Mitral Valve Regurgitation in Klippel-Feil Syndrome With Related Thoracic Deformity.

Klippel-Feil syndrome, characterized by congenital fusion of any 2 or more cervical vertebrae, is a rare disorder in which skeletal and other organ system-related abnormalities have been reported. This article reports a case of mitral valve regurgitation in a patient with Klippel-Feil syndrome and related thoracic deformity who underwent mitral valvuloplasty. Postoperatively, the mitral valve regurgitation disappeared, and there has been no recurrence for 3 years. This case highlights mitral valvuloplasty via median sternotomy as an excellent treatment for mitral valve regurgitation in a patient with thoracic deformity related to Klippel-Feil syndrome.

The Sum of the Leg Length Discrepancy and the Difference in Global Femoral Offset Is Equal to That of the Contralateral Intact Side and Improves Postoperative Outcomes after Total Hip Arthroplasty: A Three-Dimensional Analysis.

Background/Objectives: Global femoral offset (GFO) and leg length discrepancy (LLD) affect outcomes after total hip arthroplasty (THA). Moreover, the sum of the difference in GFO between the THA and non-surgical sides and LLD (SGL) reportedly affects the outcomes in a two-dimensional evaluation. We examined the association of the GFO, LLD, and SGL with the Harris Hip Score (HHS) using a three-dimensional (3D) evaluation. Methods: We retrospectively surveyed 172 patients with hemilateral hip osteoarthritis who underwent THA. The GFO, LLD, and SGL were measured using the 3D pelvis and femur models; these models were adjusted for the pelvis and femur, and the coordinate systems were parallelized. Furthermore, their relationship with the modified HHS (mHHS) 1 year after THA was determined. Results: Significant correlations were found among mHHS, GFO, and SGL in the binomial group, whereas LLD was not significantly correlated. The optimal values of GFO and SGL were 1.01 mm and 0.18 mm/100 cm body height, respectively, which were considered optimal when the SGL values were approximately equal to those of the non-operative side. The optimal ranges for GFO and SGL were -1.65 to 3.67 mm and -4.78 to 5.14 mm/100 cm, respectively. Conclusions: Our findings were obtained after adjusting the pelvis and femur to a unified coordinate system. Therefore, the results of this study can be directly applied to 3D planning.

Determining the clinicopathological significance of the VI-RADS ≧4 group: a retrospective study.

BACKGROUND: The Vesical Imaging Reporting and Data System (VI-RADS) is widely used for predicting muscle-invasive bladder cancer (MIBC). This study aimed to determine the clinicopathological significance of the VI-RADS ≧4 (VI≧4) group. METHODS: Patients who underwent transurethral resections of bladder tumors during the study period and preoperative magnetic resonance imaging were considered. The patients were pathologically diagnosed with urothelial carcinoma (UC). We first compared the results of patients with VI-RADS scores of 3 and 4 to determine the cut-off score for MIBC; thereafter, the patients were divided into the VI≧4 and VI-RADS ≦3 (VI≦3) groups using VI-RADS. The clinicopathological significance of the VI≧4 group was examined retrospectively by comparing the characteristics of each group. RESULTS: In total, 121 cases were examined, of which 28 were pathologically diagnosed with MIBC. Of the 28 MIBC cases, three (10.7%) had a VI-RADS score of ≦3, and 25 (89.3%) had a VI-RADS score of ≧4. Of the 93 NMIBC cases, 86 (92.5%) had a VI-RADS score of ≦3, and seven (7.5%) had a VI-RADS score of ≧4. The diagnostic performance of the VI-RADS with a cut-off score of 4 was 89.3% for sensitivity, 92.5% for specificity, and an area under the curve (AUC) of 0.91. Contrastingly, for a cut-off score of 3, the sensitivity was 89.3%, specificity was 62.0%, and AUC was 0.72. A VI-RADS score of ≥ 4 could predict MIBC. In the VI≧4 group, 30 of 32 (93.8%) patients had high-grade tumors. The VI≧4 group had significantly more high-grade bladder cancers than the VI≦3 group (p < 0.001 OR = 31.77 95%CI:8.47-1119.07). In addition, the VI≧4 group had more tumor necrosis (VI≧4 vs VI≦3, p < 0.001 OR = 7.46 95%CI:2.61-21.34) and more UC variant cases (VI≧4 vs VI≦3, p = 0.034 OR = 3.28 95%CI:1.05-10.25) than the VI≦3 group. CONCLUSIONS: This study suggests that VI-RADS has a high diagnostic performance in predicting MIBC and that VI-RADS could diagnose high-grade tumors, necrosis, and UC variants.

