External Validation of a Prognostic Model Predicting Metastatic Castration-Resistant Prostate Cancer Survival in Patients Receiving Post-Docetaxel Second-Line Chemotherapy.

Introduction: The Halabi model predicts the overall survival (OS) of patients with metastatic castration-resistant prostate cancer (mCRPC) treated with second-line therapy after docetaxel. We aimed to validate this model externally with an independent cohort, outside the setting of a clinical trial. Methods: In a multi-institutional study, we included 66 patients treated with cabazitaxel after docetaxel for mCRPC. Patients were stratified according to the two- and three-risk groups of the Halabi nomogram. Kaplan-Meier and Cox proportional hazard analyses were performed to estimate survival and hazard ratios (HRs). The model performance was assessed using receiver operating characteristic curves, and the associated c-index (area under the curve [AUC]). Results: The median OS in the two-risk groups was 5.06 months in the high-risk group (n=22) and 12.9 months in the low-risk group (n=44, p<0.001). High-risk patients had an HR of 9.50 (95% confidence interval (CI) 4.12-21.6, p<0.001) compared to low-risk patients. For the three-risk groups, the median OS was 6.44 months in the high-risk group (n=15), 5.75 months in the intermediate-risk group (n=11), and 13.7 months in the low-risk group (n=40, p=0.84). Compared to low-risk patients, intermediate-risk patients had an HR of 7.49 (95% CI 3.08-20.4, p<0.001), and high-risk patients had an HR of 8.48 (95% CI, 3.39-21.7, p<0.001). The AUC was 0.72 (95% CI 0.64-0.76) for the two-risk stratification. When comparing different risks, the AUCs were 0.48 (high vs intermediate), 0.66 (high vs low), and 0.65 (intermediate vs low). Conclusions: The two-risk stratification version but not the three-risk group analysis confirmed the ability of the model to predict survival. These results support the value of the Halabi nomogram in men receiving post-docetaxel second-line chemotherapy for mCRPC.

Efficacy and safety of cabazitaxel therapy in elderly (≥75 years) patients with castration-resistant prostate cancer: A multiinstitutional study.

BACKGROUND: There is little data on the outcome of cabazitaxel (CBZ) treatment of elderly patients with castration-resistant prostate cancer (CRPC). This study assessed the efficacy and safety of CBZ chemotherapy in patients with CRPC aged 75 years or older in a multiinstitutional study. METHODS: We retrospectively reviewed the 74 patients with CRPC treated with CBZ enrolled in 10 institutions. Clinicopathological backgrounds, prognosis including prostate-specific antigen decline, time to treatment failure, progression-free survival, overall survival, and safety profiles were compared between younger (<75 years) and elder (≥75 years) patients. RESULTS: In total, 74 patients were enrolled; 50 patients were younger than 75 years and 24 were ≥75 years. Clinicopathological characteristics were comparable between younger and elder patients, with the exception of serum albumin values at the time of CBZ treatment. The median prostate-specific antigen decline in younger and elder men was -8.8% and -32.3% from baseline, respectively. The median time to treatment failure, progression-free survival, and overall survival for younger and elder men were 0.24 and 0.33 years, 0.23 and 0.43 years, and 0.69 and 1.17 years, respectively. In addition, safety profiles were comparable between younger and elder patients. CONCLUSIONS: This multiinstitutional study suggests that patients with CRPC aged 75 years or older eligible for CBZ treatment can be treated safely and with noninferior efficacy compared with those younger than 75 years.

Prognostic significance of lactate dehydrogenase in cabazitaxel chemotherapy for castration-resistant prostate cancer: a multi-institutional study.

This multi-institutional study aimed to identify prognostic factors for cabazitaxel treatment of castration-resistant prostate cancer (CRPC). This study included 74 Japanese patients with CRPC who were treated with cabazitaxel between 2014 and 2017. Associations between clinicopathological factors including serum markers and progression-free survival (PFS) and overall survival (OS) were investigated. On multivariate analysis, high Gleason score [≥9 vs. ≤7; hazard ratio (HR), 95% confidence interval (CI): 2.00 (1.01-4.34); P = 0.047], presence of pain [HR, 95% CI: 2.02 (1.14-3.58); P = 0.016], and lactate dehydrogenase (LDH) level [HR, 95% CI: 47.31 (3.79-577.49); P = 0.0019] were significantly associated with PFS. Similarly, number of docetaxel cycles [HR, 95% CI: 0.050 (0.0037-0.45); P = 0.0057], performance status [≥2 vs. 0; HR, 95% CI: 5.07 (1.57-16.24); P < 0.0001], and LDH level [HR, 95% CI: 2946 (50-420994); P = 0.0001] were significantly associated with OS. This study showed that LDH level is robustly prognostic for both PFS and OS in cabazitaxel chemotherapy for CRPC.

Prognostic Impact of Prior Androgen Receptor Axis-targeting Agents in Cabazitaxel Chemotherapy After Docetaxel.

