Purpose: Analysis of circulating tumor DNA (ctDNA) in blood could allow noninvasive genetic analysis of primary tumors. Although there have been unmet needs for noninvasive methods in patients with primary central nervous system lymphoma (PCNSL), it is still not determined whether plasma ctDNA analysis could be useful for patients with PCNSL. Materials and Methods: Targeted deep sequencing of 54 genes was performed in cell-free DNA isolated from plasma samples collected pretreatment, during treatment, and at the end of treatment in 42 consecutively diagnosed PCNSL patients between January 2017 and December 2018. Results: Targeted sequencing of plasma cell-free DNA detected somatic mutations representing ctDNA in 11 cases (11/41, 27%). The detection of ctDNA was not related to the concentration of cell-free DNA or tumor volume. The mutation profiles of these 11 cases varied between patients. The most frequently mutated gene was PIM1 (4/11, 36.4%), whereas KMT2D, PIK3CA, and MYD88 were each observed in three patients (3/11, 27%). The mutations of 13 genes were concordantly found in primary tumor tissue and plasma ctDNA, giving a detection sensitivity of 45%. During the serial tracking of seven patients with complete response, the disappearance of ctDNA mutations was found in four patients, whereas three patients had detected ctDNA mutation at the end of treatment. Conclusion The plasma ctDNA mutation analysis still has limited value for surveillance and predicting treatment outcomes of PCNSL because the detection efficiency was lower than other systemic lymphomas. Thus, analytical platforms should be improved to overcome anatomical hurdles associated with PCNSL.

PURPOSE: We evaluated the efficacy of parenchymal compression in open partial nephrectomies (OPNs) compared with that of the conventional vascular clamping method. MATERIALS AND METHODS: OPNs were conducted by means of the parenchymal compression technique at our institution from April 2006. Among these, the operative outcomes of 20 consecutive patients with normal preoperative renal function (Group 1) were matched with those of 20 control patients from the database of previous operations who underwent OPN with a conventional vascular clamping method (Group 2). RESULTS: All preoperative characteristics were similar in both groups. The operative time was significantly higher for Group 2 (132.4+/-17.7 vs. 151.4+/-21.4 minutes, p=0.031). Estimated blood loss was slightly higher for Group 2, with marginal statistical significance (173.7+/-11.5 vs. 211.2+/-43.8 ml, p=0.06). Histologic examination revealed that over 80% of the tumors in both groups were renal cell carcinomas. For all patients, the pathology results of specimens were negative. Serum creatinine, checked at 1, 3, and 7 days after the operation, was significantly increased in both groups to a similar degree. However, 30 days after surgery, the patterns of serial serum creatinine levels demonstrated statistically significant differences by repeated-measures ANOVA (p<0.001), with a trend of more elevated in Group 2 than in Group 1, although values were within the normal range. No major complications occurred in either group. CONCLUSIONS: OPN using the parenchymal compression method had acceptable outcomes in terms of complete tumor control, avoiding warm ischemic time, and minimizing blooding, with good preservation of renal function and minimal complications.
Carcinoma, Renal Cell ; Constriction ; Creatinine ; Humans ; Kidney Neoplasms ; Nephrectomy ; Operative Time ; Organ Preservation ; Reference Values ; Warm Ischemia

To estimate the short-term results of robot-assisted laparoscopic radical prostatectomy (RALRP) during the learning curve, in terms of surgical, oncological and functional outcomes, we conducted a prospective survey on RALRP. From July 2007, a single surgeon performed 63 robotic prostatectomies using the same operative technique. Perioperative data, including pathological and early functional results of the patient, were collected prospectively and analyzed. Along with the accumulation of the cases, the total operative time, setup time, console time and blood loss were significantly decreased. No major complication was present in any patient. Transfusion was needed in six patients; all of them were within the initial 15 cases. The positive surgical margin rate was 9.8% (5/51) in pT2 disease. The most frequent location of positive margin in this stage was the lateral aspect (60%), but in pT3 disease multiple margins were the most frequent (41.7%). Overall, 53 (84.1%) patients had totally continent status and the median time to continence was 6.56 weeks. Among 17 patients who maintained preoperative sexual activity (Sexual Health Inventory for Men > or = 17), stage below pT2, followed up for > 6 months with minimally one side of neurovascular bundle preservation procedure, 12 (70.6%) were capable of intercourse postoperatively, and the mean time for sexual intercourse after operation was 5.7 months. In this series, robotic prostatectomy was a feasible and reproducible technique, with a short learning curve and low perioperative complication rate. Even during the initial phase of the learning curve, satisfactory results were obtained with regard to functional and oncological outcome.
Aged ; Humans ; Laparoscopy ; methods ; Male ; Middle Aged ; Outcome Assessment (Health Care) ; Postoperative Complications ; etiology ; Prospective Studies ; Prostatectomy ; adverse effects ; education ; methods ; Prostatic Neoplasms ; pathology ; surgery ; Robotics ; Sexual Behavior ; Time Factors ; Treatment Outcome ; Urinary Incontinence

