Biomedical subjects

Masaya Mukai

Publications and source records attributed to Masaya Mukai.

At least 19 recordsLinked to original sources

PubMed2006

Hypogammaglobulinemia with a selective delayed recovery in memory B cells and an impaired isotype expression after rituximab administration as an adjuvant to autologous stem cell transplantation for non-Hodgkin lymphoma.

OBJECTIVES: Some studies have indicated patients who received rituximab as adjuvant to stem cell transplantation had an increased risk of developing severe hypogammaglobulinemia. The mechanism of this hypogammaglobulinemia is unknown, although investigators have hypothesized a further delay in the B-cell recovery as one potential etiology. The aim of this study is to clarify the mechanism(s) of this hypogammaglobulinemia. METHODS: A total of 14 patients with high-risk CD20+ lymphoma underwent an autologous peripheral blood stem cell transplantation (APBSCT). After a hematological recovery, rituximab was given weekly for up to four doses as an adjuvant therapy. RESULTS: After a median follow up of 33.5 months, we found six patients (group A) who had hypogammaglobulinemia, while the eight other patients (group B) had normal serum immunoglobulin levels. A phenotypical analysis revealed that group A patients had already achieved B-cell recovery. However, we found a severe delay in the recovery of CD27+ memory B cells, especially in the IgD-/CD27+ switched populations in group A, but CD27 negative naive B-cells reverted to a normal range in both groups. Consistent with this, reverse transcriptase-polymerase chain reaction studies with peripheral blood mononuclear cells revealed that most patients in group A lacked more than two classes of isotype transcripts. CONCLUSIONS: Abnormal repertoires and impaired isotype expression are seen in patients with common variable immunodeficiency, these data suggested that rituximab after APBSCT can affect not only the B-cell quantities, but also the recovery of the B-cell repertoires.

Adult↗

PubMed2006

[Systemic lupus erythematosus and nucleosome].

The property of nucleosome in systemic lupus erythematosus (SLE) is reviewed. Nucleosome, complex of histone and DNA, is thought to have a pivotal role in pathogenesis of SLE. It is formed during apoptosis that is increased in peripheral lymphocytes of SLE. The concentration of nucleosome is elevated in SLE, probably related with disease activity. Nucleosome is speculated that the clearance from peripheral blood is decreased and that is modified by viral infection to become more immunogenic. Anti-nucleosome antibody is highly positive in majority of SLE, and is very specific for SLE except scleroderma and mixed connective tissue disease. This antibody is thought as a diagnostic marker and probably an activity marker for SLE. Anti-nucleosome antibody forms immune complex with nucleosome. As histone has strong positive charge, it is demonstrated that this nucleosome/anti-nucleosome complex is bound to negatively charged heparan sulfate of glomerular basement membrane in kidney. Then, complements bind to this antibody to generate lupus glomerulonephritis. Although main site of apoptosis in SLE is considered as lymphocytes, we experienced a case with SLE who had liver dysfunction with elevated soluble Fas ligand (sFasL) and apoptosis in her hepatocytes in the active stage of SLE. We measured serum sFasL, and found the relation of sFasL and liver involvement in active SLE. As major source of nucleosome should be apoptosis of lymphocytes in SLE, hepatocytes could be another candidate of apoptosis in some SLE.

Antibodies, Antinuclear↗

PubMed2006

[A case of thrombotic thrombocytopenic purpura with systemic lupus erythematosus].

We described a case of thrombotic thrombocytopenic purpura (TTP) with systemic lupus erythematosus (SLE). A-60-year old woman was admitted to our hospital because of fever, disconsciousness, and general fatigue. 32 years ago, she was diagnosed as SLE with Raynaud's phenomenon, rash, photosensitivity, arthritis, lymphocytopenia, and ANA. Her SLE was well controlled with 10 mg predonisolone as a maintance dose until several weeks ago. On admission, severe thrombocytopenia (0.7x10(4)/microl) and other laboratory data revealed microangiopathic hemolytic anemia and renal dysfunction, Immediately after diagnosed as TTP, plasma exchange and corticosteroid therapy started. In spite of the treatment, disconsciousness progressed and systemic convulsion occurred and died 4 days after admission. Autopsied examination revealed diffuse microvascular hyalinized thrombi in heart, kidney, liver, spleen, and pancreas. Some microvascular thrombi were detected in lymph nodes, bone marrow, intestine. Pathological diagnosis of TTP was made on microvascular hyalinized platelet thrombi in organs. Von Willebrand factor-cleaving protease (VWF-CP) activity in plasma on set is less than 0.5 percent of normal and inhibitor for VWF-CP was detected. We here report a valuable case for analysis of pathogenesis in SLE-TTP.

