Induction of tumor-specific CD8+ cytotoxic T lymphocytes from naïve human T cells by using Mycobacterium-derived mycolic acid and lipoarabinomannan-stimulated dendritic cells.

The main effectors in tumor control are the class I MHC molecule-restricted CD8+ cytotoxic T lymphocytes (CTLs). Tumor-specific CTL induction can be regulated by dendritic cells (DCs) expressing both tumor-derived epitopes and co-stimulatory molecules. Immunosuppressive tolerogenic DCs, having down-regulated co-stimulatory molecules, are seen within the tumor mass and can suppress tumor-specific CTL induction. The tolerogenic DCs expressing down-regulated XCR1+CD141+ appear to be induced by tumor-derived soluble factors or dexamethasone, while the immunogenic DCs usually express XCR1+CD141+ molecules with a cross-presentation function in humans. Thus, if tolerogenic DCs can be reactivated into immunogenic DCs with sufficient co-stimulatory molecules, tumor-specific CD8+ CTLs can be primed and activated in vivo. In the present study, we converted human tolerogenic CD141+ DCs with enhanced co-stimulatory molecule expression of CD40, CD80, and CD86 through stimulation with non-toxic mycobacterial lipids such as mycolic acid (MA) and lipoarabinomannan (LAM), which synergistically enhanced both co-stimulatory molecule expression and interleukin (IL)-12 secretion by XCR1+CD141+ DCs. Moreover, MA and LAM-stimulated DCs captured tumor antigens and presented tumor epitope(s) in association with class I MHCs and sufficient upregulated co-stimulatory molecules to prime naïve CD3+ T cells to become CD8+ tumor-specific CTLs. Repeat CD141+ DC stimulation with MA and LAM augmented the secretion of IL-12. These findings provide us a new method for altering the tumor environment by converting tolerogenic DCs to immunogenic DCs with MA and LAM from Mycobacterium tuberculosis.

Safety of Abiraterone Acetate Administration in Elderly Patients Receiving Peritoneal Dialysis with Castration-Resistant Prostate Cancer: Two Case Reports.

We report two elderly patients receiving peritoneal dialysis with castration-resistant prostate cancer (CRPC). Herein, we show that the patients were safely treated using abiraterone acetate (750 mg/day orally once daily) and prednisolone (5 mg/day orally once daily). Although the prostate-specific antigen (PSA) level increased in both cases, there was no manifestation of disease progression (clinical and radiographic) for 22 months in case 1 and 8 months in case 2. In case 2, the only adverse event was hypokalemia, which was treated using potassium preparations.

Efficacy of a thermoexpandable metallic prostate stent (Memokath) in elderly patients with urethral obstruction requiring long-term management with urethral Foley catheters.

AIM: To investigate whether the insertion of a thermoexpandable metallic prostate stent (Memokath) facilitates the removal of Foley catheters in elderly patients ineligible for urethral obstruction surgery because of the potential complications involved in long-term catheter management. METHODS: A total of 37 male patients (mean age 79.8 ± 6.2 years) ineligible for surgery under general anesthesia because of advanced age, the presence of post-cerebrovascular disorders or anticoagulant therapy use and who subsequently had a Memokath stent inserted between June 2007 and November 2009 were enrolled in the present study. Patients with spinal injury were excluded. We compared the correlation between prostatic urethral length and total prostate volume (TPV). We also evaluated the postoperative postvoid residual (PVR) and presence of pyuria, and reviewed postoperative complications and unassisted urination ability. RESULTS: We found a positive correlation between prostatic urethral length and TPV. After the insertion of the Memokath stent, the catheters were removed from all patients who could urinate unassisted. The PVR was <50 mL in 76.4% patients, and there was a 52% improvement in pyuria after insertion of the Memokath stent. The mean postoperative follow-up duration was 33.2 ± 16.7 months. A total of 21 patients (56.7%) were able to urinate unassisted after receiving the Memokath stent. Unassisted urination was difficult in patients with poor performance status. No serious complications were observed after insertion of the Memokath stent. CONCLUSIONS: The Memokath stent was safe and useful for elderly patients with urethral obstruction and good performance status requiring long-term management with urethral Foley catheters.

