In the present study, we evaluated the safety and effectiveness of SYT-SSX-derived peptide vaccines in patients with advanced synovial sarcoma. A 9-mer peptide spanning the SYT-SSX fusion region (B peptide) and its HLA-A*2402 anchor substitute (K9I) were synthesized. In Protocols A1 and A2, vaccines with peptide alone were administered subcutaneously six times at 14-day intervals. The B peptide was used in Protocol A1, whereas the K9I peptide was used in Protocol A2. In Protocols B1 and B2, the peptide was mixed with incomplete Freund's adjuvant and then administered subcutaneously six times at 14-day intervals. In addition, interferon-a was injected subcutaneously on the same day and again 3 days after the vaccination. The B peptide and K9I peptide were used in Protocols B1 and B2, respectively. In total, 21 patients (12 men, nine women; mean age 43.6 years) were enrolled in the present study. Each patient had multiple metastatic lesions of the lung. Thirteen patients completed the six-injection vaccination schedule. One patient developed intracerebral hemorrhage after the second vaccination. Delayed-type hypersensitivity skin tests were negative in all patients. Nine patients showed a greater than twofold increase in the frequency of CTLs in tetramer analysis. Recognized disease progression occurred in all but one of the nine patients in Protocols A1 and A2. In contrast, half the 12 patients had stable disease during the vaccination period in Protocols B1 and B2. Of note, one patient showed transient shrinkage of a metastatic lesion. The response of the patients to the B protocols is encouraging and warrants further investigation. (Cancer Sci 2012; 103: 1625-1630 S ynovial sarcoma is a malignant tumor of soft tissue characterized by biphasic or monophasic histology, specific chromosomal translocation t(X;18), and its resultant SYT-SSX fusion genes.(1,2) Reported 5-year survival rates of patients with synovial sarcoma range from 64% to 77%.(3-7) In contrast, most metastatic or relapsed diseases remain incurable, indicating a need for new therapeutic options other than conventional surgery, radiotherapy, and chemotherapy.Antigen-specific peptide immunotherapy is one such option. (8)(9)(10)(11)(12) Previously, we demonstrated that SYT-SSX fusion gene-derived peptides (wild type and agretope modified) are recognized by circulating CD8 + T cells in HLA-A24 + patients with synovial sarcoma and elicit human leukocyte antigen (HLA)-restricted, tumor-specific cytotoxic responses. (13,14) Subsequent to these preclinical studies, we started a pilot clinical trial with a wild-type SYT-SSX-derived peptide vaccine. (15) In the present study, we evaluated immunologic and clinical outcomes of the vaccination trials using an agretope-modified SYT-SSX peptide and a combination of the peptide vaccine with adjuvant and interferon (IFN)-a.
Ureterolithiasis is one of the most frequently diagnosed urologic diseases worldwide. Its annual incidence in Japan increased three-fold from 1965 to 2005. Ureterolithiasis incidence is affected by numerous factors, including race, sex, body weight, fluid intake, and climate. Here, we aimed to address the latter by considering the effect of seasonal variation on stone incidence and incorporating this information into a predictive model for differential diagnosis of ureteral stone from other conditions with similar presentations. We retrospectively identified 491 patients in our emergency department computer database who complained of back, flank, or lower abdominal pain during 2007–2015. Among them, 358 had stones, as confirmed by computerized tomography or plain abdominal X-ray of kidney–ureter–bladder. We also charted the mean ambient temperatures in our city for a year. The cases of ureteral stones paralleled the ambient temperatures, peaking during the hottest weather. Univariate analysis identified 13 factors associated with ureteral stones. Multivariate analysis narrowed the number to eight: age <60 years, male sex, short duration of pain (<6 h), nausea/vomiting, hydronephrosis, hematuria, history of urinary stone(s), and summer (July–September in Japan). Pain appearing during summer was nine times more likely to be due to a ureteral stone than was pain appearing during other seasons. We incorporated the eight variables identified into a predictive logistic regression model, which yielded good prediction of ureteral stones. Awareness that hot weather is associated with increased incidence of ureterolithiasis could facilitate differential diagnosis, and our prediction model could be useful for screening for ureterolithiasis.
The simplified CHOKAI score is a useful tool to screen for ureteral stones in patients with renal colic.
Malignant glomus tumor is an extremely rare neoplasm and its histological features are not well characterized. We report a 16-year-old female patient with a malignant glomus tumor. The patient was admitted to our hospital presenting with a mass in the right upper arm that she had noticed for the previous 6 months. Computed tomography and magnetic resonance imaging revealed an expanded mass involving the surrounding tissues. At surgery, an ill-defined and expanded mass was found, 5 x 4 x 3 cm in size, in the right branchial muscle. The tumor was extirpated, along with neighboring muscle tissues. Histologically, tumor cells were round to short-spindle shaped, forming solid sheets admixed with vessels of varying size. Their nuclei were uniformly oval to round, and their cytoplasms were slightly eosinophilic. The growth pattern of the tumor cells resembled that of glomus tumor, but mitotic figures were frequent (as high as 10 per 10 high-power fields). Immunohistochemically, the tumor cells were positive for vimentin and muscle actin, but negative for desmin. There were no areas typical of benign glomus tumor or sarcomatous change. These findings led us to a diagnosis of primary malignant glomus tumor arising de novo. There has been no recurrence or metastasis for 21 months after wide excision.
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