ADAM Proteins↗

PubMed2006

Predicting recurrence and metastasis of primary esophageal cancer with or without lymph node metastasis.

We studied 42 patients, consisting of 11 stage I/II patients who were node-negative (LN-) and 31 stage II/III patients who were node-positive (LN+). In the LN- patients, detection of occult neoplastic cells (ONCs) in lymph nodes had a sensitivity of 0.0% (0/5), a false-positive (FP) rate of 33.3% (2/6), a specificity of 66.7% (4/6), a false-negative (FN) rate of 100% (5/5), a positive predictive value (PPV) of 0.0% (0/2), and a negative predictive value (NPV) of 44.4% (4/9). In the LN+ patients, the sensitivity of ONCs was 25.0% (5/20), FP rate was 36.4% (4/11), specificity was 63.6% (7/11), FN rate was 75.0% (15/20), PPV was 55.6% (5/9), and NPV was 31.8% (7/22). In LN- patients, positivity for at least 2 of the 3 high-risk criteria had a sensitivity of 20.0% (1/5), FP rate of 16.7% (1/6), specificity of 83.3% (5/6), FN rate of 80.0% (4/5), PPV of 50.0% (1/2), and NPV of 55.6% (5/9). In LN+ patients, these criteria had a sensitivity of 75.0% (15/20), FP rate of 9.1% (1/11), specificity of 90.9% (10/11), FN rate of 25.0% (5/20), PPV of 93.8% (15/16), and NPV of 66.7% (10/15). These results suggest that the high-risk criteria may be useful for predicting recurrence or metastasis in stage II/III lymph node-positive patients with esophageal cancer.

Esophageal Neoplasms↗

PubMed2006

Recurrence and 5-FU sensitivity of stage I/II node-negative breast, lung, or gastric cancer with occult neoplastic cells in lymph node sinuses.

This study was designed to examine the relationship between the presence of occult neoplastic cells (ONCs) in lymph nodes (LNs) and survival in 238 patients with stage I/II LN-negative cancer of the breast, lung, or stomach. In addition, immunohistochemistry for TS and DPD was used to compare the 5-FU sensitivity of the primary tumor in ONC (+) patients. The 5-year relapse-free survival (RFS) rate of 215 ONC (-) patients and 23 ONC (+) patients was 95.2 and 82.6%, respectively (p=0.0107). The 5-year overall survival (OS) rate of the ONC (-) and (+) patients was 97.4 and 77.4%, respectively (p=0.0000). The 6 ONC (+) patients with recurrence showed high and low TS expression in 33.3% (2/6) and 66.7% (4/6), respectively, while high and low DPD expression was observed in 16.7% (1/6) and 83.3% (5/6), respectively. In the 17 ONC (+) patients without recurrence, the corresponding values were 64.7% (11/17), 35.3% (6/17), 29.4% (5/17), and 70.6% (12/17). Patients with a combination of high TS and low DPD expression accounted for 33.3% (2/6) of the ONC (+) patients with recurrence and 52.9% (9/17) of those without recurrence, showing no significant difference between the two groups. These results suggest that ONCs are associated with a lower survival rate and that ONC (+) patients are unlikely to respond to 5-FU+LV therapy.

Antimetabolites, Antineoplastic↗

PubMed2006

Microscopic polyangitis triggered by fungal infection.