PURPOSE: To investigate synergistic effect of local cryoablation with systemic immunotherapy, the tumor control ability and immunologic responses of combining these two modalities was compared with that of cryoablation, surgical excision, and immunotherapy only group in a tumor re-challenge model. MATERIALS AND METHODS: Preliminary experiments were performed in two stages. The first stage consisted of 36 Balb/c mice with Renca bearing tumors imbedded in the right thigh, and was treated with interleukin-2 (IL-2) and interferon-alpha(IFN-alpha) to evaluate the efficacy of immunotherapy and to determine the adequate dosage. The second stage was performed on 10 mice, to evaluate histological changes and efficacy after cryoablation. The main experiment was performed on 48 mice, divided into 6 groups of control with tumor implantation, excision of tumor, excision combined with immunotherapy, cryoablation of tumor, cryoablation with immunotherapy and control without tumor. After treatment, tumor re-challenge was performed with Renca cell, then the growth pattern was evaluated with physical measurements, and immune response was investigated with fluorescent activated cell sorter and cytotoxicity assay. RESULTS: Preliminary studies on immunologic efficacy revealed that IL-2 and IFN-alpha have a dose dependent inhibition of tumor growth. The main experiment evaluating the efficacy of combination treatment revealed that cryoablation with immunotherapy proved to be most effective in terms of tumor recurrence and tumor growth inhibition, yet the difference was not statistically significant from monotherapy with cryoablation. However, cytotoxicity was significantly increased cryoablation with immunotherapy compared with other groups. CONCLUSIONS: Cryoablation on tumor re-challenge mice model showed advantages with immunotherapy most prominently in cytotoxicity.
Mice ; Animals

PURPOSE: To evaluate the feasibility and efficacy of performing laparoscopic renal cryoablation (LRC) for the treatment of RCC, as compared with open partial nephrectomy (OPN), which is the established NSS. MATERIALS AND METHODS: From April 2004, among the patients who underwent LRC with a 1.47 mm cryoprobe, we enrolled 20 patients who were pathologically confirmed as having RCC with a tumor size smaller than 4 cm. These patients were matched with a group of 20 patients, who were selected based on the pre-operative characteristics of the tumor and those of the patients, from a pre-existing database of the patients who underwent OPN during the same period. RESULTS: The mean age and tumor size were 56.3+/-11.5 years and 2.4+/-1.7 cm in the LRC group, and 57.6+/-10.9 years and 2.2+/-1.1 cm in the OPN group. The two groups were similar for their age, gender, BMI, ASA, the tumor characteristics and the indications for operation. While the pathologic results and the operation time showed similarity, the EBL (98+/-87 ml vs 351+/-147 ml, respectively, p=0.001), the transfusion rate (10% vs 40%, respectively, p=0.03) and the hospital stay (4.2+/-1.5 days vs 8.2+/-2.4 days, respectively, p=0.005) were significantly less in the LRC group. Major complications did not occur in the LRC group, but in the OPN group, one patient experienced urine leakage and one patient had a perirenal hematoma. During the mean follow up of 27.3+/-10.8 months and 28.7+/-14.9 months for each group, respectively, all the patients remained disease- free with no evidence of local recurrence or metastases. CONCLUSIONS: LRC using ultra-thin cryoprobes for the treatment of small RCC showed similar effective oncologic results with the merits of minimal invasiveness, as compared with OPN, during the intermediate term follow up.
Carcinoma, Renal Cell ; Cryosurgery ; Follow-Up Studies ; Hematoma ; Humans ; Length of Stay ; Nephrectomy ; Recurrence

Nocardiosis is well-known opportunistic infection in immunocompromised patients. The timely diagnosis and treatment, however, is still a difficult problem. Recently, as newer molecular techniques, particularly 16S rRNA sequencing, are implemented, the diagnosis and management of the infection are improving. We report a case of lung abscess in a 39-year-old-man who underwent kidney transplantation. He was diagnosed of Nocardia elegans by 16S rRNA sequencing and was cured of the infection with appropriate antibiotic therapy.
Immunocompromised Host ; Kidney ; Kidney Transplantation ; Lung ; Lung Abscess ; Nocardia ; Nocardia Infections ; Opportunistic Infections

Nocardiosis is well-known opportunistic infection in immunocompromised patients. The timely diagnosis and treatment, however, is still a difficult problem. Recently, as newer molecular techniques, particularly 16S rRNA sequencing, are implemented, the diagnosis and management of the infection are improving. We report a case of lung abscess in a 39-year-old-man who underwent kidney transplantation. He was diagnosed of Nocardia elegans by 16S rRNA sequencing and was cured of the infection with appropriate antibiotic therapy.
Immunocompromised Host ; Kidney ; Kidney Transplantation ; Lung ; Lung Abscess ; Nocardia ; Nocardia Infections ; Opportunistic Infections