Semantic and Geometric-Aware Day-to-Night Image Translation Network.

Autonomous driving systems heavily depend on perception tasks for optimal performance. However, the prevailing datasets are primarily focused on scenarios with clear visibility (i.e., sunny and daytime). This concentration poses challenges in training deep-learning-based perception models for environments with adverse conditions (e.g., rainy and nighttime). In this paper, we propose an unsupervised network designed for the translation of images from day-to-night to solve the ill-posed problem of learning the mapping between domains with unpaired data. The proposed method involves extracting both semantic and geometric information from input images in the form of attention maps. We assume that the multi-task network can extract semantic and geometric information during the estimation of semantic segmentation and depth maps, respectively. The image-to-image translation network integrates the two distinct types of extracted information, employing them as spatial attention maps. We compare our method with related works both qualitatively and quantitatively. The proposed method shows both qualitative and qualitative improvements in visual presentation over related work.

Real-World Insights into Efficacy and Safety of Enfortumab Vedotin in Japanese Patients with Metastatic Urothelial Carcinoma: Findings, Considerations, and Future Directions.

This study presents the enfortumab vedotin (EV) treatment analysis at our institution. We retrospectively analyzed patients with metastatic urothelial cancer (mUC) treated with EV between January 2021 and October 2023. EV was administered at 1.25 mg/kg on days 1, 8, and 15 in a 28-day cycle. Whole-body computed tomography scans were performed to assess the treatment response. Patient characteristics, treatment histories, response rates, progression-free survival, and adverse events were evaluated. Response rates were determined, and adverse events were recorded. Among the 20 patients, 70% were male and 65% had bladder tumors. Most patients had lung (65%) or lymph node (65%) metastases. The median follow-up was 11.2 months, with 45% of the patients succumbing to the disease. The overall response rate was 55%. The median progression-free and median overall survivals were 10.5 and 12.9 months, respectively. Severe adverse events occurred in 35% of patients. In this real-world study, EV demonstrated promising efficacy and manageable safety profiles in Japanese patients with mUC. The study's results were consistent with previous clinical trials, although a longer follow-up was required. Our findings support EV use as a treatment option for patients with mUC who exhibit disease progression after platinum-based chemotherapy and immune-checkpoint inhibitor therapy.

Usefulness of the spectral shaping dual-source computed tomography imaging technique in posterior corrective fusion for adolescent idiopathic scoliosis.

