Updated long-term outcomes after carbon-ion radiotherapy for primary renal cell carcinoma.

Long-term oncological outcomes for primary renal cell carcinoma (RCC) treated with carbon-ion radiotherapy (CIRT) are poorly understood. Patients with primary RCC were treated with 12 or 16-fraction CIRT at The Hospital of the National Institute of Radiological Sciences outside of clinical trials. Outcome data were pooled and retrospectively analyzed for toxicity, local control, and disease-free, cancer-specific, and overall survival. From 1997 to 2014, 19 RCC patients (11 with T1aN0M0, 4 with T1bN0M0, and 4 with inoperable advanced stage [T4N0M0, T3aN1M0, and T1aN0M1]) were treated with CIRT and followed up for a median of 6.6 (range, 0.7-16.5) years; 9 of these patients were inoperable because of comorbidities or advanced-stage disease. Diagnoses were confirmed by imaging in 11 patients and by biopsy in the remaining 8. In 4 of 5 patients with definitive renal comorbidities, including diabetic nephropathy, sclerotic kidney or solitary kidney pre-CIRT progressed to grade 4 chronic kidney disease (CKD). In contrast, the remaining 14 patients without definitive renal comorbidities did not progress to grade 3 or higher CKD. Furthermore, although 1 case of grade 4 dermatitis was observed, there were no other grade 3 or higher non-renal adverse events. Local control rate, and disease-free, cancer-specific, and overall survival rates at 5 years of all 19 patients were 94.1%, 68.9%, 100%, and 89.2%, respectively. This updated retrospective analysis based on long-term follow-up data suggests that CIRT is a safe treatment for primary RCC patients without definitive renal comorbidities pre-CIRT, and yield favorable treatment outcomes, even in inoperable cases.

Ergonomic design and evaluation of new surgical scissors.

The purpose of this study is to design a new surgical scissors handle and determine its effectiveness with various usability indices. A new scissors handle was designed that retains the professional grip but has the shapes of the eye rings modified to fit the thumb and ring finger and finger rests for the index and little finger. The newly designed scissors and traditional scissors were compared by electromyography, subjective evaluation and task performance in experiments using cutting and peeling tasks. The newly designed scissors reduced muscle load in both hand during cutting by the closing action, and reduced the muscle load in the left hand during peeling by the opening action through active use of the right hand. In evaluation by surgeons, task performance improved in addition to the decrease in muscle load. The newly designed scissors used in this study demonstrated high usability. PRACTITIONER SUMMARY: A new scissors handle was designed that has the eye rings modified to fit the thumb and ring finger. The newly designed scissors reduced muscle load and enabled active use of the right hand. In evaluation by surgeons, task performance improved in addition to the decrease in muscle load.

Therapeutic designing for urethral obstruction by virtual urethra and flow dynamics simulation.

INTRODUCTION: Transurethral surgery is widely accepted as standard therapy for male urethral obstruction. The present study was undertaken to identify and select lesions to be managed by processing endoscopic images of the urethra for assisting less invasive therapy in patients with voiding dysfunction. MATERIAL AND METHODS: Cystourethroscopic video files of 25 patients with lower urinary tract symptoms were recorded before and after administration of alpha-1 adrenoceptor antagonists. Each video frame was restored and tagged with information indicating the position in the panoramic image of the urethra. A three-dimensional virtual urethra was created to indicate critical lesions for voiding dysfunction, together with fluid dynamics simulation of urine flow. RESULTS: The urine stream was depicted in the virtual urethras in 19 patients. Before therapy, 17 patients showed vortex formation that was diminished after therapy in nine patients with a significant relationship in improvement of relative energy loss of flow (p=0.025). The narrowing points proximal to the vortex, candidate of lesions, were identified in the panoramic image and linked to the endoscopic image. DISCUSSION: Therapeutic designing for endoscopic management was possible in patients with voiding dysfunction based on computational fluid dynamics, and would be promising as "focal" therapy for aging males.

Effects of chamber shapes on maneuverability and control property of endoscope-support soft actuators.