The objectives of this study were to explore whether ovarian vascular endothelial growth factor (VEGF) expression in mice can be regulated by IL-6 (interleukin-6), angiotensin II, FSH, and hCG; and to test whether the mouse ovarian VEGF expression can result in angiogenesis. The ICR mice were sacrificed, and their ovaries were recovered. Recovered ovaries were treated with IL-6, angiotensin II, FSH, and hCG separately and incubated for 24 hours in alpha-MEM. Expression of mRNA and protein of VEGF were assessed by RT-PCR and immunohistochemistry. The resulting angiogenesis was evaluated through immunohistochemical analysis for CD34. Treatment of mice ovaries with IL-6, FSH, and hCG resulted in a significant increase of VEGF mRNA, and IL-6 was the most potent inducer of VEGF. IL-6 and FSH resulted in increased neovascularization in the follicular phase of mouse ovaries. In contrast, angiotensin II could not increase VEGF expression or neovascularization. We documented an in vitro increase in VEGF expression by IL-6, FSH, and hCG; and reaffirmed that the proliferative response of murine ovarian endothelial cells paralleled an increase of VEGF expression.
Vascular Endothelial Growth Factor A/analysis/*genetics ; RNA, Messenger/analysis ; Ovary/*metabolism ; Mice, Inbred ICR ; Mice ; Interleukin-6/pharmacology ; Immunohistochemistry ; Gene Expression Regulation/*drug effects ; Follicle Stimulating Hormone/pharmacology ; Female ; Chorionic Gonadotropin/pharmacology ; Antigens, CD34/analysis ; Animals

OBJECTIVE: The purpose of the current series of experiments were to assess the effect of GM-CSF, as a medium supplement, on the development of mouse embryos and the expression of LIF and IL-1beta mRNA. MATERIALS AND METHODS: Mouse 2-cell embryos were collected from the oviducts of 6 weeks old ICR mice at 48 hours after hCG injection. Embryos were cultured in P-1 medium supplemented with mouse GM-CSF(0,1,5,10 ng/ml). The embryo development to blastocysts and hatching blastocysts was assessed and the cell number in blastocyst was also examined. Using RT-PCR, the expressions of LIF and IL-1beta mRNA in blastocyst were evaluated in the GM-CSF supplemented group and control group. RESULTS: In mouse, the addition of GM-CSF increased the percentage of blastocysts(65.5%, 68.6%, 73.0% and 76.1% for control and 1, 5 and 10 ng/ml, respectively), and increased the proportion of hatching blastocysts(35.2%, 36.4%, 43.2% and 53.0% for control and 1, 5 and 10 ng/ml, respectively). The mean cell numbers in blastocyst were significantly increased in GM-CSF supplemented groups compared to control group. LIF and IL-1beta expression in blastocysts were significantly higher in GM-CSF supplemented group than in control group. CONCLUSION: The results of experiment by mouse embryos showed beneficial effects of GM-CSF as a medium supplement. Furthermore, the addition of GM-CSF significantly increased the expression of LIF and IL-1beta in mouse embryos. These results suggest that GM-CSF might be a important molecule in embryo implantation.
Animals ; Blastocyst ; Cell Count ; Embryo Implantation ; Embryonic Development* ; Embryonic Structures* ; Female ; Granulocyte-Macrophage Colony-Stimulating Factor* ; Mice* ; Mice, Inbred ICR ; Oviducts ; Pregnancy ; RNA, Messenger

Angiosarcoma is very rare but highly malignant soft tissue tumor derived from the vascular endothelium. This tumor is most commonly found in the skin and subcutaneous tissues. Angiosarcoma is known to cause early and widespread metastasis leading to a very poor prognosis of less than 24 months. We report a case of angiosarcoma developed in the temporoparietal scalp of a 84-year-old man. The patient was referred for us consultation after failed systemic antibiotic treatment, incision drainage treatment for "cellulitis" by the general physician. We performed excision and biopsy. The histologic finding of the lesion showed that irregular, complex vascular channels in dermis. The tumor cells were positive for Factor VIII-related antigen. The lesion was confirmed as cutaneous angiosarcoma. We recommended a radical surgery and reconstruction followed by adjuvant radiation, but the patient refused. The patient was expired 2 months thereafter because of a massive hemorrhagic pleural effusion by suspicious distant metastasis. Authors reported important aspects of clinical findings, histologic features and therapeutic options of the scalp angiosarcoma.
Aged, 80 and over ; Biopsy ; Dermis ; Drainage ; Endothelium, Vascular ; Hemangiosarcoma* ; Humans ; Neoplasm Metastasis ; Pleural Effusion ; Prognosis ; Scalp* ; Skin ; Subcutaneous Tissue ; von Willebrand Factor