Skin graft with dermis and appendages generated in vivo by cell competition.

Autologous skin grafting is a standard treatment for skin defects such as burns. No artificial skin substitutes are functionally equivalent to autologous skin grafts. The cultured epidermis lacks the dermis and does not engraft deep wounds. Although reconstituted skin, which consists of cultured epidermal cells on a synthetic dermal substitute, can engraft deep wounds, it requires the wound bed to be well-vascularized and lacks skin appendages. In this study, we successfully generate complete skin grafts with pluripotent stem cell-derived epidermis with appendages on p63 knockout embryos' dermis. Donor pluripotent stem cell-derived keratinocytes encroach the embryos' dermis by eliminating p63 knockout keratinocytes based on cell-extracellular matrix adhesion mediated cell competition. Although the chimeric skin contains allogenic dermis, it is engraftable as long as autologous grafts. Furthermore, we could generate semi-humanized skin segments by human keratinocytes injection into the amnionic cavity of p63 knockout mice embryos. Niche encroachment opens the possibility of human skin graft production in livestock animals.

Functional calcium-responsive parathyroid glands generated using single-step blastocyst complementation.

Patients with permanent hypoparathyroidism require lifelong replacement therapy to avoid life-threatening complications, The benefits of conventional treatment are limited, however. Transplanting a functional parathyroid gland (PTG) would yield better results. Parathyroid gland cells generated from pluripotent stem cells in vitro to date cannot mimic the physiological responses to extracellular calcium that are essential for calcium homeostasis. We thus hypothesized that blastocyst complementation (BC) could be a better strategy for generating functional PTG cells and compensating loss of parathyroid function. We here describe generation of fully functional PTGs from mouse embryonic stem cells (mESCs) with single-step BC. Using CRISPR-Cas9 knockout of Glial cells missing2 (Gcm2), we efficiently produced aparathyroid embryos for BC. In these embryos, mESCs differentiated into endocrinologically mature PTGs that rescued Gcm2-/- mice from neonatal death. The mESC-derived PTGs responded to extracellular calcium, restoring calcium homeostasis on transplantation into mice surgically rendered hypoparathyroid. We also successfully generated functional interspecies PTGs in Gcm2-/- rat neonates, an accomplishment with potential for future human PTG therapy using xenogeneic animal BC. Our results demonstrate that BC can produce functional endocrine organs and constitute a concept in treatment of hypoparathyroidism.

Three-dimensional scanner with a modified evaluation method for measuring hand edema subtitle: an idea for accurate evaluation and preliminary fundamental and clinical validation.

Acute hand edema often results in loss of fine hand motor activities, especially without appropriate care. There is still no reliable and easy to use method to measure hand edema. In this study, we tested a handheld three-dimensional (3D) scanner on plastic male and female hand models using a whole hand measuring method (WM) and a modified method (MM) which excluded fingers. We evaluated the intra-rater reliability and inter-rater reliability and compared the measured volumes to computed tomography (CT) findings. Statistical analysis showed that the 3D scan method was valid and reliable for both WM and MM methods. In WM, intra-rater and inter-rater reliability were 0.97 and 0.84, with 95% confidence interval (CI) of 0.87-1.00 and 0.61-0.94, respectively. In MM, intra-rater and inter-rater reliability were 0.96 and 0.83, with 95% CI of 0.84-1.00 and 0.61-0.94, respectively. In comparison to the CT, the differences between 3D scan and CT in the male model volumes were 30.35 ± 2.70 cm3 (mean ± standard deviation) for WM and 11.60 ± 2.07 cm3 for MM. In the female model, the differences were 18.92 ± 2.66 cm3 and 11.18 ± 2.35 cm3, respectively. In both models, MM was significantly more accurate than WM (p < 0.001). When used in a clinical case, the scanner recorded changes in actual volume through the course of treatment. This cost-effective handheld 3D camera can be a reliable tool for evaluating hand edema even in cases of acute injury.

The Membrane-Like Structure From Extensor Tendon to the Nail in the Distal End of Digits: An Anatomical Study of Structure, Function, and Utility.

