Primary solitary fibrous tumour of the prostate: A case report and literature review.

INTRODUCTION: Solitary fibrous tumour (SFT) is a rare mesenchymal tumour with intermediate malignant potential. Although this tumour arises in several sites, prostatic SFT is an extremely rare neoplasm and may prove confusing owing to the lack of clinical experience because of tumour rarity. The diagnosis may be further difficult because SFTs can manifest positive immunoreactivity for CD34 and progesterone receptor, which are known markers of prostatic stromal tumours. Herein, we describe a case of prostatic SFT that was difficult to differentiate from a prostatic stromal tumour of uncertain malignant potential because of positive immunoreactivity to CD34 and progesterone receptor. CASE REPORT: A 40-year-old Japanese man presented with lower abdominal pain. Computed tomography revealed a prostatic mass; furthermore, prostate core needle biopsy revealed proliferating bland spindle cells, without necrosis or prominent mitoses. Tumour cells were positive for CD34 and progesterone receptor on immunohistochemical analysis; thus, a prostatic stromal tumour of uncertain malignant potential was initially suspected. However, as the tumour cells showed positive immunoreactivity for STAT6, the final diagnosis was an SFT of the prostate. The patient underwent tumour resection, and at the 6-month postoperative follow-up, neither local recurrence nor distant metastasis occurred. CONCLUSION: For an accurate diagnosis of an SFT of the prostate, STAT6 immunohistochemistry should be conducted for all mesenchymal tumours of the prostate. When STAT6 immunohistochemical analysis is unfeasible, pathologists should be aware that the morphological and immunohistochemical characteristics of SFT variable from case to case and diagnose with combined analysis of several immunohistochemical markers.

Validation of the distress and impact thermometer and the changes of mood during the first 6 months of treatment in gynecological cancer patients: a Kansai Clinical Oncology Group (KCOG)-G1103 prospective study.

PURPOSE: To verify distress and impact thermometer (DIT) for screening emotional distress in gynecological cancer patients by Hospital Anxiety and Depression Scale total (HADS-T) as gold standard and to assess emotional changes by DIT and HADS-T. METHODS: A prospective study was conducted in newly diagnosed gynecological cancer patients during the peri-treatment period after the cancer diagnosis followed by 6-month. We defined a HADS-T score of ≥11 as being indicative of emotional distress. RESULTS: 117 patients were enrolled between May 1, 2011 and March 31, 2012, and 95 were eligible. The median age was 54 years (range 31-77). (1) From the baseline to 3-month, distress (DIT-D) ≥4 with Impact (DIT-I) ≥2 exhibited sensitivity, specificity, positive predictive value (PPV), and negative predictive values (NPV) of 0.776 [95 % confidential interval (CI) 0.688, 0.850], 0.889 (95 % CI 0.824, 0.954), 0.868 (95 % CI 0.792, 0.949), and 0.808 (95 % CI 0.731, 0.886), respectively. (2) At 6-month, DIT-D ≥2 with DIT-I ≥1 exhibited sensitivity, specificity, PPV and NPV of 0.893 (95 % CI 0.778, 1), 0.825 (95 % CI 0.707, 0.942), 0.781 (95 % CI 0.638, 0.928), and 0.917 (95 % CI 0.826, 1). (3) At 6-month, the HADS-T, DIT-D, and DIT-I scores in individual patients were significantly reduced by a mean of 4.57 (p < 0.0001), 2.34 (p < 0.0001), and 1.10 (p = 0.0031), respectively, compared with those scores of baseline (Student's paired t test), but still remained high. CONCLUSIONS: (1) On acute phase within 3-month setting, DIT; DIT-D ≥4 with DIT-I ≥2, is a reliable cut-off to screen emotional distress among gynecological cancer patients. (2) The patients' moods had improved, but not completely recovered at 6-month after the diagnosis.

Feasibility and efficacy of intraperitoneal docetaxel administration as salvage chemotherapy for malignant gynaecological ascites.