PURPOSE: Since childhood exposure to radiation has been demonstrated to increase cancer risk with increase in radiation dose, reduced radiation exposure during computed tomography (CT) evaluation is desired for adolescent idiopathic scoliosis (AIS). Therefore, this retrospective study aimed to investigate the radiation dose of dual-source CT using a spectral shaping technique and the accuracy of the thoracic pedicle screw (TPS) placement for posterior spinal fusion (PSF) in patients with AIS. METHODS: Fifty-nine female patients with thoracic AIS who underwent PSF using CT-guided TPSs were included and divided into two groups comprised of 23 patients who underwent dual-source CT (DSCT) with a tin filter (DSCT group) and 36 who underwent conventional multislice CT (MSCT group). We assessed the CT radiation dose using the CT dose index (CTDIvol), effective dose (ED), and accuracy of TPS insertion according to the established Neo's classification. RESULTS: The DSCT and MSCT groups differed significantly (p < 0.001) in the mean CTDIvol (0.76 vs. 3.31 mGy, respectively) and ED (0.77 vs. 3.47 mSv, respectively). Although the correction rate of the main thoracic curve in the DSCT group was lower (65.7% vs. 71.2%) (p = 0.0126), the TPS accuracy (Grades 0-1) was similar in both groups (381 screws [88.8%] vs. 600 screws [88.4%], respectively) (p = 0.8133). No patient required replacement of malpositioned screws. CONCLUSION: Spectral shaping DSCT with a tube-based tin filter allowed a 75% radiation dose reduction while achieving TPS insertion accuracy similar to procedures based on conventional CT without spectral shaping.

A case of renal abscess mimicking metastatic lesion in a patient with lung carcinosarcoma.

Renal abscesses require prompt diagnosis and appropriate intervention, as they can be life-threatening. However, diagnosis based solely on clinical findings is often challenging. We present the case of a 69-year-old woman with left renal masses on follow-up computed tomography (CT) after surgery for pT2aN0M0 lung carcinosarcoma. The masses were localized only in the left kidney without suspected metastatic lesions at other sites. The patient was referred to our department for further evaluation and treatment under a diagnosis of suspected metastatic lung carcinosarcoma of the left kidney. On enhanced CT, the left renal masses, the largest of which had a diameter of 40×36 mm had thick irregular walls gradually enhanced by the contrast media and an internal low-attenuation area. The masses showed heterogeneous signal intensity with a pseudocapsule on T2-weighted magnetic resonance imaging. Clinical symptoms such as fever or costovertebral angle tenderness were absent, and blood and urine tests were not sufficiently inflammatory to suggest a renal abscess. Histopathological findings on CT-guided renal biopsy revealed only inflammatory tissue and no tumor cells. However, because lung carcinosarcoma metastatic nodules could not be ruled out, laparoscopic left nephrectomy was performed for a definitive diagnosis and curative intent. The pathological diagnosis was renal abscess without malignant lesions. Here, we present a case of renal abscess mimicking metastatic lesions in a patient with lung carcinosarcoma. Accurately differentiating renal abscesses from metastatic renal tumors before treatment is often difficult. Renal abscess diagnosis should be considered through a comprehensive evaluation of the clinical findings of individual cases.

A case of marked rectal stenosis due to Douglas' pouch metastasis of renal pelvic carcinoma successfully treated with salvage enfortumab vedotin: correlation between serum KL-6 levels and tumor response.

Introduction: We report a rare case of marked rectal stenosis due to Douglas' pouch metastasis of renal pelvic urothelial carcinoma successfully treated with enfortumab vedotin. Case presentation: A 77-year-old female presented with difficulty in defecation and abdominal distension. She had received two courses of cisplatin plus gemcitabine followed by four courses of maintenance avelumab for postoperative lymph node metastasis of renal pelvic urothelial carcinoma. KL-6 levels were elevated, and a computed tomography scan revealed an irregularly shaped large mass occupying Douglas' pouch, with marked rectal stenosis. Metastatic urothelial carcinoma was pathologically diagnosed, and enfortumab vedotin was initiated after colostomy. After 12 courses of enfortumab vedotin, metastatic lesions showed marked shrinkage and KL-6 levels decreased. Conclusion: Enfortumab vedotin elicited a remarkable response in treating rectal stenosis due to metastasis of renal pelvic urothelial carcinoma in Douglas' pouch. Furthermore, serum KL-6 levels were correlated with the severity of metastatic urothelial carcinoma.

Primary leiomyoma of the bladder radiologically mimicking a retroperitoneal tumor - a case report.

