Clinical characteristics of cytomegalovirus infection in rheumatic diseases: multicentre survey in a large patient population.

OBJECTIVE: To survey and elucidate the clinical characteristics of CMV infection in rheumatic disease patients. METHODS: A detailed questionnaire survey on CMV infection was carried out against rheumatic disease patients hospitalized in member hospitals, and the obtained clinical and/or laboratory data were analysed. RESULTS: Out of 7377 patients, 151 were diagnosed as having CMV infection. The underlying diseases ranged broadly, but SLE, microscopic polyangiitis, and dermatomyositis were the most common. Four were diagnosed histopathologically, and the others via positive CMV antigenaemia. In addition to oral corticosteroid for all but one patient, 81 were treated with pulsed methylprednisolone (MPSL), 64 with cyclophosphamide (CYC) and 36 with other immunosuppressants. Forty-four had a fatal outcome, for which presence of clinical symptoms, other infectious complications, lymphopenia, an older age (>59.3 yrs) and the use of pulsed MPSL were significant risk factors (P < 0.05) by univariate analysis. Multivariate analysis retained the first three (P < 0.05). The CMV antigenaemia count was significantly higher for the symptomatic than asymptomatic [10.1 (0.0-2998.0) vs 4.0 (1.3-1144.4)/10(5) PMNs, respectively, P < 0.05; threshold count: 5.6/10(5) PMNs]. No treatment benefit by anti-viral agent was observed as for survival. CONCLUSION: CMV infection was mostly diagnosed by antigenaemia, and occurred among patients under strong immunosuppressive therapy using pulsed MPSL and/or immunosuppressants. Lymphopenia, presence of symptoms and other infections are significant risk factors for a poor outcome and pulsed MPSL and an older age may predict it. Patients were prone to be symptomatic with anti-genaemia count over 5.6/10(5) PMNs.

Postmarketing surveillance of the safety profile of infliximab in 5000 Japanese patients with rheumatoid arthritis.

OBJECTIVES: A large-scale postmarketing surveillance (PMS) study was carried out to determine the safety profile of infliximab in Japanese patients with rheumatoid arthritis (RA). METHODS: The PMS study was performed for all patients with RA who were treated with infliximab. They were consecutively registered in the PMS study at the initiation of infliximab treatment and were prospectively monitored with all adverse events noted for a period of 6 months. All case reports, which include safety-related events, were collected monthly. RESULTS: Adverse drug reactions (ADRs) were assessed for 6 months in 5000 patients who were consecutively enrolled in the PMS study. The incidence rates of total and serious ADRs were 28.0% and 6.2%, respectively. "Infections" or "respiratory disorders" were most commonly observed among serious ADRs. Bacterial pneumonia developed in 2.2%, tuberculosis in 0.3%, suspected Pneumocystis jiroveci pneumonia (PCP) in 0.4% and interstitial pneumonitis in 0.5%. Bacterial pneumonia (for which individuals of male gender, of older age and those with advanced rheumatoid arthritis and comorbid respiratory disease were most at risk) began to develop immediately after the start of treatment, while tuberculosis, PCP and interstitial pneumonitis developed about 1 month later. Serious infusion reactions were observed in 0.5% and were more likely to occur in patients who had participated in previous clinical trials of infliximab. CONCLUSION: This postmarketing surveillance study of patients treated with infliximab showed that infliximab in combination with low-dose MTX was well tolerated in Japanese patients with active RA.

Minilaparotomy approach for colonic cancer: initial experience of 54 cases.

BACKGROUND: The early outcomes of minilaparotomy for resection of colonic cancer were evaluated. METHODS: In this study, 54 patients (34 Dukes' A, 15 Dukes' B, and 5 Dukes' C) successfully underwent curative resection of colonic cancer via minilaparotomy (skin incision, > or = 7 cm). The major exclusion criteria for this approach required a body mass index greater than 25 kg/m2, a tumor size exceeding 7 cm, a preoperative ileus, and tumor invading the adjacent organs. Patients (n = 54) who had undergone conventional open surgery before the introduction of this technique served as the control group by matching several clinicopathologic factors including body mass index. RESULTS: The passage of flatus (p < 0.01) and the beginning of oral intake (p = 0.02) were earlier, analgesic requirements were lower (p < 0.01), and postoperative serum C-reactive protein levels were lower in the minilaparotomy group (p < 0.01). The blood loss and frequency of postoperative complications did not differ between the groups. CONCLUSION: A minilaparotomy approach is a feasible, minimally invasive, and attractive alternative to conventional laparotomy for selected patients with colonic cancer.