Introduction: Minimally Invasive Surgery (MIS) offers targeted surgical access with reduced invasiveness; however, the maneuverability challenges of traditional instruments in this domain underscore the need for innovative solutions. Soft actuators activated by fluids or gases present a promising strategy for augmenting endoscopic capabilities, thereby enhancing the surgical precision in MIS. This study aimed to explore the intricate dynamics of the interactions between soft actuators and endoscopes, with an emphasis on the pivotal role of cross-sectional chamber shapes. While previous studies have touched on the influence of chamber shapes on bending properties, we provide a comprehensive exploration. We explore how these shapes modulate friction forces, which in turn influence the interactions governing bending, response, and stiffness adjustability, all of which are essential for enhancing endoscope maneuverability in MIS contexts. Methods: A novel bilateral symmetrical air chamber design was adopted to investigate various chamber shapes. We employed finite element analysis (FEA) simulations followed by prototype testing to evaluate the interactions driven by these chamber shapes and to discern their impact on actuator properties. Recognizing the pivotal role of friction in these interactions, we conducted dedicated friction experiments. These experiments further deepened our understanding of the relationship between chamber shape and friction, and how this synergy influences the properties of the actuator. Results: Our findings showed that actuators with wider chambers generate larger friction forces, thereby enhancing the interaction and improving the bending, response, and stiffness adjustability. Additionally, the soft actuator significantly improved the maneuverability and bending radius of the endoscope, demonstrating enhanced navigation capabilities in complex environments. Discussion: The shape of a cross-sectional chamber plays a pivotal role in designing soft actuators for MIS applications. Our research emphasizes the importance of this design component, offering key insights for the development of endoscope-supporting soft actuators that can effectively handle intricate actuator-endoscope interactions, thereby enhancing surgical outcomes.

[A case of favorable response after combination treatment with interferon-α and cyclooxygenase-2 inhibitor against metastatic renal cell carcinoma].

We present a patient showing favourable response after combination treatment with interferon-α (IFN- α) and cyclooxygenase-2 (Cox-2) inhibitor (celecoxib) against metastatic renal cell carcinoma (RCC). The patient underwent left radical nephrectomy for RCC on 18th April, 2005. On follow-up computed tomographic scan, mediastinal metastasis was detected 3 years after nephrectomy, and metastasectomy was performed. The histological features were clear cell carcinoma as was the primary RCC, and immunohistochemical analysis revealed negative for Cox-2 staining both the primary and metastatic lesions. Aiming at the treatment of residual mediastinal RCC, the patient started to receive IFN-α, and this cytokine therapy lasted for 1 year and 2 months. Nevertheless, the outcome was progression of disease (PD), namely, new lung field lesions were observed. A different type of IFN-α treatment also resulted in PD. Based upon these results, a combination of IFN-α and Cox-2 inhibitor was newly adopted for treatment. After the combination therapy for 3 months, 68.75% of metastases disappeared. We concluded that Cox-2 inhibitor is a potent medicine in combination with IFN-α for metastatic lung tumour from RCC.

Influence of visceral obesity on oncologic outcome in patients with renal cell carcinoma.

OBJECTIVE: At present, computed tomography (CT) is used in almost all patients with renal tumors. We aimed to investigate the relationship between visceral adipose tissue (VAT), as assessed by CT, and various other factors in patients with renal cell carcinoma (RCC). METHODS: We undertook an examination of VAT in 117 male patients undergoing nephrectomy or partial nephrectomy at Chiba University Hospital using software designed to detect VAT in the horizontal plane of the body cavity. Pathological stage, microvascular invasion, tumor grade, performance status, C-reactive protein, BMI, hypertension, hyperlipemia, hyperglycemia, history of smoking and cause-specific survival rate were examined in relation to VAT, and multivariate Cox regression analysis was used to determine significant predictors of cause-specific survival. RESULTS: VAT in patients with stage I disease was significantly greater than that in patients with more advanced disease (p = 0.0219). VAT in patients with microvascular invasion was significantly smaller than in those without microvascular invasion (p = 0.0260). Patients with high VAT had significantly higher cumulative cause-specific survival when compared to patients with low VAT (p = 0.0257). CONCLUSION: VAT was associated with better clinical features in patients with RCC. Further study is necessary in order to clarify the role of VAT in RCC.

The future of urodynamics: non-invasive ultrasound videourodynamics.

A totally non-invasive transperineal urodynamic technique using Doppler ultrasonography has been developed. Normal urine doesn't have blood cells so urine was thought not to produce Doppler effects. However, basic studies confirmed that the decrease of pressure at high velocity (Bernoulli effects) caused dissolved gas to form microbubbles, which are detected by Doppler ultrasonography. Subjects sat and a probe was advanced via remote control to achieve gentle contact with the perineal skin. The digital uroflow data signals and the color Doppler ultrasound video images were processed on a personal computer. This method was viable to diagnose the degree of bladder outlet obstruction. The advantage of being rapid, effective, and equipped with no special attachments allows it to surpass any other non-invasive urodynamic methods. The difference between the echocardiogram and the ultrasound urodynamic system is only the frequency of obtaining velocity information: more than 50 times per minute vs once every several hours, respectively. Although the ultrasound urodynamic system is more difficult to develop than the echocardiogram, one principle is shared by both methods. The patient can void freely without interruptions, there is no contact between the penis and the equipment and it is specifically directed toward non-invasive diagnosis. The development of non-invasive Doppler ultrasound videourodynamics will dramatically expand understanding of voiding function.