METHODS: The nail structures of 6 cadavers were investigated in each of the 10 digits of the hand. In the histological study, the thickness, length, and location of the SEP were measured in each digit of 3 cadavers. In the other 3 cadavers, the moving distance of the SEP was measured macroscopically with the distal interphalangeal joint in flexion at 0 to 60 degrees for confirmation of the function. This moving distance could be considered as an indicator of the SEP straining the surrounding (retaining) structure and improving the stability of the nail in pinches. RESULT: The SEP was recognized in all the digits. The average length of the SEPs was 2.38 ± 0.11 mm (mean ± SE). The average thickness of the SEPs was 0.35 ± 0.02 mm. The nail matrix and its feeding artery were found beneath the SEP in all digits. The average moving distance of the SEP was 1.38 ± 0.06 mm. This moving distance could be considered sufficiently large to support the role of SEP in the pinches compared with the excursion of the extensor tendon at the DIP joint in a previous report. CONCLUSIONS: The SEP has been shown to play an essential role in fingertip stabilization in pinches. It can serve as an anatomical marker to avoid iatrogenic damage to the nail matrix in surgical approaches.

Angiogenic efficacy of ASC spheroids filtrated on porous nanosheets for the treatment of a diabetic skin ulcer.

Stem cell transplantation is expected to be an effective treatment for intractable skin ulcers by promoting angiogenesis; however, it is challenging to quickly realize a sufficient bloodstream for the ulcers. For this treatment, sheet-like materials with monolayer cells such as cell sheets have been investigated. However, they have a limitation of cell number that can be transplanted at one time due to the two-dimensional, monolayer cell structure, and sufficient secretion of growth factors cannot be expected. In this regard, cellular aggregates, such as spheroids, can reproduce three-dimensional cell-cell interactions that cause biological functions of living tissues more representative than monolayer cells, which is important to achieving efficient secretion of growth factors. In this study, we focused on free-standing porous polymer ultrathin films ("porous nanosheets") comprising poly(d,l-lactic acid) (PDLLA) and succeeded in developing a spheroid-covered nanosheet, on which more than 1000 spheroids from adipose-tissue derived stem cells (ASCs) were loaded. The porous structure with an average pore diameter of 4 µm allowed for facile filtration and carrying spheroids on the nanosheet, as well as sufficient oxygen and nutrients inflow to the cells. The spheroid-covered nanosheet achieved homogeneous transference of spheroids to a whole skin defect in diabetic model mice. Given the continuous release of vascular endothelial growth factor (VEGF) from the spheroids, the transplanted spheroids promoted healing with more accelerated angiogenesis than a nanosheet with a monolayer of cells. The spheroid-covered nanosheet may be a new regenerative material for promoting intractable skin ulcer healing.

Enhanced cellular engraftment of adipose-derived mesenchymal stem cell spheroids by using nanosheets as scaffolds.

The short survival time of transplanted adipose-derived mesenchymal stem cells (ASCs) is a problem for skin wound healing. Transplantation after the formation of cellular spheroids has been investigated as a promising method for prolonging cellular survival. However, there have been technical restrictions for transplantation of spheroids in clinical practice. Here, we show an effective method for transplantation of ASC spheroids onto skin wounds in order to efficiently cure refractory ulcers. To assist anchoring of spheroids onto skin wounds, we used a 120-nm-thick free-standing film (nanosheet) that has a highly adhesive property. Bioluminescence imaging showed that ASC spheroids carried by the nanosheet survived for 14 days, which is about two-times longer than that previously reported. Wounds treated with a nanosheet carrying ASC spheroids were 4-times smaller than untreated wounds on day 14. This method for transplantation of spheroids could be applied to cell therapy for various refractory skin wounds.

Multi-institutional retrospective analysis of ultrahypofractionated radiotherapy for Japanese prostate cancer patients.