Gasless laparoscopic surgery for ulcerative colitis and familial adenomatous polyposis:initial experience of 7 cases.

PURPOSE: We evaluated the data on initial experience of gasless laparoscopic surgery for patients with ulcerative colitis (UC) and familial adenomatous polyposis (FAP). PATIENTS AND METHODS: Seven patients (male/female = 3:4, median age 23, UC/FAP=5:2) underwent gasless laparoscopic total (procto) colectomy. Our basic surgical procedure involved (1) a 6- to 8-cm incision made at the beginning of the operation, (2) the wound pulled upward and/or laterally by retractors, and (3) conventional surgical instruments used through the wound; occasionally laparoscopic assistance and abdominal lifting were employed. The results were compared to those of 7 patients who had undergone conventional open surgery. RESULTS: Oral intake started earlier (p = 0.03) and C-reactive protein level on POD 4 was lower (p = 0.03) in the gasless group than in the control group. Duration of surgery, blood loss, requirement of analgesia, and morbidity rate were not significantly different between the groups. CONCLUSION: Our preliminary results suggest that gasless laparoscopic surgery for UC and FAP is feasible and can be an alternative method for minimally invasive surgery.

Incidence of peripheral blood eosinophilia and the threshold eosinophile count for indicating hypereosinophilia-associated diseases.

BACKGROUND: A definite threshold of the peripheral blood eosinophile count that indicates the presence of hypereosinophilia-associated diseases has not yet been determined. METHODS: The threshold eosinophile count at which cases of hypereosinophilia-associated diseases (n = 25) can be differentiated from those of bronchial asthma (n = 101) was determined. Then, the incidences of eosinophile counts greater than 1.0 x 10(9)/l or the threshold level, were studied by analysis of 43,805 samples sent to the laboratory, and the diseases associated with the increased counts were determined. RESULTS: The eosinophile count in cases of hypereosinophilia-associated diseases and in those of bronchial asthma were 10.967 +/- 1.680 x 10(9)/l and 0.574 +/- 0.045 x 10(9)/l, respectively (P < 0.001); the threshold was 2.052 x 10(9)/l. The percentages of samples with an eosinophile count of more than 1.0 x 10(9)/l and 2.052 x 10(9)/l were 0.6% and 0.1%, respectively; the latter comprised of 41 samples from 24 patients including eight with hypereosinophilia-associated diseases. The patients with hypereosinophilia-associated diseases had a significantly higher count, and a higher incidence of counts of more than 2.052 x 10(9)/l, than others, including patients with malignancies and symptoms conventionally referred as "atopic diseases". CONCLUSION: Hypereosinophilia-associated diseases are associated with a very high eosinophile count of more than 2.052 x 10(9)/l, which was observed rarely.

[Effect of peroral doxifluridine plus hepatic arterial infusion for synchronous liver metastasis of colorectal cancer--correlation with the expression of thymidine phosphorylase and dihydropyrimidine dehydrogenase in primary colorectal cancer lesions].

We investigated whether the efficacy of peroral doxifluridine and hepatic arterial 5-FU infusion on synchronous liver metastasis of colorectal cancer could be predicted based on the expression of thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) in the primary colorectal lesions. Ten patients with synchronous liver metastasis of colorectal cancer were given doxifluridine (600-800 mg/body/day) orally and 5-FU (500 mg/body, once or twice a week) through the hepatic artery following resection of the primary lesions between June 1996 and July 2001. The levels of TP and DPD in the primary lesions were determined by an enzyme-linked immunosorbent assay. The level of TP, DPD, and the ratio of TP/DPD in patients with partial response (n = 4) were 89.8 +/- 30.0 U/mg protein, 23.5 +/- 25.7 U/mg protein, and 3.8 +/- 1.4, respectively, while those in patients with no response or progressive disease (n = 6) were 41.8 +/- 9.7 U/mg protein, 25.8 +/- 15.8 U/mg protein, and 2.2 +/- 1.6, showing significant difference (p < 0.01) in the level of TP between the groups. These results indicate that determining the level of TS in primary colorectal lesions may be useful for predicting the efficacy of this regimen for patients with synchronous liver metastasis of colorectal cancer.