Ovarian and endometrial cancers diagnosed at advanced stages are often associated with malignant ascites. This study aimed to determine the safety, feasibility and efficacy of intraperitoneal (IP) docetaxel (TXT) for the treatment of ascites. A phase I study, including nine patients, was undertaken to determine the maximum tolerable dose. Efficacy was retrospectively assessed in 18 patients treated with 40-70 mg/m(2) IP TXT between 2005 and 2012. In a phase I study, the dose was safely escalated to a maximum of 70 mg/m(2), at which level no patients had grade -3 haematological adverse events. In a retrospective study of 18 patients, seven had an Eastern Cooperative Oncology Group performance status of 3; 16 had prior paclitaxel administration and two, with doses of 40 and 70 mg/m(2), experienced a serological response and a decrease in paracentesis. Thus, palliative treatment of recurrent OC should be further studied with 40 mg/m(2) among more patients, and 70 mg/m(2) could be evaluated for first-line IP chemotherapy.

Global histone modification of H3K27 correlates with the outcomes in patients with metachronous liver metastasis of colorectal cancer.

BACKGROUND: We evaluated the methylation patterns of histone H3 lysine 27 (H3K27), H3 lysine 36 (H3K36) and the expression of H3K27 methylase EZH2 in patients with colorectal carcinomas with metachronous liver metastasis to search for biomarkers identifying these patients. METHODS: Double 2-mm core tissue microarrays were made from 54 paraffin-embedded samples of primary colorectal adenocarcinomas and corresponding liver metastases and examined using an immunohistochemical analysis of dimethylation and trimethylation in H3K27, H3K36 and EZH2. Positive tumor cell staining for each histone modification (H-score) was used to classify patients into low- and high-staining groups, which were then examined to identify any correlations between the clinicopathological parameters and the clinical outcomes. RESULTS: The H-scores of H3K27me2 were lower in the liver metastases than in the corresponding primary tumors, while the H-scores of H3K36me2 were higher in the liver metastases than in the corresponding primary tumors (P < 0.001). H3K27me2 in the primary tumors correlated with tumor size (P = 0.016), H3K36me2 in the primary tumors correlated with histological type (P = 0.038), and H3K36me3 in the primary tumors correlated with lymph node metastasis (P = 0.017). In addition, lower levels of H3K27me2 in the primary tumors correlated with poorer survival rates (P = 0.039). The multivariate survival analysis showed that the H3K27me2 status is an independent prognostic factor for colorectal cancer patients (P = 0.047). CONCLUSIONS: Our findings suggest that the methylation level of H3K27me2 detected with immunohistochemistry may be an independent prognostic factor for metachronous liver metastasis of colorectal carcinomas.

KRAS and BRAF mutations are rare and related to DNA mismatch repair deficiency in gastric cancer from the East and the West: results from a large international multicentre study.

BACKGROUND: Inhibitors of the epidermal growth factor (EGFR) signaling pathway have a major role in the treatment of KRAS wild-type colorectal cancer patients. The EGFR pathway has been shown to be activated in gastric cancer (GC). However, published data on KRAS and BRAF mutation status is limited in GC and has not been compared between GC from different geographic regions. METHODS: The prevalence of KRAS and BRAF mutations was established in 712 GC: 278 GC from the United Kingdom, 230 GC from Japan and 204 GC from Singapore. The relationship between KRAS/BRAF mutation status, DNA mismatch repair (MMR) status, clinicopathological variables and overall survival was analysed. RESULTS: Overall, 30 (4.2%) GC carried a KRAS mutation. In total, 5.8% of the UK GC, 4% of Japan GC and 1.5% of Singapore GC were KRAS mutant. KRAS mutant GC had fewer lymph node metastases in the UK cohort (P=0.005) and were more frequent in elderly patients in the Japan cohort (P=0.034). KRAS mutations were more frequent in MMR-deficient GC in the UK and the Japanese cohort (P<0.05). A BRAF mutation was only detected in a single Japanese GC. CONCLUSIONS: This large multicentre study demonstrated that KRAS mutations and DNA MMR deficiency have a role in a small subgroup of GC irrespective of country of origin, suggesting that this subgroup of GC may have developed along a common pathway. Further studies need to establish whether concomitant mutations or amplifications of other EGFR signalling pathway genes may contribute to the activation of this pathway in GC.