The case presented is of a 47-year-old patient with an extravesical pedunculated bladder leiomyoma, which was difficult to distinguish from a retroperitoneal tumor. Preoperatively, it was suspected to be a retroperitoneal tumor and a laparotomy with tumor resection was performed. lntraoperatively, the bladder and tumor were connected by a cord-like tissue. A retrospective review of preoperative images revealed that cord-like tissue, identified intraoperatively, was also present. Bladder leiomyomas can grow as extravesical pedunculated tumors. Therefore, when the continuity between the bladder and tumor is only a cord-like object, the finding ofcontinuity is useful to diagnose with bladder leiomyoma. J. Med. Invest. 70 : 513-515, August, 2023.

The effect of Dunaliella tertiolecta supplementation on diet-induced obesity in UCP1-deficient mice.

We previously demonstrated that dietary supplementation with Dunaliella tertiolecta (DT) increases uncoupling protein 1 (UCP1) expression in brown adipose tissue (BAT) and improves diet-induced obesity (DIO) in C57BL/6 J mice at thermoneutrality (30 °C). Here, we investigated whether DT improves DIO in a thermoneutral UCP1-deficient (KO) animal. KO mice were fed a high-fat diet supplemented with DT for 12 weeks. Compared to control group without DT, body weight was significantly reduced in DT group with no difference in food intake. Dunaliella tertiolecta-supplemented mice exhibited lower adiposity and well-maintained multilocular morphology in BAT, in which a significant increase in gene expression of PR domain containing 16 was detected in DT group compared to control group. Moreover, increase in UCP2 level and/or decrease in ribosomal protein S6 phosphorylation were detected in adipose tissues of DT group relative to control group. These results suggest that DT supplementation improves DIO by stimulating UCP1-independent energy dissipation at thermoneutrality.

Perirenal fat stranding as a predictor of disease progression after radical nephroureterectomy for renal pelvic urothelial carcinoma: a retrospective study.

BACKGROUND: To investigate the impact of Perirenal fat stranding (PRFS) on progression after radical nephroureterectomy (RNU) for renal pelvic urothelial carcinoma (RPUC) without hydronephrosis and to reveal the pathological findings of PRFS. METHODS: Clinicopathological data, including computed tomography (CT) findings of the ipsilateral PRFS, were collected from the medical records of 56 patients treated with RNU for RPUC without hydronephrosis between 2011 and 2021 at our institution. PRFS on CT was classified as either low or high PRFS. The impact of PRFS on progression-free survival (PFS) after RNU was analyzed using the Kaplan-Meier method and log-rank test. In addition, specimens including sufficient perirenal fat from patients with low and with high PRFS were pathologically analyzed. Immunohistochemical analysis of CD68, CD163, CD3, and CD20 was also performed. RESULTS: Of the 56 patients, 31(55.4%) and 25 (44.6%) patients were classified as having low and high PRFS, respectively. Within a median follow-up of 40.6 months postoperatively, 11 (19.6%) patients showed disease progression. The Kaplan-Meier method and log-rank test revealed that patients with high PRFS had significantly lower PFS rates than those with low PRFS (3-year PFS 69.8% vs 93.3%; p = 0.0393). Pathological analysis revealed that high PRFS specimens (n = 3 patients) contained more fibrous strictures in perirenal fat than low PRFS specimens (n = 3 patients). In addition, M2 macrophages (CD163 +) infiltrating fibrous tissue in perirenal area were observed in all patients with high PRFS group. CONCLUSIONS: PRFS of RPUC without hydronephrosis consists of collagenous fibers with M2 macrophages. The presence of ipsilateral high PRFS might be a preoperative risk factor for progression after RNU for RPUC patients without hydronephrosis. Prospective studies with large cohorts are required in the future.

Deep Voxelized Feature Maps for Self-Localization in Autonomous Driving.

