Ischemic Stroke Caused by Carotid Stump at the Common Carotid Artery.

An 84-year-old man developed motor aphasia and right hemiparesis on postoperative day 1 after orchiectomy for suspected malignant lymphoma. He had a history of thoracic endovascular aortic repair for aortic aneurysm using a bypass graft from the right subclavian artery to the left common carotid artery (CCA); however, the graft had become occluded six months later. Brain magnetic resonance imaging revealed acute cerebral infarctions in the left frontal lobe. Carotid ultrasonography revealed a stump at the left CCA, just below the bifurcation, formed by the occluded graft with an oscillating thrombus. This case was rare in that a CCA stump was identified as the embolic source of ischemic stroke.

Predictive factors of biochemical recurrence after radical prostatectomy for high-risk prostate cancer.

OBJECTIVE: To identify risk factors of biochemical recurrence after radical prostatectomy in high-risk patients. METHODS: A total of 191 high-risk prostate cancer patients according to the D'Amico classification treated with radical prostatectomy at a single institution between April 2000 and December 2013 were enrolled. The pathological evaluation including intraductal carcinoma of prostate was reassessed, and the clinical and pathological risk factors of biochemical recurrence were analyzed. RESULTS: The median follow up after radical prostatectomy was 49 months. The 5-year biochemical recurrence-free survival rate after radical prostatectomy in high-risk prostate cancer patients was 41.6%. Initial prostate-specific antigen, pathological Gleason score, seminal vesicle invasion, extraprostatic extension and intraductal carcinoma of the prostate were significantly associated with biochemical recurrence-free survival. The 5-year biochemical recurrence-free survival rates in patients with zero, one, two and three of these risk factors were 92.9%, 70.7%, 38.3% and 28.8%, respectively. In patients with four or more factors, the biochemical recurrence-free survival rate was 6.1% after 18 months. CONCLUSIONS: In D'Amico high-risk patients treated with radical prostatectomy, risk factors for biochemical recurrence can be identified. Patients with fewer risk factors have longer biochemical recurrence-free survival, even among these high-risk cases.

[SIGNIFICANCE OF INTRADUCTAL CARCINOMA OF THE PROSTATE IN POST-OPERATIVE BIOCHEMICAL RECURRENCE].

(Objective) We investigated the prognostic significance of intraductal carcinoma of the prostate (IDC-P) in radical prostatectomy specimens. (Materials and methods) We evaluated 441 patients treated with radical prostatectomy and analyzed data on IDC-P, lymph node metastases, Gleason score, seminal vesicle invasion, extraprostatic extension, surgical margin, total cancer volume, and zonal origin of dominant cancer focus in radical prostatectomy specimens. The median follow-up was 50 months (range 6-164 months). (Results) We identified IDC-P in 112 cases (25.4%). The five-year biochemical progression-free survival rate in patients with IDC-P was significantly lower than for those without IDC-P (35.8% vs 69.6%; p<0.0001). In a univariate analysis, IDC-P (p<0.0001), lymph node metastases (p=0.0022), Gleason score (p<0.0001), seminal vesicle invasion (p<0.0001), extraprostatic extension (p<0.0001), surgical margin (p<0.0001) and total cancer volume (p<0.0001) were significantly associated with the biochemical progression-free survival. In a multivariate analysis, Gleason score (p<0.0001), IDC-P (p=0.0002), seminal vesicle invasion (p=0.0011), extraprostatic extension (p=0.0012), surgical margin (p=0.0019) and lymph node metastases (p=0.0402) were significantly associated with biochemical progression-free survival. (Conclusions) The presence of IDC-P is an independent factor of biochemical recurrence in prostate cancer patients treated with radical prostatectomy. We therefore recommend that the presence of IDC-P in radical prostatectomy specimens be reported.

[Significance of the antimicrobial drug used to prevent febrile infection following prostate needle biopsy].