[Histological evaluation of liver metastasis of colorectal cancer following hepatic arterial infusion with degradable starch microspheres and adriamycin/mitomycin C].

Little is known about the histological effect of hepatic arterial infusion with degradable starch microspheres (DSM), adriamycin (ADM), and mitomycin C (MMC) on liver metastasis of colorectal cancer. We histologically examined hepatic metastases resected following this therapy and investigated their relation to macroscopic changes in size. Neither a histological nor macroscopic effect was found in 2 patients receiving this therapy only one time. A 57-year-old woman with a solitary liver metastasis who received this therapy repeatedly (five times every 3 to 4 weeks) subsequently showed a partial response. She underwent hepatic metastasectomy 5 months after the end of the therapy. Histological examination showed that the greater part of the metastatic lesion was composed of fibrous tissues without any viable cancer cells. In conclusion, it should be noted that repeated infusions of DSM.ADM.MMC for liver metastases of colorectal cancer can have a marked histological effect even though the lesion does not show a complete response.

[Tumoral levels of thymidine phosphorylase and dihydropyrimidine dehydrogenase in elderly colorectal cancer patients].

Fluoropyrimidine therapy for elderly colorectal cancer patients remains controversial. Tumoral levels of thymidine phosphorylase (TP), dihydropyrimidine dehydrogenase (DPD), and the ratio of TP to DPD determined by an enzyme-linked immunosorbent assay were compared between colorectal cancer patients aged 75 or over (elderly group, n = 25) and those 74 years or less (control group, n = 87), in order to examine the characteristics of colorectal cancers in the elderly from the viewpoint of metabolic and anabolic pathways of fluoropyrimidines. The level of TP was 78.4 +/- 47.0 unit/mg protein in the elderly group and 82.4 +/- 70.9 unit/mg protein in the control group (p = 0.86). The level of DPD was 53.7 +/- 43.1 unit/mg protein in the elderly group and 52.6 +/- 37.7 unit/mg protein in the control group (p = 0.73). The ratio of TP to DPD was 2.0 +/- 1.2 in the elderly group and 1.8 +/- 0.9 in the control group (p = 0.44). These three parameters did not differ between the groups when divided according to Dukes' stage (Dukes' A.B versus Dukes' C.D). These results suggest that there are no age-specific characteristics in relation to conversion of fluoropyrimidines such as capecitabine and doxifluridine to 5-fluorouracil (FU) and degradation of 5-FU in colorectal cancers.

Impact of oral antimicrobial prophylaxis on surgical site infection and methicillin-resistant Staphylococcus aureus infection after elective colorectal surgery. Results of a prospective randomized trial.

The impact of oral antimicrobial prophylaxis on the surgical site infection and methicillin-resistant Staphylococcus aureus (MRSA) infection after elective colorectal surgery was evaluated by a prospective randomized single-blind study. The patients were randomly allocated to receive either mechanical bowel cleansing with polyethylene glycol alone (group 1) or mechanical cleansing plus oral antimicrobial prophylaxis with kanamycin and erythromycin for 2 days prior to surgery (group 2). In both groups, cefotiam was intravenously given twice a day for 3 days. A total of 143 patients (71 for group 1 and 72 for group 2) were eligible. The incidence of a surgical site infection was 23.9% in group 1 and 11.1% in group 2 (P = 0.04). The incidence of MRSA infection including at surgical and remote sites was 11.1% in group 1 and 5.6% in group 2 (P = 0.19). A multivariate logistic regression analysis showed that the risk of surgical site infection was influenced by the choice of the chemical bowel preparation (P = 0.03) and blood loss (P < 0.01), while an MRSA infection was predominantly influenced by blood loss (P < 0.01) followed by coexisting underlying diseases (P = 0.07). These results suggest that preoperative antimicrobial prophylaxis would be useful for reducing the incidence of a surgical site infection without increasing the risk of an MRSA infection following elective colorectal surgery.