The cellular level of histone H3 lysine 4 dimethylation correlates with response to adjuvant gemcitabine in Japanese pancreatic cancer patients treated with surgery.

BACKGROUND: To search for biomarkers identifying pancreatic cancer patients likely to benefit from adjuvant gemcitabine chemotherapy, we investigated the status of several histone modifications in pancreatic tumors and their relationship to clinicopathological features and outcomes. METHODS: Sixty one pancreatic cancer patients, primarily treated by surgical removal of tumors, were involved in the study. Thirty patients completed postoperative adjuvant gemcitabine, and in 31 it was discontinued. Tumor specimens were examined using immunohistochemistry for di- and tri-methylation of histone H3 lysine 4 (H3K4me2 and H3K4me3), dimethylation and acetylation of histone H3 lysine 9 (H3K9me2 and H3K9ac), and acetylation of histone H3 lysine 18 (H3K18ac). Positive tumor staining for each histone modification was used to classify patients into low- and high-staining groups, which were examined for relationships to clinicopathological features and clinical outcomes. RESULTS: High expression of H3K4me3 was related to the well and moderately differentiated tumor histological type (p = 0.012) and low expression of H3K4me2 was related to the presence of perineural invasion (p = 0.007). No cellular histone modifications were associated with overall or disease-free survival of patients as a whole. In the subgroup analyses, a low level of H3K4me2 was significantly associated with worse disease free survival in patients that completed adjuvant gemcitabine (p = 0.0239). Univariate and multivariate hazard models also indicated that a low level of H3K4me2 was a significant independent predictor of disease-free survival (p = 0.007). CONCLUSION: H3K4me2 was found to be a predictor of response to adjuvant gemcitabine in Asian patients with pancreatic cancer.

Secretion of intelectin-1 from malignant pleural mesothelioma into pleural effusion.

BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare but fatal tumour. Although most MPM patients show pleural effusion at even the early stage, it is hard to diagnose as MPM at the early stage because a sensitive and reliable diagnostic marker for MPM has not been found in plasma or pleural effusion. METHODS: In this study, we investigated whether intelectin-1 was specifically contained in MPM cells and the pleural effusion of MPM patient by immunohistochemistry, western blotting, and enzyme-linked immunosorbent assay. RESULTS: Malignant pleural mesothelioma cell lines, but not lung adenocarcinoma cell lines, secreted intelectin-1. In immunohistochemistry, epithelioid-type MPMs, but neither pleura-invading lung adenocarcinomas nor reactive mesothelial cells near the lung adenocarcinomas, were stained with anti-intelectin antibodies. Pleural effusion of MPM patients contained a higher concentration of intelectin-1 than that of lung cancer patients. CONCLUSION: These results suggest that detection of intelectin-1 may be useful for a differential diagnosis of epithelioid-type MPM in immunohistochemistry and that a high concentration of intelectin-1 in pleural effusion can be used as a new marker for clinical diagnosis of MPM.

Self-production of tissue factor-coagulation factor VII complex by ovarian cancer cells.