Computer-based endoscopic image-processing technology for endourology and laparoscopic surgery.

Endourology and laparoscopic surgery are evolving in accordance with developments in instrumentation and progress in surgical technique. Recent advances in computer and image-processing technology have enabled novel images to be created from conventional endoscopic and laparoscopic video images. Such technology harbors the potential to advance endourology and laparoscopic surgery by adding new value and function to the endoscope. The panoramic and three-dimensional images created by computer processing are two outstanding features that can address the shortcomings of conventional endoscopy and laparoscopy, such as narrow field of view, lack of depth cue, and discontinuous information. The wide panoramic images show an anatomical 'map' of the abdominal cavity and hollow organs with high brightness and resolution, as the images are collected from video images taken in a close-up manner. To assist in laparoscopic surgery, especially in suturing, a three-dimensional movie can be obtained by enhancing movement parallax using a conventional monocular laparoscope. In tubular organs such as the prostatic urethra, reconstruction of three-dimensional structure can be achieved, implying the possibility of a liquid dynamic model for assessing local urethral resistance in urination. Computer-based processing of endoscopic images will establish new tools for endourology and laparoscopic surgery in the near future.

Usefulness of panoramic views for novice surgeons doing retroperitoneal laparoscopic nephrectomy.

OBJECTIVES: Laparoscopic surgery is widely accepted for managing renal disease. Thus, the system used to educate and train novice surgeons in laparoscopic surgery becomes important to reduce the risks of surgery during their training. A prospective study was carried out to determine the usefulness of using panoramic views during laparoscopic surgery. METHODS: Between April 2004 and March 2007, four novice surgeons started learning laparoscopic radical nephrectomy: two carried out surgery without panoramic views and two used panoramic views. Operating time and blood loss for the initial 10 cases of each surgeon were compared. Panoramic views were obtained by interlacing each video frame of the video images electronically; the images were then processed and displayed during each step of laparoscopic surgery. RESULTS: Panoramic, real-time views could be obtained, and they served as navigation maps. The learning curve of surgeons using the panoramic views was shorter than that of surgeons who did not use panoramic views. Time to ligation of renal artery from port placement and the operating time was shorter (69.0 +/- 21.5 min vs 106.8 +/- 44.9 min, P = 0.0016, 212 +/- 42 min vs 254 +/- 46 min, P = 0.0489, respectively) and the estimated blood loss was less for the surgeons who used panoramic views (87 +/- 109 mL vs 334 +/- 268 mL, P = 0.0005). CONCLUSION: Panoramic views during laparoscopic surgery shortened operating time and reduced blood loss, indicating their usefulness in assisting novice surgeons to carry out procedures safely and accurately.

[Case of retroperitoneal fibrosis after surgical treatment of autoimmune pancreatitis].

We present a case of retroperitoneal fibrosis (RPF) in a 72-year-old man who previously received pancreatectomy for autoimmune pancreatitis. He had received colectomy for early colon cancer on 11th November, 2005. During the routine follow-up for colon cancer, a swollen pancreas tail was detected on enhanced CT. He received distal pancreatectomy under the diagnosis of pancreas cancer on 4th October, 2007. Pathological diagnosis revealed the autoimmune pancreatitis. Eight months later, right hydronephrosis was observed in an abdominal ultrasonographic study, and at the same time, right hydroureterosis due to retroperitoneal soft tissue mass around the bifurcation was detected on enhanced CT. He was treated with predonisolone aiming at the diagnosis and/or therapy. Twelve weeks later, right hydronephrosis had disappeared and retroperitoneal mass had shrunken. Now, it is thought that autoimmune pancreatitis is a systemic sclerosing disease accompanied with extra-pancreatic pathologic changes such as RPF.

Prospective clinical trial of 12-fraction carbon-ion radiotherapy for primary renal cell carcinoma.