Lane-level self-localization is essential for autonomous driving. Point cloud maps are typically used for self-localization but are known to be redundant. Deep features produced by neural networks can be used as a map, but their simple utilization could lead to corruption in large environments. This paper proposes a practical map format using deep features. We propose voxelized deep feature maps for self-localization, consisting of deep features defined in small regions. The self-localization algorithm proposed in this paper considers per-voxel residual and reassignment of scan points in each optimization iteration, which could result in accurate results. Our experiments compared point cloud maps, feature maps, and the proposed map from the self-localization accuracy and efficiency perspective. As a result, more accurate and lane-level self-localization was achieved with the proposed voxelized deep feature map, even with a smaller storage requirement compared with the other map formats.

Development of an osteosarcoma model with MYCN amplification and TP53 mutation in hiPS cell-derived neural crest cells.

Mesenchymal stem cell- or osteoblast-derived osteosarcoma is the most common malignant bone tumor. Its highly metastatic malignant phenotypes, which are often associated with a poor prognosis, have been correlated with the modulation of TP53- and cell-cycle-related pathways. MYC, which regulates the transcription of cell-cycle modulating genes, is used as a representative prognostic marker for osteosarcoma. Another member of the MYC oncoprotein family, MYCN, is highly expressed in a subset of osteosarcoma, however its roles in osteosarcoma have not been fully elucidated. Here, we attempted to create an in vitro tumorigenesis model using hiPSC-derived neural crest cells, which are precursors of mesenchymal stem cells, by overexpressing MYCN on a heterozygous TP53 hotspot mutation (c.733G>A; p.G245S) background. MYCN-expressing TP53 mutated transformed clones were isolated by soft agar colony formation, and administered subcutaneously into the periadrenal adipose tissue of immunodeficient mice, resulting in the development of chondroblastic osteosarcoma. MYCN suppression decreased the proliferation of MYCN-induced osteosarcoma cells, suggesting MYCN as a potential target for a subset of osteosarcoma treatment. Further, comprehensive analysis of gene expression and exome sequencing of MYCN-induced clones indicated osteosarcoma-specific molecular features, such as the activation of TGF-ß signaling and DNA copy number amplification of GLI1. The model of MYCN-expressing chondroblastic osteosarcoma was developed from hiPSC-derived neural crest cells, providing a useful tool for the development of new tumor models using hiPSC-derived progenitor cells with gene modifications and in vitro transformation.

Vesicocutaneous fistula due to vesical diverticulitis with stones: A case report and literature review.

Introduction: We encountered an extremely rare case of a vesicocutaneous fistula due to vesical diverticulitis with stones. Case presentation: A 78-year-old male patient presented to our department with complaints of suppurative discharge in the suprapubic area. Computed tomography revealed an enlarged prostate, a vesical diverticulum with stones located on the ventral side, and an aberrant connection between the anterior bladder wall and the external surface of the skin. The patient was diagnosed with a vesicocutaneous fistula due to vesical diverticulitis and was successfully treated with a multidisciplinary approach including vesical diverticulectomy with stone removal and nonviable tissue debridement. The patient continues to receive regular outpatient follow-ups with urinary catheter changes. Conclusion: Vesicocutaneous fistulas due to vesical diverticulitis with stones are extremely rare. We should be aware that a vesical diverticulum with stones located on the ventral side might pose a high-risk factor for the formation of a vesicocutaneous fistula in elderly patients.

CREG1 stimulates AMPK phosphorylation and glucose uptake in skeletal muscle cells.