The rate of incidence of febrile infection and the antimicrobial drug used at the time of prostate needle biopsy was examined retrospectively. SPFX (sparfloxacin) 400 mg (January 2007 to March 2010) and LVFX (levofloxacin) 500 mg (April 2010, onward) were administered prophylactically in 1,034 patients undergoing transrectal or transperineal prostate biopsy. One febrile infection occurred and resolved in each group. A single dose of LVFX 500 mg before the procedure effectively prevented febrile infection in both transrectal and transperineal prostate needle biopsy.

[Distribution of intraductal carcinoma of the prostate and associated lesions in the cancer foci on radical prostatectomy specimens].

OBJECTIVE: The distribution of intraductal carcinoma of the prostate (IDC-P) and other intraductal lesions associated with IDC-P was evaluated in the cancer foci on radical prostatectomy specimens. MATERIALS AND METHODS: We reviewed slide in 412 cases treated by radical prostatectomy without neoadjuvant therapy. Mapping study was performed with regard to IDC-P, other intraductal lesions associated with IDC-P and invasive carcinoma. RESULTS: We identified 98 cases (23.8%) and 102 cancer foci associated with IDC-P. In these all cancer foci, IDC-P was associated with invasive carcinoma and other intraductal neoplastic lesions with tufting, micropapillary and loose cribriform patterns were contiguous and admixed with IDC-P in 83 cancer foci (81.4%). There were lesions with invasive carcinoma around the IDC-P in 95 cancer foci (93.1%) and lesions without invasive carcinoma around IDC-P in 66 foci (64.7%). The latter lesions existed in the marginal areas of the cancer foci in 63 (61.8%) and in the central areas of the cancer foci in 14 (13.7%). In 5 cancer foci (4.9%), volume of IDC-P was larger than that of invasive carcinoma. CONCLUSIONS: The distribution of IDC-P with dense cribriform and solid patterns varied in cancer foci, and intraductal lesions with tufting, micropapillary and loose cribriform patterns were frequently seen in area contiguous and admixed with IDC-P. The latter lesion may be low grade morphology of IDC-P, although the lesions could not be distinguished from high grade prostatic intraepithelial neoplasia.

Donor CD4 T cells are critical in allogeneic stem cell transplantation against murine solid tumor.

Nonmyeloablative allogeneic stem cell transplantation (SCT) has been used for various malignancies, although detailed mechanisms of antitumor effects remain unclear. We showed that a nonmyeloablative allogeneic SCT regimen, which consists of mixed chimerism induced by an injection of donor spleen and bone marrow cells followed by cyclophosphamide treatment and a donor lymphocyte infusion (DLI), exerted antitumor effects on established murine bladder tumor, MBT-2. An expansion of donor CD4 T cells accompanied by transient but vigorous IFN-gamma production was detected shortly after DLI. In vivo neutralization of IFN-gamma or depletion of CD4 T cells from DLI abolished the antitumor effects, indicating an indispensable role of donor CD4 T cells producing IFN-gamma. Donor as well as host CD8 T cells accumulated in the tumor region with time. Importantly, depletion of CD8 T cells from DLI did not reverse the suppression of tumor growth, indicating that CD4 T cells play a more essential role in mediating early antitumor effects. Furthermore, tumor-specific response of host CD8 T cells was suggested. These results not only provide the first evidence of nonmyeloablative allogeneic SCT for the treatment of bladder tumor but also elucidate detailed mechanisms of antitumor effects provoked by DLI.

What affects the results of a laparoscopic adrenalectomy for pheochromocytoma? Evaluation with respect to intraoperative blood pressure and state of tumor.