The aims of this study were to clarify the safety and efficacy of 12-fraction carbon-ion radiotherapy (CIRT) for primary renal cell carcinoma (RCC) and to confirm the recommended dose in a prospective clinical trial. This clinical trial was planned as a non-randomized, open-label, single-center phase I/II study of CIRT monotherapy. The incidence of acute adverse events was the primary endpoint. Dose-limiting toxicities (DLTs) were defined as grade ≥3 skin, gastrointestinal tract, or urologic adverse events. Based on the eligibility criteria, 8 patients with primary RCC, including 3 medically inoperable patients and 5 patients with tumors >4 cm, were enrolled. Of the 8 patients, 5 were treated with 66 Gy (relative biological effectiveness [RBE]), and subsequently, the dose was escalated to 72 Gy (RBE) for the remaining 3 patients. The median follow-up time was 43.1 months. No DLTs were observed at any dose level though the end of follow-up. Although 1 patient died of pneumonia 3 months after CIRT, which was determined to be unrelated to CIRT, no grade 3 or higher adverse events were observed, and both local control and cancer-specific survival rates were 100%. In conclusion, the safety and efficacy of CIRT hypofractionation using 12-fractions for the treatment of eligible RCC patients, including those with inoperable or tumor size >4 cm, were confirmed in this prospective trial, and a recommended dose of 72 Gy (RBE) was established.

[Study on the diagnosis of urothelial cancer using multi-colour fluorescence in situ hybridization (FISH)--comparative analysis between FISH and cytology].

To determine the diagnostic merit or demerit of genetic procedures using fluorescence in situ hybridization (FISH) for detecting both new and recurrent urothelial cancer, we analyzed the specimens from 81 out-patients with asymptomatic haematuria, aged over 40, in comparison with urine cytology. Of 10 with atypical cytology, 6 showed positive for FISH, and of these, 4 manifested urothelial cancer. FISH showed higher sensitivity in low/intermediate grade cases compared with cytology (FISH; 66.7% vs cytology; 11.1%). Of 15 primary bladder cancer, 4 showed recurrence, and all of these cases showed a positive FISH reaction, but only 1 in cytology. The sensitivity, specificity and accuracy of FISH tests were 81.2, 72.3 and 74.1%, respectively, and these of cytology were 37.5, 98.5 and 86.4% respectively. The FISH test was superior to cytology for sensitivity, but specificity and accuracy were inferior. The FISH tests could be a potent procedure for detecting urothelial cancer in cases of low/intermediate grade, atypical cytology and surveillance setting.

[A case report of chromophobe cell renal carcinoma arising from atrophic kidney during long-term haemodialysis].

A 60-year-old woman with chromophobe cell renal carcinoma arising from the atophic right kidney during long-term haemodialysis was reported. The right renal tumour was detected incidentally by abdominal ultrasound examination. She received right nephrectomy through flank incision, and the pathological diagnosis was an eosinophilic variant of chromophobe cell renal carcinoma. Chromophobe cell renal carcinoma is a relatively rare subtype of renal cell carcinoma (5%), and the rate of this subtype on a long-term haemodialysis was quite low (0.6-0.7%), and almost all these patients had acquired cystic disease accompanied with haemodialysis. By contrast, our case occurred in the atrophic kidney (non-cystic kidney), and this might be the first case report of chromophobe cell renal carcinoma arising from an atrophic kidney in a patient on long-term haemodialysis.

Physiological and Biochemical Responses to Continuous Saline Irrigation Inside the Abdominal Cavity in Anesthetized Pigs.

BACKGROUND: Water-filled laparoendoscopic surgery (WaFLES) has been proposed as a novel surgical system achieving a wide surgical field in the intra- and extraperitoneal space with continuous irrigation of isotonic fluid into the field. Despite its technical feasibility and advantages, the safety of the technique, particularly with respect to physiological functions, has not been evaluated. METHODS: Various types of minor abdominal surgeries were performed under general anesthesia in nine adult pigs either by conventional laparoscopy (n = 3) or WaFLES (n = 6). In addition to esophageal temperature and body weight, cardiorespiratory variables such as blood pressure, heart rate, and arterial blood gas parameters were compared before and after the surgeries. Blood samples were obtained for assessing changes in biochemical parameters before and after the surgeries. RESULTS: Three to seven hours of various surgeries were completed without critical cardiorespiratory events in all animals. Oxygenation and ventilation were maintained regardless of the techniques used for the surgeries. A minor increase of body weight (2.5% of initial body weight), metabolic acidosis, hyperkalemia, and impaired hepatic function were observed after WaFLES surgeries. CONCLUSIONS: The preliminary study indicated no serious immediate adverse effects of the WaFLES technique.

Small-Incision Laparoscopy-Assisted Surgery Under Abdominal Cavity Irrigation in a Porcine Model.