To report outcomes and risk factors of ultrahypofractionated (UHF) radiotherapy for Japanese prostate cancer patients. This multi-institutional retrospective analysis comprised 259 patients with localized prostate cancer from 6 hospitals. A total dose of 35-36 Gy in 4-5 fractions was prescribed for sequential or alternate-day administration. Biochemical failure was defined according to the Phoenix ASTRO consensus. Toxicities were assessed using National Cancer Institute Common Toxicity Criteria version 4. Tumor control and toxicity rates were analyzed by competing risk frames. Median follow-up duration was 32 months (range 22-97 months). 2- and 3-year biochemical control rates were 97.7% and 96.4%, respectively. Initial prostate-specific antigen (p < 0.01) and neoadjuvant androgen deprivation therapy (p < 0.05) were identified as risk factors for biochemical recurrence. 2- and 3-year cumulative ≥ Grade 2 late genitourinary (GU) toxicities were 5.8% and 7.4%, respectively. Corresponding rates of gastrointestinal (GI) toxicities were 3.9% and 4.5%, respectively. Grade 3 rates were lower than 1% for both GU and GI toxicities. No grade 4 or higher toxicities were encountered. Biologically effective dose was identified as a risk factor for ≥ Grade 2 late GU and GI toxicities (p < 0.05). UHF radiotherapy offered effective, safe treatment for Japanese prostate cancer with short-term follow-up. Our result suggest higher prescribed doses are related to higher toxicity rates.

Triangular extension of hinge flaps: A novel technique to resolve stomal stenosis and prevent restenosis in staged buccal mucosal urethroplasty.

OBJECTIVES: To verify the utility of triangular extension of a hinge flap in buccal mucosal staged urethroplasty to resolve stomal stenosis after the first stage and ultimately prevent restenosis. METHODS: A total of 23 patients (triangular extension group) were studied in 2013-2019. In the first stage, buccal mucosa was transplanted, and an extended triangle portion of the mucosa was placed beside the proximal and/or distal stoma that was created when the stricture segment of the urethra was resected. In the second stage, during tubularization of the urethral plate, an incision was made at the stoma to increase the caliber to which the triangular extension was inserted. The procedure was considered successful when a 17-Fr flexible cystoscope passed through the reconstructed urethra at 6 months after the second-stage urethroplasty and no additional surgery or bougie dilation required. The clinical course of the triangular extension group was compared with 24 patients who underwent conventional staged urethroplasty (control group). RESULTS: In total, 20 patients from each group underwent second-stage surgery. No patients in the triangular extension group required additional revision surgery because of stomal stenosis after first-stage surgery, whereas five (20%) control patients did. Urethroplasty was successful in 19 patients (95%) in the triangular extension group and in 19 patients (95%) in the control group. Uroflowmetry after the second-stage surgery indicated that the mean maximum urinary flow rate was 21.5 and 15.8 mL/s after triangular extension and the control procedure, respectively (P = 0.027). CONCLUSIONS: The triangular extension technique reduces the need for revision surgery and prevents postoperative restenosis.

Aesthetic Consideration in a Patient With Lipomatosis.

ABSTRACT: This is the first report of multiple parosteal lipomas as a late complication of aesthetic procedures. A 70-year-old woman presented with multiple frontal nodules that had grown slowly over 5 years. She underwent forehead-lifting surgery 30 years ago and botulinum toxin injection 3 years ago. Computed tomography showed six low-density nodules measuring 10 to 20 mm just above the frontal bone. The tumors were resected via a parietal coronal incision. Histopathological findings revealed parosteal lipoma with foreign bodies. At 1 year postoperatively, there has been no recurrence or complications. The multiple lesions corresponded to the sites of the aesthetic procedures. The mesenchymal cells in the periosteum seemed to be stimulated by cytokines released from a postoperative hematoma or damaged periosteum, resulting in tumorigenesis. When performing aesthetic procedures in the face, care should be taken to avoid unnecessary injury to the periosteum, given the possibility of tumor development.Level of evidence: Level V, case report.

Management of Infected Calcific Myonecrosis: A Report of 2 Cases.