PURPOSE: To investigate the factors that affect the operative data and to evaluate the validity of a laparoscopic adrenalectomy (LA) for pheochromocytoma. PATIENTS AND METHODS: Between July 1993 and January 2008, 172 LAs were performed in this department, and 34 of them were for pheochromocytoma. The characteristics and operative data of LAs for pheochromocytoma were examined with respect to the intraoperative systolic blood pressure (SBP) and the side of tumor. RESULTS: The intraoperative SBP rose to 180 mm Hg or more in 17 (50%) cases of LAs for pheochromocytomas. The analysis of SBP (<180 versus >180 mm Hg), however, showed that there were no differences in the operative data between the two groups. The tumor size was significantly associated with operative time (P < 0.05) or the blood loss (P < 0.05) in an LA for pheochromocytoma. The blood loss in LAs for right adrenal tumors was greater (150 versus 79 mL) than for left tumors (P < 0.01). In particular, some procedures for right large tumors had considerable blood loss and long procedural time. In a comparison of the operative data between pheochromocytoma and other adrenal tumors, the tumor was larger (4.3 versus 2.5 cm) and the blood loss was greater (100 versus 30 mL) than for other adrenal tumors. CONCLUSIONS: The operative data showed no correlation with the intraoperative high SBP, but they were associated with the tumor state. Although the procedure seems to be influenced by the size and state of tumor, LA is not contraindicated for pheochromocytoma, and it can therefore be performed safely.

Allogeneic cell therapy from immunized donors with tumor antigen peptide enhances the antitumor effect after cyclophosphamide-using non-myeloablative allogeneic hematopoietic cell transplantation.

Non-myeloablative allogeneic stem cell transplantation is an option for the treatment of hematological malignancies as well as solid tumors. We recently proposed a cyclophosphamide-using non-myeloablative cell therapy in which donor lymphocytes infusion (DLI) was carried out after tolerance induction to donor cells. In this study, we tested the possibility that the cyclophosphamide-using cell therapy could be augmented by pre-immunization of donors before DLI. We initially assessed whether or not the cyclophosphamide-using cell therapy could also show antitumor effect against subcutaneously established colon 26 carcinoma. As a tumor antigen-derived peptide for colon 26, we used AH1, an immunodominant H-2Ld-binding peptide derived from the envelope protein (gp70) of an endogenous murine leukemia virus. The cyclophosphamide-using cell therapy with the DLI from donors which were pre-immunized with the AH1 peptide was compared with that from non-immunized mice. The cyclophosphamide-using cell therapy significantly suppressed subcutaneously established colon 26 carcinoma, and the tumor-rejected mice acquired the tumor-specific protective immunity. When combined with the DLI from donors that were immunized with AH1, antitumor effect of the cyclophosphamide-using cell therapy was significantly augmented. The DLI from tumor peptide-immunized donors showed no influence on donor chimerism and bodyweight of the treated mice, indicating no increased risk of graft-versus-host disease. Tumor-specific cytotoxic T lymphocytes could be generated from tumor-rejected mice. Our results indicate that the cyclophosphamide-using non-myeloablative cell therapy with the DLI from tumor peptide-immunized donors is a useful protocol to augment graft-versus-tumor effect without exacerbation of graft-versus-host disease.

Dendritic cell therapy in combination with interferon-alpha for the treatment of metastatic renal cell carcinoma.

OBJECTIVES: To evaluate the safety and efficacy of dendritic cell (DC) therapy in combination with interferon-alpha (IFN-alpha) in patients with advanced renal cell carcinoma. METHODS: Seven patients, with progressive disease following IFN-alpha and interleukin (IL)-2 treatment, were treated with monocyte-derived DC (Mo-DC) and IFN-alpha between February 2004 and September 2006. They received Mo-DC once a week for 5 weeks and then every 2 weeks either intradermally or intratumorally. IFN-alpha (5-6 million U) was subcutaneously administered three times a week. Tumor size was evaluated by computed tomography scans before and after the 5th and 10th DC vaccination. A delayed-type hypersensitivity test was performed after the 4th and 5th DC administration for immunological monitoring. RESULTS: Five patients had stable disease while the remaining two patients had progressive disease following 4 months of vaccination. In six patients the time to progression was prolonged in comparison with the previous cytokine treatment. Six patients showed delayed-type hypersensitivity after the 4th or 5th immunization. Three patients developed high fever following DC immunization. Treatment was associated with transient flu-like symptoms. CONCLUSIONS: Our data indicate that DC therapy combined with IFN-alpha is safe and has the potential for prolonging the time to progression in patients with advanced renal cell carcinoma.