BACKGROUND: Thromboembolic events are a major complication in ovarian cancer patients. Tissue factor (TF) is frequently overexpressed in ovarian cancer tissue and correlates with intravascular thrombosis. TF binds to coagulation factor VII (fVII), changing it to its active form, fVIIa. This leads to activation of the extrinsic coagulation cascade. fVII is produced by the liver and believed to be supplied from blood plasma at the site of coagulation. However, we recently showed that ovarian cancer cells express fVII transcripts under normoxia and that this transcription is inducible under hypoxia. These findings led us to hypothesise that ovarian cancer cells are intrinsically associated with TF-fVIIa coagulation activity, which could result in thrombosis. METHODS: In this study, we examined whether ectopically expressed fVII could cause thrombosis by means of immunohistochemistry, RT-PCR, western blotting and flow cytometry. RESULTS: Ectopic fVII expression occurs frequently in ovarian cancers, particularly in clear cell carcinoma. We further showed that ovarian cancer cells express TF-fVIIa on the cell surface under normoxia and that this procoagulant activity is enhanced by hypoxic stimuli. Moreover, we showed that ovarian cancer cells secrete microparticles (MPs) with TF-fVIIa activity. Production of this procoagulant secretion is enhanced under hypoxia. CONCLUSION: These results raise the possibility that cancer cell-derived TF-fVIIa could cause thrombotic events in ovarian cancer patients.

Incidence of Carboplatin-related hypersensitivity reactions in Japanese patients with gynecologic malignancies.

Carboplatin is one of the most commonly used and well-tolerated agents for gynecologic malignancies. The rate of hypersensitivity reactions (HSRs) in the overall population of patients receiving carboplatin has been reported to increase after multiple doses of the agent. We retrospectively analyzed the incidence, clinical features, management, or outcome of carboplatin-related HSRs in 113 Japanese patients with gynecologic malignancies and the possibility of rechallenge with the drug. We intravenously administered carboplatin after paclitaxel or docetaxel. Mild HSRs are resolved by temporary interruption of carboplatin infusion, an additional antihistamine, and/or a corticosteroid. If HSRs arose, carboplatin was diluted, not exceeding 1 mg/mL, and slowly infused over 2 hours in subsequent cycles. Ten patients experienced carboplatin HSRs, with an overall incidence of 8.85%. The first HSR episode was mild in all cases. When retreated with carboplatin, 4 exhibited severe HSRs. More than 9 cycles and/or more than 5000 mg of carboplatin administration significantly increased the incidence of HSRs. In particular, carboplatin treatment beyond 15 cycles and/or 8000 mg increased the risk of severe HSRs (P < 0.0001). The incidence of HSRs in the ovarian carcinoma group was significantly greater than that in the uterine carcinoma group (P = 0.0046). Careful attention should be paid to HSRs during carboplatin treatment beyond 9 cycles and/or 5000 mg. The rate of severe HSRs greatly increases beyond 15 cycles and/or 8000 mg. Further studies are needed to identify potential risk factors that may contribute to the development of carboplatin HSRs and to decrease the risk of reactions.

Can ABCF2 protein expression predict the prognosis of uterine cancer?

Uterine cervical and endometrial cancers are common malignant solid neoplasms for which there are no useful prognostic markers. In this study, we evaluate the relationship between ATP-binding cassette superfamily F2 (ABCF2) expression and clinical factors including clinical stage, histologic type, grade and prognosis in uterine cervical and endometrial cancer. Two hundred and sixty seven cervical and 103 endometrial cancers were studied. ATP-binding cassette superfamily F2 cytoplasmic expression was detected by immunohistochemical staining and scored as positive or negative. Among cervical cancer cases, 149 (55.8%) expressed ABCF2. The overall survival was longer in ABCF2-negative than ABCF2-positive cases (P=0.0069). Statistically significant prognostic factors for survival were ABCF2 positivity (risk ratio (rr)=1.437), old age (rr=1.550) and advanced stage (rr=2.577). ATP-binding cassette superfamily F2 positivity was an independent prognostic factor by multivariate proportional hazard test (P=0.0002). Among endometrial cancer cases, 72 (69.9%) were cytoplasmic ABCF2 positive. However, there was no significant relationship between ABCF2 expression and age, clinical stage, histologic type, histologic grade, oestrogen receptor status or prognosis. ATP-binding cassette superfamily F2 expression may be a useful prognostic marker in cervical but not endometrial cancer. The role of ABCF2 protein may differ depending on the type of cancer.

The feasibility of sentinel node biopsy in the previously treated breast.