[Clinical significance of determinations of dihydropyrimidine dehydrogenase levels in primary and hepatic lesions of colorectal cancer patients].

Dihydropyrimidine dehydrogenase (DPD) levels were determined by enzyme-linked immunosorbent assay in primary tumors and adjacent normal mucosa from 114 colorectal cancer patients, including 9 with synchronous liver metastases. The level of intratumoral DPD was 55.0 +/- 38.7 unit/mg protein (n = 114) and that of mucosal DPD was 55.0 +/- 38.7 unit/mg protein (n = 114). The ratio of intratumoral DPD to mucosal DPD was 1.8 +/- 0.8 in patients developing metachronous liver metastases (n = 7), 1.0 +/- 0.5 in patients without recurrence (n = 61), and 1.0 +/- 1.1 in patients with synchronous liver metastases (n = 31) (p = 0.01, metachronous liver metastasis group versus recurrence-free and synchronous liver metastasis groups). The levels of DPD were higher in primary lesions than in synchronous liver metastasis (n = 9, p < 0.05). These results indicate that: (1) degradation of 5-fluorouracil (5-FU) is enhanced in hepatic lesions more than in primary lesions, which is consistent with previous findings showing the therapeutic advantage of hepatic arterial infusion over intravenous infusion in relation to the treatment of 5-FU for liver metastases of colorectal cancer patients; and (2) predicting the effectiveness of hepatic arterial infusion of 5-FU for patients with metachronous liver metastases is difficult based on DPD determination of primary lesions alone.

[Hepatic arterial injection of degradable starch microspheres (DSM) combined with adriamycin (ADM) and mitomycin C (MMC) in patients with liver metastasis of colorectal cancer].

We evaluated the adverse effects, response rates, and changes in CEA-doubling time before and during DSM.ADM.MMC therapy (DSM therapy) in 8 patients with liver metastases of colorectal cancer. In principle, 600 mg/body DSM, 30 mg/body ADM, and 10 mg/body MMC were injected into the hepatic artery, and this treatment was repeated as often as possible. A total of 26 injections revealed no severe adverse effects. In 5 patients who received 3 or more injections of DSM, the response rate was 20% (partial response, one) and an improvement of CEA-doubling time was confirmed in 3 patients (60%). Two patients who demonstrated the shortening of CEA-doubling time after this therapy had shorter survival. It is suggested that to compare CEA-doubling times before and during DSM therapy is useful for selecting candidates for this treatment.

[Combination chemotherapy with irinotecan hydrochloride plus carboplatin for patients with advanced or recurrent colorectal cancer--a pilot study].

A pilot study was performed to evaluate the feasibility and efficacy of irinotecan hydrochloride (CPT-11) plus carboplatin (CBDCA) for treatment of advanced or recurrent colorectal cancer. Fifteen patients with colorectal cancer (nonresectable, 1; noncurative resection, 5; recurrent disease, 9) were treated with CPT-11 (40-50 mg/m2) plus CBDCA (70-100 mg/m2) once a week for 2-3 weeks followed by a one-week rest. This treatment was repeated until disease progression or severe toxic effects were found. The total dose of CPT-11 ranged from 135 to 1,214 (median, 467) mg/m2 and that of CBDCA ranged from 267 to 2,022 (median, 933) mg/m2. Adverse effects included nausea (grade 2) in 2 (13.3%) diarrhea (grade 2) in 2 (13.3%), leukopenia (grade 3) in 2 (13.3%), thrombocytopenia (grade 1) in one (6.7%), and hair falling (grade 3) in one (6.7%). The response rate of 14 evaluable patients was 14.3% (CR, 1; PR,1; NC,7; PD,5). The median survival time of all patients was 405 days from the start of chemotherapy. The survival time of patients with CR, PR, and NC (n = 9) tended to be longer than that of those with PD (n = 5) (p = 0.06). The median time to disease progression was 105 days. These results suggest that this combination chemotherapy is feasible and effective in the treatment of advanced or recurrent colorectal cancer.