We report a case of microscopic polyangitis associated with fungal infection. A 64-year-old man was admitted to our hospital because of renal dysfunction and high fever. He complained of arthralgia and myalgia. He was diagnosed with antineutrophil cytoplasmic antibody-related vasculitis and also had a fungal infection. We treated him with antibiotics including fluconazole. All symptoms disappeared as the infection resolved without the use of steroid therapy. We speculate that the deteriorating vasculitis could have been triggered by overproduction of cytokines in response to the fungal infection.

Antibodies, Antineutrophil Cytoplasmic↗

PubMed2006

Long-term survival and tumor 5-FU sensitivity in patients with stage IV colorectal cancer and peritoneal dissemination.

Among 125 patients with peritoneal dissemination (P1-3) of colorectal cancer, including those with other synchronous metastases, the 5-year overall survival (OS) rate was 13.3% for P1 patients (n=30), 12.8% for P2 patients (n=39), and 1.8% for P3 patients (n=56) (P1 vs. P2, p=N.S.; P2 vs. P3, p=0.02; P1 vs. P3, p=0.001), while the median survival time (MST) was 12.0, 14.1, and 3.1 months, respectively. The 5-year OS rates for patients who had peritoneal dissemination without other metastases were 17.6% (n=17), 12.5% (n=19), and 3.4% (n=28) (P1 vs. P2, p=N.S.; P2 vs. P3, p=N.S.; P1 vs. P3, p=0.039), while the MST was 25.1, 15.1, and 12.5 months, respectively. In the P3 short survival group (SSG; n=13), TS expression was high in 7.7% (1/13) and low in 92.3% (12/13) of tumors, while DPD expression was high in 38.5% (5/13) and low in 61.5% (8/13) of tumors. In the P3 long survival group (LSG; n=15), the corresponding values were 80.0% (12/15), 20.0% (3/15), 33.3% (5/15), and 66.7% (10/15). High TS and low DPD expression was found in only 7.7% (1/13) of the SSG tumors vs. 46.7% (7/15) of the LSG tumors (p=0.028). These results suggest that the prognosis of stage IV colorectal cancer with P3 peritoneal dissemination is extremely poor. In addition, patients fitting the SSG criteria are unlikely to respond to treatment with 5-FU+LV, and may need combination chemotherapy using CPT-11 and/or L-OHP.

Antimetabolites, Antineoplastic↗

PubMed2006

Prospective study on the recurrence/metastasis of stage II/III colorectal cancer and gastric cancer associated with occult neoplastic cells in lymph node sinuses: three-year interim results.

This study was designed to prospectively examine whether the presence of occult neoplastic cells (ONCs) in lymph nodes or positive high-risk (HR) criteria were related to the survival of patients with stage II/III colorectal cancer or gastric cancer. The 3-year relapse-free survival (3Y-RFS) rate was calculated for 79 patients who were registered during a 2-year period. The 3Y-RFS rate was 80.5% in patients without ONCs (n=54) and 84.3% in patients with ONCs (n=25; p=0.9089). Among patients who had stage II/III colorectal cancer, it was 89.0% (n=47) and 76.2% (n=15), respectively (p=0.4131). For patients with stage III colorectal cancer alone, it was 80.8% (n=24) and 62.5% (n=9), respectively (p=0.4006). The 3Y-RFS rate was respectively 88.1% and 77.6% for the HR patients (n=31) and low-risk (LR) patients (n=48) with stage II/III colorectal cancer or gastric cancer (p=0.5545). It was respectively 92.3% and 84.3% for the HR patients (n=20) and LR patients (n=42) with stage II/III colorectal cancer (p=0.5073). Also, the rate was respectively 80% and 76.2% for the HR patients (n=7) and LR patients (n=26) with stage III colorectal cancer alone (p=0.9506). These results indicate that the 3Y-RFS rate is lower in ONC-positive patients with stage II/III colorectal cancer, suggesting that ONCs may have an influence on survival.

Colorectal Neoplasms↗

PubMed2006

Increased S100A4 expression combined with decreased E-cadherin expression predicts a poor outcome of patients with pancreatic cancer.