Calcific myonecrosis (CM) is a rare condition in which a large calcified mass develops after trauma. Generally, CM occurs in a lower extremity, and there have been no reports of its occurrence in the upper arm. We report 2 cases of infected CM, including a rare case of CM occurrence in the arm and a typical case in the leg. Case 1: An 84-year-old woman presented with a draining sinus and a large calcified mass in the arm and axillary region. The mass involved the neurovascular bundle; thus, complete resection was impossible. We performed surgical debridement and postoperative negative-pressure wound therapy with instillation and dwell. Case 2: A 43-year-old man presented with a large calcified mass in the right leg and 2 draining sinuses. After surgical debridement, negative-pressure wound therapy was initiated. However, the wound became infected, and we performed additional debridement, followed by a split thickness skin grafting. The infection was controlled in both patients, although complete resection was not feasible. Complete resection is generally considered the optimum treatment for infected CM, but it is difficult to achieve in some patients. Negative-pressure wound therapy with instillation and dwell appears as a good option for postoperative management if complete resection of infected CM cannot be achieved.

Stepwise surgery with variable adjustments for severe blepharochalasis with multiple chemical sensitivity: a case report.

We report a 29-year-old man with blepharochalasis and multiple chemical sensitivity (MCS). Although standard blepharoplasty with aponeurotic fixation was performed, palpebral ptosis recurred after 3 months. Eyelid function and appearance improved after additional operations. A stepwise surgical approach is appropriate in patients with blepharochalasis and MCS.

A case of nodular fasciitis that was difficult to distinguish from sarcoma.

INTRODUCTION: Nodular fasciitis is a reactive proliferative lesion. It is often difficult to distinguish from sarcoma, such as malignant peripheral nerve sheath tumor (MPNST). Therefore, both pathological findings and clinical features must be considered. PRESENTATION OF CASE: A 75-year-old man presented with a 1 × 1 cm mass on his left forearm that had enlarged rapidly without specific symptoms. Magnetic resonance imaging revealed a mass adjacent to brachioradialis. The lesion showed iso-intensity to muscle on T1-weighted images and hyperintensity on T2-weighted images. We made a clinical diagnosis of nodular fasciitis. Under observation, the mass gradually decreased in size and disappeared after two months. Four years later, another lesion appeared at the same site. We performed total excisional biopsy and histopathological examination indicated low grade MPNST or recurrent nodular fasciitis. Since malignancy could not be excluded, wide resection was performed. At 4 years postoperatively, there has been no recurrence. DISCUSSION: In this patient, nodular fasciitis of the right forearm was diagnosed clinically and showed spontaneous regression. However, recurrence was noted after four years. While the clinical features suggested recurrent nodular fasciitis, pathological findings indicated the possibility of low grade MPNST. CONCLUSION: When it is difficult to determine whether a lesion such as nodular fasciitis is benign or malignant, the patient should be managed by considering the possibility of malignancy.

Appropriate Use of Intravenous Unfractionated Heparin after Digital Replantation: A Randomized Controlled Trial Involving Three Groups.

BACKGROUND: The purpose of this study was to clarify the appropriate use of unfractionated heparin as an anticoagulation agent after digital replantation. METHODS: This study was a prospective, randomized, single-blind, blinded-endpoint method, three-arm, parallel-group, controlled clinical trial conducted at a single institution. A total of 88 patients (101 fingers) following digital amputation and subsequent repair by anastomosis of both arteries and veins were randomly allocated into three groups: (1) control group (no heparin dose), (2) low-dose heparin group (10,000 IU/day), and (3) high-dose heparin group (start at 15,000 IU/day, then adjust the dose to achieve an activated partial thromboplastin time of 1.5 to 2.5 times the baseline). The outcomes were assessed regarding the proportion of success at 2 weeks after replantation of amputated digits, total or partial necrosis, and occurrence of complications. RESULTS: No significant differences were found among the three groups, except for complications of congestion. The odds ratio of the heparin group compared with the control group for a success proportion was 5.40 (95 percent CI, 0.85 to 34.20; p = 0.027) in subjects aged 50 years or older. Significant elevations of activated partial thromboplastin time, aspartate transaminase, and alanine aminotransferase occurred in high-dose heparin groups on day 7. CONCLUSION: Unfractionated heparin administration is considered effective for patients aged 50 years or older, although the routine use of unfractionated heparin is not necessary after digital replantation. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

Hinge Flap with Triangular Extension for Reconstruction of Pharyngocutaneous and Laryngocutaneous Fistulas.