Pachymeningitis in microscopic polyangiitis (MPA): a case report and a review of central nervous system involvement in MPA.

A case of microscopic polyangiitis (MPA) with pachymeningitis is described. The patient had renal, skin, gallbladder and peripheral nervous system involvement, simultaneously with pachymeningitis. Necrotizing glomerulonephritis with crescent formation, and necrotizing small vessel vasculitis in the kidney and skin were confirmed by biopsy. A highly elevated titer of antineutrophil cytoplasmic antibody for myeloperoxidase (MPO-ANCA) was observed. All of the clinical and laboratory abnormalities improved with high-dose pulse and conventional steroid therapy. The literature on central nervous system involvement in MPA and perinuclear-ANCA (p-ANCA)-related vasculitis is reviewed. This case serves to emphasize that pachymeningitis can occur as one of the features of MPA.

Pneumomediastinum in dermatomyositis: association with cutaneous vasculopathy.

OBJECTIVES: To study the pathogenesis of pneumomediastinum in polymyositis/dermatomyositis (PM/DM). PATIENTS AND METHODS: The clinical records of 48 patients with PM/DM were reviewed, focusing mainly on the presence of pneumomediastinum and cutaneous vasculopathy, and the chest radiographic changes. A patient with pneumomediastinum with a characteristic change in his bronchus is described in detail. Case reports of pneumomediastinum in PM/DM in English publications are reviewed. RESULTS: Among the 48 patients with PM/DM, pneumomediastinum was observed as a complication in four patients with DM and none of the patients with PM. Three of the four patients with pneumomediastinum, but only six of the 44 patients without this complication, had associated cutaneous vasculopathy. There was a significant association of pneumomediastinum with cutaneous vasculopathy (p = 0.02) and younger age (p = 0.04), but not with the prevalence of lung disease. A 30 year old man (patient 1) with DM, who had interstitial pneumonitis and skin ulceration due to vasculopathy, developed pneumomediastinum. Fibreoptic bronchoscopy showed white plaques on the bronchial mucosa, which were confirmed by microscopic examination as representing subepithelial necrosis. A literature review showed 13 cases of DM but no patient with PM with pneumomediastinum. CONCLUSIONS: In patient 1, bronchial necrosis due to vasculopathy was strongly suspected as being responsible for the pneumomediastinum. The results suggest that pneumomediastinum was associated not with interstitial pneumonitis but with the complication of vasculopathy appearing as skin lesions in DM.

Clinical significance of ventilation/perfusion scans in collagen disease patients.

UNLABELLED: The purpose of this study was to detect disturbances in pulmonary circulation in collagen disease patients by means of a non-invasive technique. METHODS: Ventilation/perfusion scans with 133Xe gas and 99mTc-macroaggregated albumin (MAA) were performed in 109 patients with various collagen diseases. Functional images of V, Vol, Q and V/Q ratio were obtained at total lung capacity. Wash-out time was calculated from the wash-out curve. Whole body scans were performed in 65 patients to evaluate intra-pulmonary shunts. RESULTS: Increased V/Q areas were observed in 74 patients (67.9%), suggesting some impairment of pulmonary perfusion. Decreased perfusion, probably due to vasculitis or intravascular microcoagulation, was observed often, even in patients without pulmonary fibrosis. Shunt ratios over 10% were observed in 8 of the 65 patients (12.3%), indicating formation of PA-PV shunts secondary to peripheral vascular impairment. Wash-out time was prolonged in 37 patients (33.9%), shortened in 18 (16.5%), and within the normal range in 54 (49.6%). The prolonged and normal wash-out times in the patients with pulmonary fibrosis may represent obstructive changes in the small airways superimposed on the fibrosis. CONCLUSION: Ventilation/perfusion scans are a very useful tool for evaluating collagen lung diseases, and they might contribute to treatment decisions for the patients.