The calcium-binding protein, S100A4, with an inverse association of E-cadherin, is known to correlate with prognosis in various cancers. In this study, we investigated the expression of the S100A4 and E-cadherin status in relation to the clinicopathological parameters of pancreatic cancer. The expression status of these two proteins was examined in 72 specimens of primary pancreatic carcinoma with immunohistochemistry. Fifty-six of 72 (78%) surgical specimens of primary pancreatic cancer were positive for S100A4 according to immunohistochemistry. Thirty-one (43%) specimens of pancreatic cancer showed positive expression of E-cadherin. The inverse association of S100A4 and E-cadherin expression was significant in the cancers (p < 0.0001). The S100A4 expression correlated significantly with the pathological T stage and poorer prognosis (p = 0.024). The 41 E-cadherin-negative cases showed poorer prognoses and a higher incidence of liver metastasis (p = 0.0344, p = 0.027). The 10 cases with S100A4-negative/E-cadherin-positive cancers showed a significantly better prognosis than the others (p < 0.05). The histological grade (p = 0.004), nodal status (p < 0.0001) and S100A4-positive status (p = 0.048) were highly significant independent prognostic predictors (p < 0.05). These results suggest that S100A4 overexpression combined with reduced E-cadherin expression play important roles in tumor progression and metastasis in pancreatic cancer. The combined examination of these two molecules is useful in evaluating the outcome of pancreatic cancer patient.

Aged↗

PubMed2006

Pyoderma gangrenosum complicated with myelodysplastic syndrome followed by rapidly progressing pyothorax-associated lymphoma: a case report.

This report describes a patient with pyoderma gangrenosum (PG) complicated with myelodysplastic syndrome (MDS) followed by rapidly progressing pyothorax-associated lymphoma (PAL). A 74-year-old man was admitted with cutaneous gangrene associated with MDS. We diagnosed him as having PG, and high-dose oral prednisolone was started. Two months after admission he developed lymphoma rapidly. The patient died in spite of radiation therapy. On autopsy, the pathological diagnosis was diffuse large cell lymphoma. Epstein-Barr virus (EBV)-encoded RNA, and EBV-encoded nuclear antigen (EBNA) were detected in lymphoma cells. This case suggested that immunosuppressive therapy might favour the clonal proliferation of EBV-infected cells.

Aged↗

PubMed2006

Alternating hepatic arterial infusion and systemic chemotherapy for stage IV colorectal cancer with synchronous liver metastasis.

Among 41 patients with synchronous liver metastases of colorectal cancer, 15 patients underwent synchronous resection of their liver metastases and achieved a median survival time (MST) of 1,441 days (versus 748 days for the 26 patients without resection, p=0.038), a median relapse-free survival time of 652 days (MST not reached), and a recurrence rate in the residual liver of 20% (3/15 patients). The alternating hepatic arterial infusion and systemic chemotherapy showed partial response (PR) in 6 cases, stable disease (SD) in 8 cases, and progressive disease (PD) in 1 case (n=15/26). They had an objective response rate of 40% (6/15), tumor control rate (>/= SD) of 93.3% (14/15), one-year progression-free survival rate of 35.7%, 50% time to progression of 270 days, one-year survival rate of 76.2%, and two-year survival rate of 50.8% (MST not reached). Grade 3 leucopenia was observed in 2/15 patients (13.3%). These results suggest that the present alternating therapy may become a standard regimen for patients in whom synchronous resection of liver metastases is impossible and patients who have stage IV colorectal cancer with a risk of recurrence in the remnant liver and/or at extrahepatic sites such as the lungs.

Antineoplastic Agents↗

PubMed2005

Tc-99m MDP bone scintigraphy of myositis as a manifestation of chronic graft-versus-host disease after non-myeloablative peripheral stem cell transplantation.

A 27-year-old man developed polymyositis as a manifestation of chronic graft-versus-host disease (GVHD) after non-myeloablative peripheral blood stem cell transplantation (PBSCT). Bone scintigraphy showed intense, striped, and heterogeneous accumulation of Tc-99m methylene diphosphonate (MDP) in the soft-tissue of his lower limbs, while faint activities were seen in the right upper limb. Tc-99m MDP scintigraphy was very useful for accurate and objective evaluation of the severity of the muscle injury and the extent of polymyositis caused by chronic GVHD.