Hinge flaps are commonly used for closure of a pharyngocutaneous fistula (PCF) or laryngocutaneous fistula. These flaps are employed to augment the wall of the pharynx or larynx, but the junction between the reconstructed and native lumens can eventually become narrow and irregular after reconstruction with standard hinge flaps. We devised a method of adding a triangular extension to the end of either or both flaps and used it to treat 3 patients. In 1 patient who developed a PCF (4 × 10 cm) after laryngectomy followed by radiotherapy, the fistula was closed with 2 hinge flaps. One flap had a caudal triangular extension. The residual skin defect was covered by a pedicled latissimus dorsi musculocutaneous flap. Another patient who developed a PCF (2.5 × 3 cm) after laryngectomy underwent 2-stage reconstruction using a buccal mucosal graft with a triangular extension, followed by 2 hinge flaps. A patient who developed an laryngocutaneous fistula (1 × 2 cm) after radiotherapy and subsequent partial laryngectomy underwent reconstruction using 2 hinge flaps, each of which had a triangular extension. The skin defect was covered by another flap. Postoperative CT or video fluoroscopic examination of swallowing showed a smooth lumen with no strictures in all 3 patients. The triangular extension of the hinge flap supplements the pharyngeal/laryngeal wall at the junction between the reconstructed and intact regions, thus avoiding postoperative stricture. Especially with PCF reconstruction, restoration of a smooth luminal surface minimizes dysphagia.

[Influence of position of ionization chamber and leaf-end on verification value in IMRT verification for prostate cancer].

In IMRT for prostate cancer, MU verification is performed by the actual measurement. We have experienced a remarkable improvement in results, once succeeding in finding out the more suitable and optimal evaluation dose point in some cases even though the deviation between a designed MU score and our actual record gained at the iso-center was more than 3%. In this study, we tried to demonstrate how much influence would be given to the point dose verification by the 3D arrangement between an ion chamber and tips of the MLC. The five cases in which the bias between each actual datum and planed MU score showed that about 3% were picked up and through these MLC configurations, 8 leaf-ends around the chamber were highlighted as the influential ones. After each distance from 4 pairs, a total of 8 leaves to the axis (the mid-line) of our ion chamber were mapped. The indexes (PlanLeafScores) were computed through these distances and segmental MU scores. The ratio of these scores and results obtained at the 12 sites within 1 cm from the iso-center were carried out by single regression analysis. In all cases the ratios of planed MU values to the actual ones tended to go down in inverse proportion to the increase in PlanLeafScores (r<-0.77, p<0.002). As the dimensional arrangement between the ion chamber and the edges of the MLC were thought to determine the result of the verification. PlanLeafScores will enable us to determine the optimal evaluation of the dose point.

Dose selection for optimal treatment results and avoidance of complications.

