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.     

Analysis of effectiveness of therapeutic exercise for knee osteoarthritis and possible factors affecting outcome

Background

There are numerous reports and evidences to suggest that exercise therapy is effective for knee osteoarthritis (knee OA). However, there is a lack of sufficient research concerning the factors influencing its application and effectiveness. The purposes of this study were to evaluate effects of the mode of treatment delivery on the improvement of symptoms in knee OA, and to analyze potential risk factors affecting improvement after exercise therapies.

Methods

The 209 women applicants diagnosed with knee OA were randomly allocated into either a group performing group exercise in a class or a group performing home exercise. The 90 min exercise program was performed under the guidance of physiotherapists as a group exercise therapy. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) of the subjects of both groups before and after intervention was compared to examine the effect of exercise therapy. In addition, body mass index, knee range of motion (ROM), the femorotibial angle from radiographs, OA severity from Kellgren–Lawrence grade, and meniscus abnormality and subchondral bone marrow lesions from MRI findings were statistically analyzed as factors that may affect exercise therapy.

Results

A significantly greater improvement in WOMAC was observed in the subjects of group exercise (81 subjects) as compared with the subjects of home exercise (122 subjects). There was a significantly high proportion of subjects with knee flexion contracture among the subjects participating in group exercise that showed only minor symptom improvement (p < 0.05). In addition, exercise therapy proved to be highly effective for subjects with limited quadriceps muscle strength (p < 0.05).

Conclusions

When prescribing exercise therapy for knee OA, evaluation of a subject’s ROM and muscle strength is important in deciding whether to commence exercise therapy and what type of exercise therapy to apply; it is also important in predicting the effect of exercise therapy.     

Endoscopic far-lateral approach to the posterolateral craniovertebral junction: an anatomical study

Minimally invasive surgery to the posterolateral craniovertebral junction (CVJ) has not been sufficiently described. The aims of this study were to evaluate the feasibility of an endoscopic far-lateral approach to the posterolateral craniocervical junction and to better understand the related anatomy under distorted endoscopic view. Ten fresh cadavers were studied with 4-mm 0° and 30° endoscopes to develop the surgical approach and to identify surgical landmarks. After making a 3-cm straight incision behind the mastoid process, the superior oblique and rectus capitis posterior major muscles were partially exposed. An endoscope was then introduced and the two muscles were followed inferiorly until the posterior arch of the atlas appeared. The two muscles were removed to create ample working space without violating the posterior atlanto-occipital membrane. The vertebral artery was identified by the landmark of the posterior arch of the atlas, and the atlanto-occipital joint and foramen magnum were exposed. In addition to suboccipital craniectomy, transcondylar, supracondylar, and paracondylar extension by drilling were applicable through the narrow corridor under superb visualization. The intradural neurovascular structures from the acousticofacial bundle to the dorsal root of C2, anterolateral space of the foramen magnum, cerebellomedullary fissure, and fourth ventricle were clearly demonstrated. This endoscopic far-lateral approach offers excellent exposure of surgical landmarks around the posterolateral CVJ with minimal invasiveness. Endoscopic soft tissue dissection is key to creating the surgical corridor. This approach could offer an alternative to the conventional far-lateral approach in selected cases.     

Evidence of the extrathymic development of tyrosinase-related protein-2-recognizing CD8+ T cells with low avidity

The majority of the human tumour‐associated antigens characterized to date are derived from non–mutated self‐proteins. However, nothing is known about the development of autoreactive and tumour‐associated antigen‐recognizing T cells. Tyrosinase‐related protein (TRP)‐2 is a non‐mutated melanocyte differentiation antigen and TRP‐2‐recognizing CD8⁺ T cells are known to show responses to melanoma both in humans and mice. In addition, TRP‐2‐reactive T cells with low avidity have been suggested to be readily induced from the spleen cells of naïve mice. On the other hand, recent reports suggest that self antigen‐reactive CD8⁺ T cells can be positively selected in the periphery. In this study, we tested the possibility that TRP‐2‐reactive CD8⁺ T cells in naïve mice could develop via the extrathymic pathway. As a consequence, TRP‐2‐reactive CD8⁺ T cell precursors in naïve C57BL/6 mice were suggested to express both interleukin‐2 (IL‐2) receptor β chain (IL‐2Rβ) and CD44 molecules, in a manner similar to that of extrathymically developed T cells. Furthermore, IL‐2Rβ⁺ CD44⁺ CD8⁺ T cells were detected in the adult thymectomized and bone marrow‐reconstituted mice, and functional TRP‐2‐reactive T cells were generated from their spleen cells. Overall, these results suggest that low avidity CD8⁺ T cells recognizing TRP‐2 can be developed extrathymically.     