Posttransplant administration of cyclophosphamide and donor lymphocyte infusion induces potent antitumor immunity to solid tumor.

PURPOSE: Nonmyeloablative allogeneic stem cell transplantation (SCT) has been increasingly used for the treatment of hematologic and solid malignancies, and mature donor T cells are considered to be the main effectors of the graft-versus-tumor (GVT) activity. However, the association between degree of donor chimerism and intensity of GVT effects has not been fully elucidated. We recently proposed a unique nonmyeloablative cell therapy using posttransplant cyclophosphamide and donor lymphocyte infusion, by which a significant antitumor effect against murine renal cell carcinoma, RENCA, was induced, although the level of mixed chimerism was relatively low. In this study, we attempted to clarify a role of chimerism for in vivo antitumor effects on GVT effects in radiation-associated nonmyeloablative SCT. EXPERIMENTAL DESIGN: We assessed antitumor effects on RENCA tumors and the degree of donor chimerism after several doses of irradiation followed by allogeneic SCT and compared the results with those of cyclophosphamide-based cell therapy. RESULTS: Allogeneic SCT following sublethal irradiation (6 Gy) induced almost complete donor chimerism, whereas cyclophosphamide-based cell therapy produced low levels of donor chimerism. Nonetheless, GVT activity was much more potent in cyclophosphamide-based cell therapy than irradiation-conditioned SCT. Furthermore, cyclophosphamide-conditioned SCT induced more potent immune reconstitution with less severe graft-versus-host disease than irradiation-conditioned SCT. CONCLUSIONS: Our results indicate that a high level of chimerism is not essential for the in vivo antitumor effect of nonmyeloablative allogeneic cell therapy against solid tumor and that the recovery of peripheral lymphocytes after the initial immunosuppression might be a critical event for the elicitation of in vivo antitumor effects of that treatment modality.

The efficacy of laparoscopic radical nephrectomy for renal cell cancer in the elderly: an oncological outcome analysis.

OBJECTIVES: The efficacy and outcome of a laparoscopic radical nephrectomy (LRN) were retrospectively evaluated in patients aged >or=70 years, and the results were compared with those obtained from patients younger than 70 years undergoing laparoscopic surgery for the same indications. METHODS: Data were collected for all patients undergoing an LRN for renal cell carcinoma between March 1999 and November 2006. A total of 129 LRN were performed. There were 34 elderly patients (>or=70 years) and 95 adult patients (<70 years). The two groups were compared for comorbidity, previous surgical history, operative time, estimated blood loss, tumor size, complications during and after surgery, time to oral intake/ambulation, hospital stay, overall survival and disease free survival rates. RESULTS: In preoperative comorbid conditions, the number of patients with hypertension/ischemic heart disease in the elderly group was significantly greater than that in the adult group (p = 0.01). The elderly group had a mean operative time (247 min vs. 244 min) and blood loss (120 ml vs. 180 ml) similar to those in the adult group. In addition, the incidence of perioperative complications was not different between the two groups (intra-op: 2.9% vs. 5.3%/ post-op: 8.8% vs. 4.2%). All other variables before, during and after surgery were compatible between the two groups. CONCLUSIONS: The efficacy and oncological outcome of laparoscopic surgery in elderly patients was as promising as those in their younger counterparts. Therefore, elderly patients should not be excluded from undergoing an LRN, even though they usually present with more comorbidities.

Laparoscopic adrenalectomy for malignant tumors.