PURPOSE: Sentinel lymph node biopsy (SNB) has been a standard technique in early breast cancer. However, it is not clear that the SNB procedure can be applied to second breast cancer or recurrence occurring in the previously treated breast. The purpose of this study was to clarify the feasibility of the SNB procedure in breast cancer occurring in the previously treated breast, and to investigate the factors related to altered lymphatic flow. PATIENTS AND METHODS: Between April 2004 and December 2006, 1490 patients underwent the breast SNB procedure. Among them, 31 patients had a history of previous treatments in the same breast. Recent excision biopsy cases were not included in this group. All patients had previous breast-conserving surgery in the same breast. Sixteen patients had axillary dissection, 3 had SNB, and 12 had no axillary treatment. Ten patients had received radiation therapy to the breast and axilla. Visualization of axillary nodes, internal mammary nodes and contralateral axillary nodes was evaluated and compared with pathological results. RESULTS: Axillary nodes were visualized in 23 patients, internal mammary nodes in 7 patients, and contralateral axillary nodes in 7 patients. The patients with previous axillary dissection exhibited altered lymph node distribution, but did not show involvement of contralateral axillary nodes. Visualization of contralateral axillary nodes occurred in 7 of the 10 patients with previous irradiation to breast irrespective of axillary dissection. Twenty-eight patients underwent SNB, 4 of whom showed cancer-positive nodes. Three patients were cancer-positive in non-ipsilateral axillary nodes (one patient showed positive opposite axillary node and two patients showed positive internal mammary nodes). CONCLUSION: Previous axillary dissection or irradiation to the breast greatly influences lymphatic flow. Irradiation to the breast may be a strong factor for the visualization of contralateral axillary nodes. Despite the frequent alteration of lymphatic flow, SNB seems to be feasible in secondary or recurrent breast cancer patients.

Display of the epileptogenic zone on the frontal cortical surface using dynamic voltage topography of ictal electrocorticographic discharges.

To evaluate the usefulness of computerized brain-surface dynamic voltage topography (DVT) of ictal electrocorticographic (ECoG) discharges to localize and identify epileptogenic areas, 3 patients with intractable frontal lobe epilepsy who underwent epilepsy surgery after chronic subdural electrode recording were assessed. Cortical surfaces and subdural electrodes were photographed during initial surgery to create an electrode map that could be superimposed onto a picture of the brain surface. DVT was performed by calculating sequential amplitudes of ictal ECoG discharges, which were then superimposed onto the cortical and electrode maps. In all cases, DVT clearly identified the ictal onset zone and the early propagation area on the operative field. DVT allowed recognition of spatial relationships between the epileptogenic area and structural abnormalities, functional cortex, and cortical veins; and was useful to decide on the resection area.

Novel heteroduplex method using small cytology specimens with a remarkably high success rate for analysing EGFR gene mutations with a significant correlation to gefitinib efficacy in non-small-cell lung cancer.

We conducted a feasibility study to examine whether small numbers of cancer cells could be utilised for analysis of the EGFR gene status using the loop-hybrid mobility shift assay, which is a modified heteroduplex technique. Cytology specimens obtained by transbronchial abrasion were successfully used for analysis of the EGFR gene status in 50 of 52 (96.2%) patients diagnosed with class V non-small-cell carcinoma. Furthermore, the relationship between the EGFR gene status and clinical outcome was analysed in 25 patients treated with gefitinib. Overall, 10 of 11 patients with EGFR mutations in exon 19 or 21 showed tumour regression with gefitinib treatment, compared to only two of 14 patients with wild-type EGFR. The response rate was significantly higher in the EGFR mutation group than in the wild-type EGFR group (90.9 vs 14.3%, P=0.00014). Logistic regression analysis revealed that EGFR mutations in cytology specimens represented an independent predictor of the gefitinib response. The overall and progression-free survivals were significantly longer in the EGFR mutation group than in the wild-type EGFR group (P<0.05). In conclusion, cytology specimens could be useful for analysing the EGFR status in the majority of patients with non-small-cell lung cancer to determine whether they are likely to benefit from gefitinib treatment.