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.     

Inhibitory Effect of a Traditional Chinese Medicine, Juzen-taiho-to, on Progressive Growth of Weakly Malignant Clone Cells Derived from Murine Fibrosarcoma

We have investigated the inhibitory effect of oral administration of Juzen-taiho-to , a Kampo (Chinese herbal) medicine, on progressive growth of a mouse fibrosarcoma. Spontaneously regressive QR-32 tumor cells were able to grow progressively in vivo when coimplanted s.c. with a foreign body, gelatin sponge, whereas QR-32 cells alone gradually grew for over 15 days after inoculation and thereafter regressed for up to 25 days. Oral administration of Juzen-taiho-to (40 mg/day/mouse) for 7 days after inoculation of QR-32 cells with gelatin sponge resulted in significant inhibition of tumor growth and prolongation of the survival of the tumor-bearing mice. This growth-inhibitory effect of Juzen-taiho-to observed on day 25 was dose-dependent over the dose range from 4 to 40 mg/day. Treatment with Juzen-taiho-to for 7 days before tumor inoculation with gelatin sponge also significantly suppressed tumor growth examined on day 25, as did the administration of bismuth subnitrate, which is well known to induce metallothionein, an antioxidant. On the other hand, inoculation of progressed tumor cells (QRsP) resulted in growth without gelatin sponge, leading to death in syngeneic mice. Administration of Juzen-taiho-to for 7 days after inoculation of QRsP cells resulted in a decrease of the tumor growth and prolongation of the survival of mice, but the effect was less than that on the growth of QR-32 regressor tumor after coimplantation with gelatin sponge. These results suggest that the inhibitory effect of Juzen-taiho-to is partly associated with prevention of gelatin sponge-elicited progressive growth, probably mediated by endogenous factors including antioxidant substances, in addition to the augmentation of host-mediated antitumor activity.     

Long-term outcome of hand-assisted laparoscopic radical nephrectomy for localized stage T1/T2 renal-cell carcinoma

PURPOSE: To evaluate the efficacy of hand-assisted laparoscopic radical nephrectomy (HALRN) in patients with localized stage T(1)/T(2) renal-cell carcinoma, we analyzed the clinical results of our patients treated in this way. PATIENTS AND METHODS: From March 1999 to March 2003, a total of 96 patients aged 28 to 86 years (mean 61 years) with clinical stage T(1)/T(2)N(0)M(0), pathologically confirmed renal-cell carcinoma underwent HALRN. The outcomes were compared with those of open radical nephrectomy, which was performed in 86 patients from November 1991 to February 1999 in our institution. Kaplan-Meier analysis was used to analyze survival. RESULTS: Ten patients (10.4%) had perioperative complications. During a mean follow-up of 25 months (range 6-54 months), no patients died of the cancer, although three patients had metastatic disease. The 4-year disease- free and overall survival rates were 88% and 100%, respectively. Seventy-eight patients who underwent open radical nephrectomy were followed for 38 to 156 months (median 86 months). Seventy-three survived without any recurrent disease, five survived with metastasis, and no patient died of metastatic disease. The 4-year disease-free and overall survival rates were 93% and 100%, respectively. CONCLUSIONS: Hand-assisted laparoscopic surgical management of T(1)/T(2) renal-cell carcinoma is feasible and safe. At our institution, HALRN confers long-term oncologic effectiveness equivalent to that of open radical nephrectomy.