OBJECTIVES: The treatment of malignant adrenal tumors using laparoscopic surgery remains controversial. We thus compared the perioperative outcome of the laparoscopic adrenalectomy for the treatment of malignant tumors with the outcome for benign tumors. We also evaluated the oncological outcome of the laparoscopic adrenalectomy for a malignancy. METHODS: Since 1999 a total of nine laparoscopic adrenalectomies for a malignancy have been performed in nine patients. The median adrenal tumor size was 3 cm. The laparoscopic approach was transperitoneal in all cases. Seven patients had no evidence of a systemic metastatic disease, whereas two patients with a metastatic renal cell carcinoma had systemic metastatic disease at the time of the operation. RESULTS: The median operation time was 165 min and the estimated blood loss was 75 mL in the laparoscopic adrenalectomy for a malignancy. There was no significant difference between laparoscopic adrenalectomy for malignant and benign tumors. Regarding the oncological outcome, seven of the nine patients, including the two palliative cases, treated with a laparoscopic adrenalectomy for a malignancy were alive at a median follow-up of 20 months. One patient died of other causes. CONCLUSIONS: Our results clearly indicate that a laparoscopic adrenalectomy for the treatment of a metastatic adrenal malignancy can be performed with an acceptable outcome as a minimally invasive method in carefully selected patients.

Cyclophosphamide-using nonmyeloablative allogeneic cell therapy against renal cancer with a reduced risk of graft-versus-host disease.

PURPOSE: Much attention has been paid to nonmyeloablative allogeneic stem cell transplantation for the treatment of renal cancer. We recently proposed a cyclophosphamide-using nonmyeloablative cell therapy in which donor lymphocyte infusion (DLI) was carried out after the tolerance induction to donor cells. In considering the clinical application of the cyclophosphamide-using cell therapy, attempts to reduce graft-versus-host disease (GVHD) are crucial. The aim of the present study was to modify the cyclophosphamide-using cell therapy to reduce the risk of GVHD while preserving the antitumor activity against renal cancer. EXPERIMENTAL DESIGN: We assessed whether a delay in performing DLI from day 1 to day 5 after the cyclophosphamide treatment could reduce the risk of GVHD while preserving antitumor activity against RENCA, a murine carcinogen-induced renal cell carcinoma, in the cyclophosphamide-using cell therapy. RESULTS: Regarding the in vivo antitumor effect, there was no difference between DLI on day 1 and day 5 after the cyclophosphamide treatment, whereas the histologic findings of the small intestine showed that the cyclophosphamide-using cell therapy with DLI on day 5 decreased the risk of GVHD. In addition, the acquired immunity against RENCA was also observed in the RENCA-rejected mice that had been treated with DLI on day 5. CONCLUSIONS: Our results show that a delay in DLI during cyclophosphamide-using nonmyeloablative cell therapy can dissociate graft-versus-tumor effects from GVHD by reducing the risk of GVHD.

Comparison of standard and hand-assisted laparoscopic radical nephrectomy for renal cell carcinoma.

A laparoscopic radical nephrectomy (LRN) for renal cancer can be performed using two methods, hand-assisted laparoscopic surgery (HALS) and standard laparoscopic surgery (SLS). This institute initially used HALS to perform all radical nephrectomy, but gradually shifted to SLS. This study compared the two methods of radical nephrectomy: HALS vs. SLS, which were performed at a single institute. From March 1999 to November 2006, a total 129 patients with pathologically confirmed renal cell carcinoma underwent LRN, including 73 patients with the HALS and 56 patients with SLS. The median operative time was 264 minutes, and median estimated blood loss was 200 ml in the HALS group, respectively. The median operative time and median estimated blood loss in the SLS were 215 minutes and 100 ml, respectively. There was no significant difference in either the operative time or estimated blood loss between HALS and SLS. The median time to both postoperative oral intake and ambulation in the SLS were 1 day. Neither of these events after SLS was significantly shorter than that after HALS. The 4-year disease-free and overall survival rates in the HALS patients were 97.5% and 98.2%, respectively. Both the 4-year disease-free and overall survival rates in the SLS patients were 100%. Since no significant differences were observed between the two operative methods (SLS and HALS) regarding the operative data, postoperative course and oncological outcome, the surgical method for LRN can be selected according to characteristics of each surgical method.