What is the optimal treatment for metastatic brain tumors (MBTs)? We present our experience with gamma knife (GK) treatments for patients with five or more MBTs. Our new formula for predicting patient survival time (ST), which was derived by combining tumor control probability (TCP) calculated by Colombo's formula and normal tissue complication probability (NTCP) estimated by Flickinger's integrated logistic formula, was also evaluated. ST=a*[(C-NTCP)*TCP]+b; a, b, C: const. Forty-one patients (23 male, 18 female) with more than five MBTs were treated between March 1992 and February 2000. The tumors originated in the lung in 15 cases, in the breast in 8. Four patients had previously undergone whole brain irradiation (WBI). Ten patients were given concomitant WBI. Thirteen patients had additional extracranial metastatic lesions. TCP and NTCP were calculated using Excel add-in software. Cox's proportional hazards model was used to evaluate correlations between certain variables and ST. The independent variables evaluated were patient factors (age in years and performance status), tumor factors (total volume and number of tumors in each patient), treatment factors (TCP, NTCP and marginal dose) and the values of (C-NTCP)*TCP. Total tumor number was 403 (median 7, range 5-56). The median total tumor volume was 9.8 cm3 (range 0.8-111.8 cm3). The marginal dose ranged from 8 to 22 Gy (median 16.0Gy), TCP from 0.0% to 83% (median 15%) and NTCP from 0.0% to 31% (median 6.0%). (0.39-NTCP)*TCP ranged from 0.0 to 0.21 (median 0.055). Follow-up was 0.2 to 26.2 months, with a median of 5.4 months. Multiple-sample tests revealed no differences in STs among patients with MBTs of different origins (p=0.50). The 50% STs of patients with MBTs originating from the breast, lung and other sites were 5.9, 7.8 and 3.5 months, respectively. Only TCP and (0.39-NTCP)*TCP were statistically significant covariates (p=0.014, 0.001, respectively), and the latter was a more important predictor of ST than the former (Beta= -2.2, -14.1, respectively). The relationship between (0.39-NTCP)*TCP and ST was significant. Linear regression analysis showed this value to predict ST (p=0.002, R2=0.22). The slope of the regression line for patients with MBTs originating from the breast was steeper (a=218.2, p=0.08, R2=0.41) than the slopes of regression lines for patients with tumors of other origins (lung; a=56.8, p=0.004, R2=0.49, others; a=50.4, p=0.03, R2=0.25). In treating multiple lesions, the maximum doses and dose distribution for individual lesions were often different. The formula described by Colombo is used to calculate the residual clonogenic cell number of every sub-volume of the tumor, with different doses. NTCP must also integrate every complication probability for each sub-volume of normal brain tissue in the relatively high dose area in proximity to the tumor. Herein, we present a method for determining the irradiation dose necessary for cases with multiple brain metastases. A personal computer-aided calculation is employed.

[Development of a respiratory monitoring device for truncal stereotactic radiotherapy using an abdominal pressure-detecting system with Stereotactic Body Frame].

The Stereotactic Body Frame, which was devised as a fastening unit for the irradiation of various truncal lesions, has obtained a good reputation for its high-precision reproductivity. This device is accessorized with 'Diaphragm Control', which can reduce the respiratory movement of intra-thoracic organs. In this study, to investigate the possibility of a respiratory monitor using our device, we try to clarify the relationship between the pressure against the abdominal board of 'Diaphragm Control' and each constrained tidal respiratory movement. Our original software was programmed to detect and analyze these data with our personal computer from some ready-made highly sensitive pressure detectors. In any fundamental performance of this system, response time is less than 1 msec at 115,200 bps, minimum detectable weight is 420 g, linearity correlation between loading weight and pressure index value is seen from 1000 g to 6000 g loading, and reproducibility of measurement is evaluated by coefficient of variation (CV=0.95% at 3000 g loading). It has sufficient capability to be used as a respiratory monitoring device during radiation therapy. In an experiment with three volunteers, the results revealed a positive correlation between pressure index value and ventilation air volume by spirometer. The decision coefficients (R(2)) were 0.7717, 0.7995, and, 0.8684, respectively. Our original respiratory monitoring device can be used for quantitative respiratory suppression and unexpected breathing detection without loading additional stress on the patient.

[Technical considerations on the usage of a general-purpose flatbed image scanner when making a dose-density table].

The DD-System is a dose-distribution system for analyzing the film method with a general-purpose flatbed image scanner. By analyzing the analogue digital conversion(ADC)value of each pixel acquired by the DD-system, we examined the technical problems of measurement with the scanner when making a dose-density table. When film of uniform density was measured, the ADC values distributed normally. Deviation of the values at the same pixel point on another time was about one-ten thousandth of the average. Deviation of the values from the time the scanner was turned on was in the same range. Although it may be negligible, the values measured at a peripheral area on the flatbed deviated about 2SD from the average measured at the central area. Further, deviation of the value obtained with a shade covering the outside of the irradiation field from that taken without the shade was about one thousandth. These deviations are not negligible. In the case of making a dose-density table with a DD-System and a general-purpose flatbed image scanner, the film should be set in the center of the flatbed, and the sampling area should be selected from those areas where the ADC values are distributed normally. Then proper data can be obtained and more accurate tables can be made.