BACKGROUND: Laparoscopic and robot-assisted surgeries are performed under carbon dioxide insufflation. Switching from gas to an isotonic irrigant introduces several benefits and avoids some adverse effects of gas insufflation. We developed an irrigating device and apparatus designed for single-incision laparoscopic surgery and tested its advantages and drawbacks during surgery in a porcine model. MATERIALS AND METHODS: Six pigs underwent surgical procedures under general anesthesia. A 30-cm extracorporeal cistern was placed over a 5-6-cm abdominal incision. The abdomen was irrigated with warm saline that was drained via a suction tube placed near the surgical field and continuously recirculated through a closed circuit equipped with a hemodialyzer as a filter. Irrigant samples from two pigs were cultured to check for bacterial and fungal contamination. Body weight was measured before and after surgery in four pigs that had not received treatments affecting hemodynamics or causing diuresis. RESULTS: One-way flow of irrigant ensured laparoscopic vision by rinsing blood from the surgical field. Through a retroperitoneal approach, cystoprostatectomy was successfully performed in three pigs, nephrectomy in two, renal excision in two, and partial nephrectomy in one, under simultaneous ultrasonographic monitoring. Through a transperitoneal approach, liver excision and hemostasis with a bipolar sealing device were performed in three pigs, and bladder pedicle excision was performed in one pig. Bacterial and fungal contamination of the irrigant was observed on the draining side of the circuit, but the filter captured the contaminants. Body weight increased by a median of 2.1% (range, 1.2-4.4%) of initial weight after 3-5 hours of irrigation. CONCLUSIONS: Surgery under irrigation is feasible and practical when performed via a cistern through a small abdominal incision. This method is advantageous, especially in the enabling of continuous and free-angle ultrasound observation of parenchymal organs. Adverse effects of abdominal irrigation need further assessment before use in humans.

Interferon treatment for Japanese patients with favorable-risk metastatic renal cell carcinoma in the era of targeted therapy.

PURPOSE: Single-agent interferon (IFN) is no longer regarded as a standard option for first-line systemic treatment of metastatic renal cell carcinoma (RCC) in Western countries. However, some patients with favorable-risk RCC may still achieve complete and long-lasting remission in response to IFN treatment. The present study compared favorable-risk Japanese patients with metastatic RCC Japanese patients who had been treated with IFN or tyrosine kinase inhibitor (TKI) therapy as a first-line systemic therapy. MATERIALS AND METHODS: From 1995 to 2014, a total of 48 patients with favorable risk as defined by the Memorial Sloan Kettering Cancer Center criteria who did not receive adjuvant systemic therapy were retrospectively enrolled in this study. We assessed the tumor response rate, progression-free survival (PFS), and overall survival (OS). RESULTS: The objective response rate for first-line therapy was 29% in the IFN group and 47% in the TKI group, but this difference did not reach the level of statistical significance. Median OS for IFN and TKI was 71 and 47 months, respectively (p=0.014). Median first-line PFS for IFN and TKI was 20 and 16 months, respectively (no significant difference). First-line IFN therapy did not prove inferior to TKI therapy in terms of OS according to metastatic sites. CONCLUSIONS: IFN is associated with a survival benefit in Japanese patients with favorable-risk metastatic RCC in the era of targeted therapy. Further prospective study is needed.

Mechanisms of metastasis suppression by introduction of human chromosome 10 into rat prostate cancer.

AIM: The metastatic ability of a Dunning R-3327 rat prostate cancer subline (AT6.3) was suppressed by the introduction of human chromosome 10, when these hybrid cancer cells were injected subcutaneously into nude mice (Nihei et al., Genes Chromosomes Cancer 14:112-119, 1995). The present study was undertaken to clarify which step of metastasis was suppressed in the human chromosome 10-containing microcell hybrids (AT 6.3-10 clones). METHODS: Gelatin zymography, an in vitro invasion assay using a Boyden chamber and an intravenous metastasis assay involving the injection of hybrid cells into nude mice were performed. RESULTS: Gelatin zymography revealed that AT6.3-10 microcell hybrid clones expressed the 72 kD type IV collagenase (MMP-2) at an almost equal level as control microcell hybrid clones. Both the invasiveness as measured by the invasion assay and the number of lung metastases as measured by the intravenous metastasis assay of AT6.3-10 hybrid clones were significantly less than those of the AT6.3 parental clone. CONCLUSION: The human chromosome 10 suppresses both the local invasion and the metastatic process after entry into the blood circulation of rat prostate cancer. This decrease in local-invasive ability does not seem to require a decrease in MMP-2 activity.