Efficacy of transurethral resection of the bladder tumor (TUR-BT) for huge bladder cancer.

There are no guidelines regarding whether to perform either a radical transurethral resection of the bladder tumor (TUR-BT) or a total cystectomy after TUR biopsy for huge bladder cancer, and this decision is entrusted to each institution. Of 439 patients in whom TUR-BT was performed from 2005 through 2009, the weight of the total resected volume was > 50 g in 6 patients, and among these 6 patients the following variables were compared: operating time, weight of resected volume, transfusion volume, presence or absence of hydronephrosis, preoperative urinary cytology, serum cytokeratin 19 fragment (CYFRA) level, intraoperative bladder compliance, and histopathological findings. The median age, operating time, weight of resected volume, transfusion volume, and length of follow-up were 72 years, 300 minutes, 88 g, 202 mL, 16 months, respectively. The serum CYFRA level in patients with muscle-invasive cancer (11.8 ng/mL) was higher than that in patients with non-muscle-invasive cancer (5.06 ng/mL). All patients with non-muscle-invasive bladder cancer survived without recurrence. Although the mean length of follow-up was only 16 months (5-59 months), the 1 patient who was followed up for 59 months had no recurrence. In cases of muscle-invasive bladder cancer, all patients, except for a relatively recent patient, have died. In cases without muscle invasion, lymph node metastasis, distal metastasis, or preoperative renal dysfunction accompanied by hydronephrosis, with favorable bladder compliance, we believe that radical TUR-BT should be actively performed to preserve the bladder. A second TUR-BT should be performed in cases of non-muscle-invasive cancer without G3 components to treat the huge bladder cancer.

Neuroendocrine differentiation of localized prostate cancer during endocrine therapy.

A 74-year-old male was treated with endocrine therapy for localized prostate cancer. After 25 months he complained of a swollen neck, and was diagnosed with prostate cancer with lymph node metastasis of neuroendocrine differentiation. Neuroendocrine differentiation without elevation of conventional tumor markers is rare during the initial recurrent course of localized prostate cancer.

[The clinical status of prostate cancer in elderly patients 75 years of age or older in the Kitamurayama District of Yamagata Prefecture, Japan].

To evaluate the present status of prostate cancer in patients 75 years of age or older, we reviewed clinical characteristics of prostate cancer in patients from the Kitamurayama Hospital. The number of symptomatic advanced cases was greater in patients > or = 75 years old compared with patients < or = 74 years old. However, no significant difference in cause-specific survival rate was found between the two groups. In the cases examined, the difference in biological characteristics between groups did not affect the prognosis. On the other hand, for patients > or = 75 years old, improvement of urinary retention was low, and the incidence of adverse drug responses to endocrine therapy, such as dementia and thrombosis, was high. We recognize the necessity of a comprehensive medical plan that attaches importance to quality of life and safety for the treatment of patients over 75 years old with prostate cancer.

[A case of granulomatous orchitis].

A 66-year-old man came to us with a chief complaint of painful right scrotal swelling. The right testis was enlarged on the ultrasound gray scale, but the inside was homogeneous. A power Doppler ultrasound showed slightly increased vascular flow in the periphery of the right testis. As the soluble IL-2 receptor was 527 U/ml (normal: 220-530 U/ml), we considered malignant lymphoma and performed high orchiectomy. On pathological examination, the tumor was diagnosed as granulomatous orchitis. To our knowledge, this is the 21st case in Japan.

A case of non-small cell lung cancer with false-positive staging by positron emission tomography.

A 70-year-old woman with right lung cancer was admitted to our hospital. Chest computed tomography (CT) revealed an approximate 2.5 cm sized mass in the right middle lobe, and enlarged hilar and mediastinal lymph nodes. The 2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) showed high uptake in the right hilar and mediastinal nodes. Therefore we diagnosed N2 (mediastinal nodal involvement) disease. Microscopically, however, all dissected lymph nodes revealed anthracosilicosis and negative for malignancy. Although false-positive evaluation of mediastinal involvement by PET can occur in the setting of metabolically active inflammatory disease, this case did not have these active diseases. The FDG-PET result of this case was unusual.