only 1 out of 22 patients in the heparin group and 1 out of 26 patients in the saline group. No significant difference of the catheter survival was observed between the two groups (p = 0.8599). CONCLUSIONS: Natural saline-flush is sufficient for maintaining the patency of an immobilized-urokinase double-lumen central venous catheter.     

Efficacy of anatomic resection vs nonanatomic resection for small nodular hepatocellular carcinoma based on gross classification

Background/Purpose

It has been reported that anatomic resection may be preferable to nonanatomic resection for small hepatocellular carcinomas (HCCs), by reducing socalled “micrometastases” (portal venous tumor extension and intrahepatic metastases). Nonanatomic resection or ablation has also been used as therapy for small HCCs. We studied the effectiveness of anatomic resection for small nodular HCCs, especially from the viewpoints of tumor size and gross classification.

Methods

A retrospective cohort study was performed in 116 consecutive patients who underwent curative hepatic resection for HCCs 3 cm or smaller and with three or fewer nodules. The outcome of anatomic resection (including segmentectomy, sectoriectomy, and hemihepatectomy) was compared to that of nonanatomic partial hepatectomy.

Results

The group that underwent anatomic resection (n = 52) had relatively better overall survival and significantly better recurrence-free survival than those with nonanatomic resection (n = 64). On Cox multivariate analysis, however, liver function was more closely associated with survival. The effect of anatomic resection was more prominent in the subgroup with the nonboundary type nodules (single nodular type with extranodular growth, confluent multinodular type, and invasive type) than in the subgroup with the boundary type (vaguely nodular and single nodular type). Micrometastases in the nonboundary type were found further from the main tumor (9.5 ± 6.2 mm) than those in the boundary type (within 3.1 +-1.4 mm).

Conclusions

In patients with HCC nodules equal to or less than 3 cm and with the nonboundary type, anatomic resection should be employed to the extent that liver function allows, because this procedure would be more favorable than nonanatomic resection in eradicating micrometastases that have extended away from the tumor’s margin.     

MCP-1 and MIP-1A gene polymorphisms in Japanese patients with sarcoidosis

OBJECTIVES: Monocyte chemoattractant protein (MCP)-1 and macrophage inflammatory protein (MIP)-1alpha exhibit chemotactic activity toward macrophages/monocytes and induce the production of inflammatory cytokines affecting granuloma formation. Recently, a single nucleotide polymorphism (SNP) in the MCP-1 distal regulatory region and a dinucleotide repeat in the MIP-1A gene promoter region were identified. We investigated the relationships between the polymorphisms and susceptibility to sarcoidosis, clinical manifestations, and BALF findings of sarcoidosis. METHODS: The polymorphisms of the MCP-1 and MIP-1A genes in 118 patients with sarcoidosis and 145 healthy control subjects were examined. The MCP-1 polymorphism was genotyped by a PCR-restriction fragment length polymorphism method and the MIP-1A genotype was determined using PCR. RESULTS: No significant difference in the genotype distribution or in the allele frequency between the patients and control subjects was observed. We found no relationship between the polymorphisms and the serum ACE level, organ involvement, roentgenographic stages, or deterioration in chest radiographs during the follow-up. A significant difference in the absolute counts of AMs in BALF of 51 patients among the genotypes of the MCP-1 gene was found (p = 0.048). The AM counts in BALF of the G/A and G/G genotypes were significantly increased compared with that of the A/A genotype (p < 0.05). CONCLUSION: The polymorphisms of the MCP-1 and MIP-1A genes do not play a substantial role in genetic predisposition for sarcoidosis or in clinical manifestations of sarcoidosis in this Japanese population. The MCP-1 SNP might be related to the recruitment of monocytes/macrophages to the alveolar spaces in sarcoidosis.     

A nephropathy presenting the microparticles in the glomerular basement membrane in a patient of hepatitis B viral infection

We report here unique electron microscopy findings showing clusters of deposition of spherical and tubular microparticles in a glomerular basement membrane (GBM) of a 46-year-old Japanese male with membranous nephropathy. Another distinct feature was the deep infolding of podocyte membranes into the GBM. Light microscopy showed the ladder formation of the GBM suggesting membranous nephropathy, while the immunofluorescent examination was atypical for the absence of the global capillary deposition of IgG and C3. He had mild liver dysfunction with positive hepatitis B antigen. Antibodies to hepatitis B surface antigen reacted weakly on the GBM in the immunohistochemistry. We suspected the unique findings of this case might be related to the hepatitis B viral infection.     