BACKGROUND/AIM: The novel taxane cabazitaxel has been shown to exert excellent anticancer effects after androgen receptor axis-targeting (ARAT) agents in clinical data, but not in in vitro data. We investigated the clinical outcome of cabazitaxel chemotherapy after docetaxel according to use of ARAT agents. PATIENTS AND METHODS: Prostate specific antigen (PSA) response, progression-free survival, and overall survival were compared between cases with and without prior use of ARAT agents in 74 Japanese patients with metastatic castration-resistant prostate cancer treated with cabazitaxel chemotherapy. RESULTS: Background characteristics were comparable between patients with and without prior use of ARAT agents. PSA response, progression-free survival, and overall survival in cabazitaxel chemotherapy were comparable between patients with and without prior use of ARAT agents. CONCLUSION: No detrimental effects of prior ARAT agents on clinical outcome were observed for cabazitaxel chemotherapy in the post-docetaxel setting, suggesting that cabazitaxel can be expected to remain active even after ARAT agent therapy.

Therapeutic Outcome of >10 Cycles of Cabazitaxel for Castration-resistant Prostate Cancer: A Multi-institutional Study.

BACKGROUND/AIM: Cabazitaxel use has usually been limited to up to 10 cycles in most countries according to the protocol in the TROPIC trial. Therefore, clinical data on cabazitaxel use beyond 10 cycles is limited. The aim of this study was to report the therapeutic outcome of cabazitaxel chemotherapy administered for >10 cycles. PATIENTS AND METHODS: This study included 74 Japanese patients with prostate cancer between 2014 and 2017. Patients background, and treatment outcomes including PSA decline, progression-free survival, treatment-failure-free survival, overall survival, and adverse events were investigated, comparing patients treated with ≤10 and >10 cycles. RESULTS: Patients characteristics were favorable as indicated by the higher number of cycles of prior docetaxel chemotherapy, absence of pain, and absence of bony and visceral metastases among men who received >10 cycles of cabazitaxel. PSA response, progression-free survival, treatment-failure-free survival and overall survival were better among patients treated with >10 cycles of cabazitaxel compared to those treated with ≤10 cycles. The incidence of severe adverse events was similar between the two groups. CONCLUSION: Taken together, this study suggested that continuous chemotherapy with cabazitaxel beyond 10 cycles may be beneficial.

Efficacy and safety of 4-weekly cabazitaxel for castration-resistant prostate cancer: a multi-institutional study.

OBJECTIVE: This study aimed to reveal the efficacy and safety profiles of 4-weekly cabazitaxel in patients with castration-resistant prostate cancer (CRPC). METHODS: The study included 62 Japanese patients who were treated for CRPC with ≥ 2 courses of cabazitaxel between 2014 and 2017. The oncological outcomes and adverse events were compared between 16 (25.8%) and 46 (74.2%) men who were treated with standard 3-weekly and alternative 4-weekly regimens, respectively. RESULTS: The prostate-specific antigen (PSA) response was comparable between the 3-weekly and 4-weekly regimens (median [interquartile range]: - 9.9% [- 64.5 to 13.0%] and - 30.7% [- 52.8 to 10.9%], P = 0.89), respectively. For patients on the 4-weekly regimen, the risks of progression (hazard ratio [HR], 95% confidence interval [CI] 1.27, 0.71-2.43, P = 0.44), treatment failure (HR, 95% CI 0.84, 0.48-1.55, P = 0.57) and any-cause mortality (HR, 95% CI 1.09, 0.58-2.17, P = 0.79) were comparable to those for patients on the 3-weekly regimen. The incidences of severe adverse events were also similar between the 3-weekly and 4-weekly regimens. CONCLUSIONS: 3-weekly and 4-weekly regimens of cabazitaxel showed similar efficacy and safety profiles in a real-world clinical setting. These data suggest that a 4-weekly regimen may be acceptable for selected patients.

Efficacy and safety of cabazitaxel for castration-resistant prostate cancer in patients with > 10 cycles of docetaxel chemotherapy: a multi-institutional study.

This multi-institutional study aimed to investigate the efficacy and safety profiles of cabazitaxel after prior docetaxel chemotherapy in patients with castration-resistant prostate cancer (CRPC). This study included 63 Japanese patients with CRPC who were treated with cabazitaxel from 2014 to 2017. The oncological outcomes and adverse events (AEs) were documented, and prognostic factors for oncological outcomes and predictive factors for AEs were analysed. PSA decline was observed in 68.3% of patients, including 25.4% who achieved a ≥ 50% decline. The median progression-free survival, treatment failure-free survival, and overall survival were 4.3, 4.1, and 9.0 months, respectively. More cycles of prior docetaxel therapy was identified as common favourable prognostic factors for progression-free survival, treatment failure-free survival, and overall survival. Severe neutropenia, febrile neutropenia, and severe non-haematological AEs were observed in 73.0%, 33.3%, and 23.8% of patients, respectively. However, > 10 cycles of docetaxel was not associated with increased incidence of AEs. In conclusion, cabazitaxel chemotherapy was still active in Japanese CRPC patients treated with > 10 cycles of docetaxel chemotherapy, with an acceptable risk of AE burden. Treatment with cabazitaxel after > 10 cycles of docetaxel may be an appropriate option when it can be administered.