Radioactivity thresholds for sentinel node biopsy in breast cancer.

AIMS: The aim of the present study is to clarify the level of radioactive lymph node should be biopsied after the most radioactive SN is removed. METHODS: SNB using radionuclide was performed in our hospital for 1179 primary breast cancers between April 2000 and October 2005; most (1177/1179) were performed successfully. Our criterion for harvesting SNs is to remove tissue until no radioactive site is present. The level of radioactivity and the order of removal of each lymph node were compared with pathologic results. RESULTS: More than 2 (overall average 1.9) radioactive SNs were biopsied in 686 of 1177 breasts. Cancer positive results were recorded for 142 breasts with multiple SNs. In 142 breasts, 64 showed metastasis to the most radioactive node only, 39 showed metastasis other than the most radioactive node only, and 39 showed the most radioactive node and other radioactive nodes. Moreover, if several other criteria were applied, false-positive cases were increased significantly. CONCLUSIONS: It is necessary to harvest radioactive lymph nodes other than the most radioactive. Moreover, efforts to remove every radioactive lymph node will minimize false-negative results.

The effect of an old surgical scar on sentinel node mapping in patients with breast cancer: a report of five cases.

AIMS: To study the significance of lymphatic drainage disruption due to a surgical scar in sentinel node mapping (SNM) in breast cancer patients. METHODS: We reviewed patients with stage I breast cancer who had undergone SNM and had an old surgical scar in the ipsilateral breast. RESULTS: Of 534 breast cancer patients who had undergone SNM, five patients had an old scar in the ipsilateral breast. Inter-pectoral nodes, internal nodes, intramammary nodes, and contralateral axillary nodes were identified as sentinel nodes in three cases. In the remaining two cases, no sentinel lymph nodes were identified. CONCLUSIONS: An old surgical scar in the breast may cause lymphatic drainage disruption, resulting in abnormal radioactive colloid uptake during SNM.

The pathologic impact of tacrolimus on protocol biopsy in renal transplant patients with basiliximab-based immunosuppression.

Forty-two ESRD patients underwent renal transplantation using basiliximab (mean age: 30.6 +/- 18.6 years at transplantation; male: 50%; ESRD duration: 51.6 +/- 13.0 months) between February, 2000 and July, 2003. All patients had a protocol biopsy on the day of transplant, on discharge from the hospital (35.5 +/- 13.2 days), and at 1 year after transplant. The immunosuppression included a calcineurin inhibitor, basiliximab, mycophenolate mofetil (MMF), and methylprednisolone. While 16 patients used tacrolimus (FK group: 29.4 +/- 16.6 years old), 26 patients used cyclosporine (CsA group: 31.4 +/- 20.1 years old). Protocol biopsies were graded according to the Banff 97 classification. The incidence of acute rejection episodes within 1 year was greater in the CsA (15%) than the FK group (6%). Serum creatinine at hospital discharge was similar (CsA: 1.01 +/- 0.59 mg/dL, FK: 0.97 +/- 0.49, p = .18); however creatinine at 1 year differed significantly (CyA: 1.22 +/- 0.88 mg/dL, FK: 0.92 +/- 0.39, P = .03). There was a trend toward an increase in the score of interstitial inflammations in the CsA group, while it remained constant in the FK cohort (P = .05 at 1 year between the two groups). Other pathologic scores (t, ci, ct, cv, ah) did not differ between the groups at 1 year. Although there were no differences in the demographics between the two groups, there were several trends toward better renal function in the FK group.

Spatio-temporal analysis by voltage topography of ictal electroencephalogram on MR surface anatomy scan for the localization of epileptogenic areas.