Efficacy of anatomic resection vs nonanatomic resection for small nodular hepatocellular carcinoma based on gross classification

Background/Purpose  It has been reported that anatomic resection may be preferable to nonanatomic resection for small hepatocellular carcinomas (HCCs), by reducing socalled “micrometastases” (portal venous tumor extension and intrahepatic metastases). Nonanatomic resection or ablation has also been used as therapy for small HCCs. We studied the effectiveness of anatomic resection for small nodular HCCs, especially from the viewpoints of tumor size and gross classification. Methods  A retrospective cohort study was performed in 116 consecutive patients who underwent curative hepatic resection for HCCs 3 cm or smaller and with three or fewer nodules. The outcome of anatomic resection (including segmentectomy, sectoriectomy, and hemihepatectomy) was compared to that of nonanatomic partial hepatectomy. Results  The group that underwent anatomic resection (n = 52) had relatively better overall survival and significantly better recurrence-free survival than those with nonanatomic resection (n = 64). On Cox multivariate analysis, however, liver function was more closely associated with survival. The effect of anatomic resection was more prominent in the subgroup with the nonboundary type nodules (single nodular type with extranodular growth, confluent multinodular type, and invasive type) than in the subgroup with the boundary type (vaguely nodular and single nodular type). Micrometastases in the nonboundary type were found further from the main tumor (9.5 ± 6.2 mm) than those in the boundary type (within 3.1 +-1.4 mm). Conclusions  In patients with HCC nodules equal to or less than 3 cm and with the nonboundary type, anatomic resection should be employed to the extent that liver function allows, because this procedure would be more favorable than nonanatomic resection in eradicating micrometastases that have extended away from the tumor’s margin.     

Daytime hypoxemia, sleep-disordered breathing, and laryngopharyngeal findings in multiple system atrophy

BACKGROUND: The mechanism underlying nocturnal sudden death in patients with MSA remains unclear. It may be explained by upper airway obstruction, such as vocal cord abductor paralysis; an impairment of the respiratory center, such as Cheyne-Stokes respiration; or an impaired hypoxemic ventilatory response. OBJECTIVE: To investigate the mechanism of sleep-disordered breathing in multiple system atrophy (MSA). DESIGN: We recruited 21 patients with probable MSA who were admitted sequentially to our hospital, and performed daytime blood gas analysis, pulmonary function tests, polysomnography, and fiberoptic laryngoscopy during wakefulness and with the patient under anesthesia. RESULTS: A decrease in arterial oxygen pressure and an increase in alveolar-arterial oxygen gradient significantly correlated with disease duration (P = .045 and .046, respectively). Polysomnography demonstrated Cheyne-Stokes respiration in 3 (15%) of 20 patients. Fiberoptic laryngoscopy during wakefulness showed that 3 (14%) of the 21 patients exhibited vocal cord abductor paralysis, and laryngoscopy under anesthesia showed that 9 (45%) of 20 patients exhibited vocal cord abductor paralysis. Laryngoscopy under anesthesia also revealed that 11 (55%) of 20 patients showed upper airway obstruction in places other than the vocal cords, including obstruction at the base of the tongue or soft palate. In addition, it demonstrated novel laryngopharyngeal findings, such as floppy epiglottis and airway obstruction at the arytenoid. CONCLUSIONS: We observed daytime hypoxemia with an increased alveolar-arterial oxygen gradient, Cheyne-Stokes respiration, and novel abnormal laryngopharyngeal movements in patients with MSA. We also found that laryngoscopy under anesthesia might be useful for evaluating upper airway obstruction. The significance of these findings to the mechanism of sudden death in those with MSA needs to be examined.     

Surgical resection versus radiofrequency ablation for small hepatocellular carcinomas within the Milan criteria

Background/Purpose  It has been reported that hepatic resection may be preferable to other modalities for the treatment of small hepatocellular carcinomas (HCCs), by contributing to improved overall and disease-free survival. Ablation techniques such as radiofrequency ablation (RFA) have also been used as therapy for small HCCs; however, few studies have compared the two treatments based on long-term outcomes. The effectiveness of hepatic resection and RFA for small nodular HCCs within the Milan criteria were compared. Methods  A retrospective cohort study was performed with 278 consecutive patients who underwent curative hepatic resection (n = 123) or initial RFA percutaneously (n = 110) or surgically (thoracoscopic-, laparoscopic-, and open-approaches; n = 45) for HCC. The selection criteria for treatment were based on uniform criteria. Mortality related to therapy and 3- and 5-year overall and disease-free survivals were analyzed. Results  The model for endstage liver disease (MELD) scores for all patients in the series were less than 13. There were no therapy-related mortalities in either the hepatic resection or RFA groups. The incidence of death within 1 year after therapy (1.6 and 1.9%, respectively) was similar in the hepatic resection and RFA groups. The group that underwent hepatic resection showed a trend towards better survival (P = 0.06) and showed significantly better disease-free survival (P = 0.02) compared with the RFA group, although differences in liver functional reserve existed. The advantage of hepatic resection was more evident for patients with single tumors and patients with grade A liver damage. In contrast, patients with multinodular tumors survived longer when treated with RFA, regardless of the grade of liver damage. Further analysis showed that surgical RFA could potentially have survival benefits similar to those of hepatic resection for single tumors, and that surgical RFA had the highest efficacy for treating multinodular tumors. Conclusions  In patients with small HCCs within the Milan criteria, hepatic resection should still be employed for those patients with a single tumor and well-preserved liver function. RFA should be chosen for patients with an unresectable single tumor or those with multinodular tumors, regardless of the grade of liver damage. In order to increase long-term oncological control, surgical RFA seems preferable to percutaneous RFA, if the patient’s condition allows them to tolerate surgery.