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.

A pilot study of the assessment of the quality of life, functional results, and complications in patients with an ileal neobladder for invasive bladder cancer.

OBJECTIVE: To assess the functional results, health-related quality of life (QOL) outcomes, and complications in patients with an ileal neobladder in comparison to those with cutaneous diversion (ileal conduit and cutaneostomy). METHODS: Between September 1992 and February 2003, we consecutively performed an ileal neobladder (the Studer method) in 30 patients and cutaneous diversion in 38 patients. In August 2004, questionnaires were mailed to 54 patients. The questionnaire included the validated health-related quality of life (QOL) questionnaire, SF-36 General Health Survey, and a urinary incontinence questionnaire. We also evaluated the functional results in patients with an ileal neobladder and the postoperative complications in patients with both urinary diversions. RESULTS: The data from 41 patients (21 ileal neobladder procedures and 20 cutaneous diversions) were available for the analysis. No differences in the overall QOL were observed between the two groups. Complete daytime and night-time urinary continence was achieved in the 21 patients (100%) and 13 patients (61.9%), respectively. The mean value of the maximum flow rate was 15 +/- 12 mL/min in the 21 neobladder patients. There were 19 early complications in 18 patients (60.0%) and seven late complications in six patients (20.0%) with an ileal neobladder. However, there were 15 early complications in 14 patients (36.8%) and eight late complications in six patients (15.8%) with cutaneous diversions. CONCLUSION: The findings regarding the health-related QOL and the frequency of complications in the neobladder group and those in the cutaneous diversion group were similar. However, the functional results and the status of urinary continence in the neobladder patients were satisfactory.

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.

Clinical outcomes and learning curve of a laparoscopic adrenalectomy in 103 consecutive cases at a single institute.

OBJECTIVE: We examined the clinical outcomes and the learning curve for a laparoscopic adrenalectomy (LA) in 103 consecutive cases performed by three surgeons at our institute, according to the type of adrenal disorder. PATIENTS AND METHODS: One hundred and three patients with adrenal tumors, including 38 cases of primary aldosteronism, 33 cases of Cushing syndrome (including preclinical Cushing syndrome), 15 cases of pheochromocytoma, and nine cases of non-functioning adenoma were evaluated, while focusing on the approaches, intraoperative and postoperative data, and the learning curve of LA, according the type of adrenal disorder. RESULTS: There was no significant difference in the operation time, estimated blood loss, incidence of conversion to open surgery and blood transfusion, or postoperative recovery among the patients treated by LA for aldosteronoma, Cushing adenoma, pheochromocytoma, and non-functioning adenoma. In the cases of aldosteronoma and Cushing adenoma, the learning curve for the operation time and blood loss in each operator tended to decrease as the number of operations increased. On the other hand, in the cases treated by LA for pheochromocytoma, no trends in either the operation time or blood loss were observed. However, there has been neither any conversion to open surgery nor blood transfusion in cases treated by LA since 1998 (our 42nd case), even after the changes in the operators. CONCLUSIONS: Our results clearly indicate that LA is becoming safer than before, probably due to improvements in the technique, education, and training of surgeons, in addition to the increased number of cases now treated by LA.

Renal cancer treatment with low levels of mixed chimerism induced by nonmyeloablative regimen using cyclophosphamide in mice.

Recently, much attention has been paid to nonmyeloablative allogeneic stem cell transplantation for the treatment of metastatic renal cancer. Mature donor T cells cause graft-versus-host disease (GVHD) although they are also the main mediators of the beneficial graft-versus-tumor activity associated with this treatment. Hence, the segregation of the graft-versus-tumor activity from GVHD is an important challenge in managing the clinical course of treatment. We previously reported a series of studies regarding the allograft tolerance induced by allogeneic spleen cells (with bone marrow cells) and cyclophosphamide in mice. Here, we show a modified cyclophosphamide-induced tolerance system for the treatment of murine renal cell carcinoma, RENCA, by shifting the equal balance between graft-versus-host and host-versus-graft reactions toward graft-versus-host reaction with donor lymphocyte infusion. Our results clearly show the antitumor activity against RENCA with only low levels of mixed chimerism in the periphery and the in vivo and in vitro acquired immunity against RENCA even when mixed chimerism is almost undetectable. Because the withdrawal of mixed chimerism reduces the risk of GVHD, the antitumor activity is thus sequentially segregated from the initial GVHD in our model. We believe that this is the first unique model system of nonmyeloablative allogeneic hemopoietic cell transplantation to ever be reported for the treatment of renal cancer.