A 15-year-old girl developed intractable epilepsy following a right transcallosal resection of the intraventricular teratoma. Magnetic resonance (MR) imaging showed a T (2)-prolonged subcortical lesion in the right frontal lobe as well as a residual intraventricular tumor. The integration of the voltage topography of ictal onset activities of the scalp-recorded electroencephalogram (EEG) and a surface anatomy scan of MR images clearly revealed the epileptogenic area on the cortex above the subcortical lesion, with the propagation pattern towards the frontopolar area. Excision of the epileptogenic cortex and underlying gliosis resulted in a successful cessation of the epilepsy. This non-invasive EEG technique provided useful information that accurately localized the epileptogenic area on a large structural abnormality without invasive intracranial electrocorticographic monitoring.

Association of MBL gene polymorphisms with major bacterial infection in patients treated with high-dose chemotherapy and autologous PBSCT.

A growing body of evidence indicates that genetic factors are involved in an increased risk of infection. We investigated whether mannose-binding lectin (MBL) gene polymorphisms that cause low levels of MBL are associated with the occurrence of major infections in patients, mainly bearing hematological malignancies, after high-dose chemotherapy (HDT) rescued by autologous peripheral blood stem cell transplantation (auto-PBSCT). A retrospective evaluation of 113 patients treated with HDT and auto-PBSCT revealed that the low-producing genotypes, B/B and B/LXA, were associated with major bacterial infection (P=0.0016, OR 7.9). We next performed a nation-wide large-scale study to assess the allele frequency of the MBL coding mutation in a total of 2623 healthy individuals in Japan. The frequency of allele B was estimated to be approximately 0.2, almost the same in seven different areas of Japan. This common occurrence suggests that MBL deficiency may play an important role in the clinical settings of immunosuppression.

Raised serum APRIL levels in patients with systemic lupus erythematosus.

OBJECTIVE: To determine whether serum levels of a proliferation-inducing ligand (APRIL) are raised in patients with systemic lupus erythematosus (SLE) and correlate with autoantibody titres or disease activity, or both. METHODS: Serum samples from 48 patients with SLE, 41 normal healthy subjects, and 21 patients with rheumatoid arthritis (RA) were assayed for APRIL by enzyme linked immunosorbent assay. Medical charts were retrospectively reviewed for autoantibody titres and immunoglobulin levels. Disease activity was assessed using the British Isles Lupus Assessment Group (BILAG) index. RESULTS: The APRIL levels in the serum samples from patients with SLE were significantly higher than in those from healthy controls and those from patients with RA. Serum APRIL levels did not correlate with serum IgG and IgM levels, but had a tendency to correlate with anti-double stranded DNA antibody titres. Moreover, serum APRIL levels correlated significantly with musculoskeletal manifestations among patients with SLE when assessed by the BILAG index. CONCLUSION: APRIL may be an important factor in raised autoantibody titres and musculoskeletal disease in patients with SLE. Patients with raised serum APRIL levels may be ideal candidates for therapeutic targeting of APRIL.

Vim thalamotomy for Holmes' tremor secondary to midbrain tumour.

Holmes' (rubral or midbrain) tremor is an unusual combination of 2 Hz to 5 Hz rest, postural, and kinetic tremors of an upper extremity. This tremor has been considered to result from the lesions in the vicinity of the red nucleus in the midbrain. There has been no systematic analysis of the surgical target in the Holmes' tremor so far of nucleus ventrointermedius (Vim) or globus pallidus interna. This 26 year old man gradually developed a disabling midbrain tremor involving both the distal and proximal parts of the left upper arm. Additional neurological findings included oculomotor palsy and ataxia of the left arm. On the radiological studies, a mass lesion (germinoma) was found on the midbrain tegmentum, which was treated by conventional radiation therapy. Although there was improvement in the radiological imaging, his midbrain tremor became intolerable despite medical treatment. The authors performed MR guided stereotactic Vim thalamotomy. With radiofrequency lesioning in the right Vim, his resting, postural, and action tremors were much alleviated in both the distal and proximal parts of the left upper extremity. The authors consider that Vim thalamotomy is still an effective means of controlling midbrain tremors involving the proximal upper limb.