Adult↗

PubMed2005

Rheumatoid arthritis complicated with myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA)-associated vasculitis: a case report.

This article describes a patient with rheumatoid arthritis (RA) with crescentic glomerulonephritis (CrGN) associated with myeloperoxidase-antineutrophil cytoplasmic antibodies (MPO-ANCA), who responded well to methotrexate (MTX). A 48-year-old woman with a 4-year history of RA was admitted with fever and elevated C-reactive protein. On laboratory evaluation, her level of MPO-ANCA was 422 EU, and urinalysis revealed proteinuria and hematuria. Because she was also suffering from episcleritis, vasculitis was considered. A renal biopsy was performed, which revealed necrotizing CrGN. We diagnosed RA complicated with MPO-ANCA-associated vasculitis. We considered treatment with high-dose oral prednisolone for vasculitis, but the patient refused this treatment. We started MTX at a dose of 8 mg/week for RA from the time of admission, and the patient responded immediately. Biochemical parameters, including C-reactive protein, erythrocyte sedimentation rate, rheumatoid factor, and MPO-ANCA, improved. Seven months later, MPO-ANCA had decreased to 46 EU. In clinical studies, few patients have been reported with RA complicated with ANCA-associated CrGN. This case differs from previous cases in the treatment given. No high-dose steroid with intensive immunosuppression or plasma exchange was required.

Journal Article↗

PubMed2005

Association of neuroendocrine differentiation with neoadjuvant hormone therapy effects in prostatic cancer.

Histological therapeutic effects of neoadjuvant hormone therapy (NHT) in prostatic cancer were examined, focusing on the association with neuroendocrine differentiation (NED), using 69 radical prostatectomy cases. The effects of NHT were classified into 3 grades based on the extent of tumor degeneration as observed with hematoxylin and eosin staining. NED cells in the cancer were semi-quantified into 4 grades (negative, 1+, 2+, and 3+) by immunohistochemical staining of chromogranin A (CgA). According to the therapeutic effects, the cases are divided as follows: good response in 26 patients, intermediate in 20, poor in 23. The histological therapeutic effects were significantly weaker in the CgA-positive group than the CgA-negative group (p=0.02). A close relationship between the extent of CgA expression and the histological response was also demonstrated (p=0.007). In the biopsy specimens before NHT, CgA was positive in 46% (32/69) and there was no significant difference in histological therapeutic effects between the positive and negative groups. However, the therapeutic effects were significantly weaker in 22 CgA-positive cases for both biopsy and prostatectomy specimens than in 18 CgA-negative cases for both specimens (p=0.001). In conclusion, although it seems difficult to predict the therapeutic effects of NHT using the biopsy specimens of prostatic cancer, we believe that NED is negatively associated with histological response of prostatic cancer to NHT.

Adenocarcinoma↗

PubMed2005

Occult neoplastic cells and malignant micro-aggregates in lymph node sinuses: review and hypothesis.

Many studies have shown a close relationship between the detection of occult neoplastic cells (ONCs) freely floating in lymph node sinuses remote from the primary tumor and the recurrence/metastasis of various malignancies. If 5 to 10 circulating ONCs form an aggregate of tumor cells, it may easily escape attack by the host immune system. Since such malignant micro-aggregates cannot pass through the circulation in the liver and lungs, which filter tumor cells from the blood, the aggregates may become anchored in these organs and cause metastasis. A hypothesis is proposed that the most important factor leading to distant metastasis/recurrence of stage I or II cancer without microscopic lymph node metastasis, so-called N0 local disease (N0-LD), is the release of malignant micro-aggregates consisting of many ONCs from the primary tumor. Distant metastasis/recurrence of N0-LD may occur when such infiltrating/proliferating cells enter target organs, especially the liver and lungs, in a viable state during their first pass through the circulation preoperatively and/or intraoperatively.

Humans↗

PubMed2005

Clinical usefulness of serum and immunohistochemical markers in patients with stage Ia and Ic ovarian cancer.