Ommaya reservoir placement followed by Gamma Knife surgery for large cystic metastatic brain tumors.

OBJECT: The combination approach of Ommaya reservoir placement and Gamma Knife surgery (GKS) was evaluated for the treatment of large cystic metastatic brain tumors. METHODS: The medical records of 22 patients harboring 28 tumors, who underwent Ommaya reservoir placement followed by GKS for large cystic metastatic brain tumors were retrospectively reviewed. The patients' ages ranged 26 to 77 years (mean 57.1 years). The most common locations of primary malignancy were the breast (11 patients) followed by the lung (seven patients). The mean maximum diameter of the tumor was 40.1 mm before Ommaya reservoir placement and 31.2 mm at GKS (mean reduction of 19.9%). The mean calculated tumor volume at GKS was 13.4 cm3. The mean tumor margin dose was 16 Gy in 17 patients treated by GKS only and 11 Gy in five patients treated using both GKS and external radiotherapy. The mean follow-up period was 11.5 months. Nineteen (67.9%) of the 28 tumors were controlled. The median patient survival time was 7 months. Asymptomatic intracystic hemorrhage associated with Ommaya reservoir placement was seen in two patients with four tumors, but no serious complication occurred. CONCLUSIONS: Ommaya reservoir placement followed by GKS is relatively effective and safe for large cystic metastatic brain tumors. Gamma Knife surgery should be performed within a few days of Ommaya reservoir placement. Reaccumulation and high viscosity of cystic content must be considered.

Gamma knife surgery for metastatic brain tumors from renal cell carcinoma.

OBJECT: The authors evaluated the results of Gamma Knife surgery (GKS) for the treatment of metastatic brain tumors from renal cell carcinoma (RCC). METHODS: The authors conducted a retrospective review of the clinical characteristics and treatment outcomes in 69 patients with metastatic brain tumors from RCC who underwent GKS at the authors' institution. Fifty-one patients were men, and 18 were women. The mean patient age was 64.2 years (range 45-85 years). The 69 patients underwent a total of 104 GKS procedures for treatment of 314 tumors. Eighteen patients received repeated GKS. Follow-up magnetic resonance (MR) imaging was used at a mean of 7.1 months after GKS to evaluate the change in 132 tumors after treatment. The mean prescription dose at the tumor margin was 21.8 Gy. The tumor growth control rate was 82.6%. Tumor volume and the delivered peripheral dose were significantly correlated with tumor growth control on univariate and multivariate analyses. Sixty (45.5%) of the 132 tumors assessed with MR imaging were associated with apparent peritumoral edema at the time of GKS. After treatment, peritumoral edema disappeared in 27 tumors, decreased in 13, was unchanged in 16, and progressed in four. Newly developed peritumoral edema after GKS was rare. The delivered peripheral dose was significantly correlated with control of peritumoral edema. The overall median survival time after GKS was 9.5 months. In this study, 34 patients died of systemic disease and 10 died of progressive brain metastases. Multivariate analysis showed that the number of lesions at the first GKS, the Karnofsky Performance Scale score at the first GKS, the recursive partitioning analysis classification, and the interval from diagnosis of RCC to brain metastasis were significantly correlated with survival time. CONCLUSIONS: Gamma Knife surgery is effective for metastatic brain tumors from RCC. The disappearance rate of tumors is relatively low, but growth control is high. The delivered dose to the tumor margin is significantly correlated with the control of peritumoral edema. Gamma Knife surgery should be used as the initial treatment modality, if possible, even in patients with multiple metastases. Repeated GKS is recommended for newly developed brain metastases because of the low sensitivity of RCC to conventional radiation therapy.