We compared the preoperative serum tumor marker values and diameters of ovarian tumors between 14 stage Ia ovarian cancer patients with a good prognosis and 14 stage Ic patients with a poor prognosis. The aim was to examine the usability of tumor markers and diameter of ovarian tumors for prognostic diagnosis of clinically advanced phases. In occult neoplastic cells (ONCs), a tumor marker indicative of recurrence and metastasis, the cytokeratin-positive cells in lymph node biopsies, were also compared. In a preoperative comparison of serum tumor markers, CA125 levels in stage Ia and Ic patients were 47.1+/-15.9 (median, 31.9 U/ml) and 370.6+/-146.2 U/ml (median, 135.6 U/ml), respectively (p=0.0457), and CA19-9 levels were 25.5+/-5.5 (median, 20.4 U/ml) and 564.5+/-192.4 U/ml (median, 248.0 U/ml), respectively (p=0.0131). In a comparison of tumor diameters during surgery, diameters of stage Ia and Ic patients were 117.3+/-11.4 (median, 100.0 mm) and 182.0+/-29.2 mm (median, 145.0 mm), respectively (p=0.0457). ONCs were not detected in any stage Ia patients, but detected in 3 (30%) stage Ic patients. In conclusion, clinical progression was evaluated using CA125 and CA19-9 serum markers and tumor diameters in stage Ia and Ic patients, and demonstrated significant differences between stage. ONCs were only detected in the lymph nodes of stage Ic patients.

Adult↗

PubMed2005

Successful treatment of renal cell carcinoma with mediastinal lymph node metastasis by interleukin-2: a case report.

A 57-year-old woman presented to our hospital with macrohematuria. Renal cell carcinoma (RCC) of the left kidney with bilateral pulmonary and mediastinal lymph node metastases was diagnosed. Radical nephrectomy was performed. Pathological examination confirmed the diagnosis of RCC (pT2pN0M1), so immunotherapy was performed using interleukin-2 (IL-2). The mediastinal lymph node metastases disappeared completely after 5 months of immunotherapy. Investigation of immunological parameters showed an increase of CD8-positive T cells (CD8) and a decrease of CD14-positive cells (CD14), leading to a marked increase of the CD8/CD14 ratio. Although her pulmonary metastases are unchanged, the mediastinal metastases still show complete remission at 14 months postoperatively. The CD8/CD14 ratio may have potential as a new marker for monitoring the response of RCC to immunotherapy and selecting suitable patients for such therapy.

Carcinoma, Renal Cell↗

PubMed2005

Recurrence and 5-FU sensitivity of stage III/Dukes' C colorectal cancer with occult neoplastic cells in lymph node sinuses.

In 72 patients without occult neoplastic cells (ONCs) in their lymph node sinuses, the 5-year relapse-free survival (RFS) rate and overall survival (OS) rate were 71.3% and 69.2%, respectively. In 33 patients with ONCs, the 5-year RFS rate and OS rate were 33.9% and 31.3%, respectively. There was a marked difference of survival between the two groups (p=0.0001 and p=0.0003). The metastatic lymph nodes of the 33 ONC-positive patients had high and low levels of thymidilate synthase (TS) expression in 38.1% (8/21) and 61.9% (13/21) of the recurrence group (n=21), respectively, while high and low levels of dihydropyrimidine dehydrogenase (DPD) expression were found in 38.1% (8/21) and 61.9% (13/21), respectively. In the non-recurrence group (n=12), high and low levels of TS or DPD expression were detected in 58.3% (7/12) and 41.7% (5/12) versus 16.7% (2/12) and 83.3% (10/12), respectively. Patients with high TS and low DPD expression accounted for 9.5% (2/21) of the recurrence group and 50.0% (6/12) of the non-recurrence group (p<0.01). These results suggest that ONCs are clearly associated with the 5-year RFS and OS rates. Unlike the non-recurrence group, the recurrence group of ONC-positive patients with Dukes' C colorectal cancer is unlikely to respond well to treatment with 5-FU plus LV and require combination chemotherapy based on CPT-11 and/or L-OHP.

Antineoplastic Combined Chemotherapy Protocols↗