The cellular repressor of adenovirus early region 1A-stimulated gene 1 (CREG1) is a secreted glycoprotein involved in cell differentiation and energy metabolism. It also binds to insulin-like growth factor 2 receptor (IGF2R), a protein implicated in muscle regeneration. However, whether CREG1 regulates the regeneration and metabolism of skeletal muscles via IGF2R remains unclear. This study investigates the role of CREG1 in skeletal muscle regeneration and glucose uptake in C2C12 myotubes and a cardiotoxin (CTX)-induced mouse skeletal muscle regeneration model. CTX-treated skeletal muscle showed significantly higher levels of IGF2R, CREG1, phospho-AMPKα Thr172, and GLUT4 proteins. Similarly, treatment of myotubes with CREG1 also stimulated AMPKα phosphorylation and GLUT4 expression. CREG1-induced AMPKα phosphorylation and 2DG uptake in myotubes were suppressed by IGF2R knockdown and Compound C, an AMPK inhibitor. These results suggest that CREG1 stimulates glucose uptake in skeletal muscles partially through AMPK activation. Hence, CREG1 plays an essential role in muscle regeneration by affecting glucose metabolism in skeletal muscles.

Polycomb EZH1 regulates cell cycle/5-fluorouracil sensitivity of neuroblastoma cells in concert with MYCN.

In the present study, we found that EZH1 depletion in MYCN-amplified neuroblastoma cells resulted in significant cell death as well as xenograft inhibition. EZH1 depletion decreased the level of H3K27me1; the interaction and protein stabilization of MYCN and EZH1 appear to play roles in epigenetic transcriptional regulation. Transcriptome analysis of EZH1-depleted cells resulted in downregulation of the cell cycle progression-related pathway. In particular, Gene Set Enrichment Analysis revealed downregulation of reactome E2F-mediated regulation of DNA replication along with key genes of this process, TYMS, POLA2, and CCNA1. TYMS and POLA2 were transcriptionally activated by MYCN and EZH1-related epigenetic modification. Treatment with the EZH1/2 inhibitor UNC1999 also induced cell death, decreased H3K27 methylation, and reduced the levels of TYMS in neuroblastoma cells. Previous reports indicated neuroblastoma cells are resistant to 5-fluorouracil (5-FU) and TYMS (encoding thymidylate synthetase) has been considered the primary site of action for folate analogues. Intriguingly, UNC1999 treatment significantly sensitized MYCN-amplified neuroblastoma cells to 5-FU treatment, suggesting that EZH inhibition could be an effective strategy for development of a new epigenetic treatment for neuroblastoma.

Differential diagnosis and prognosis of small renal masses: association with collateral vessels detected using contrast-enhanced computed tomography.

BACKGROUND: Active surveillance (AS) is one of the treatment methods for patients with small renal masses (SRMs; < 4 cm), including renal cell carcinomas (RCCs). However, some small RCCs may exhibit aggressive neoplastic behaviors and metastasize. Little is known about imaging biomarkers capable of identifying potentially aggressive small RCCs. Contrast-enhanced computed tomography (CECT) often detects collateral vessels arising from neoplastic angiogenesis in RCCs. Therefore, this study aimed to evaluate the association between SRM differential diagnoses and prognoses, and the detection of collateral vessels using CECT. METHODS: A total of 130 consecutive patients with pathologically confirmed non-metastatic SRMs (fat-poor angiomyolipomas [fpAMLs; n = 7] and RCCs [n = 123]) were retrospectively enrolled. Between 2011 and 2019, SRM diagnoses in these patients were confirmed after biopsy or surgical resection. All RCCs were surgically resected. Regardless of diameter, a collateral vessel (CV) was defined as any blood vessel connecting the tumor from around the kidney using CECT. First, we analyzed the role of CV-detection in differentiating between fpAML and RCC. Then, we evaluated the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of RCC diagnosis based on CV-detection using CECT. We also assessed the prognostic value of CV-detection using the Fisher exact test, and Kaplan-Meier method and the log-rank test. RESULTS: The sensitivity, specificity, PPV, NPV, and accuracy of CV-detection for the diagnosis of small RCCs was 48.5, 45.5, 100, 100, and 9.5% respectively. Five of 123 (4.1%) patients with RCC experienced recurrence. CV-detection using CECT was the only significant factor associated with recurrence (p = 0.0177). Recurrence-free survival (RFS) was significantly lower in patients with CV compared with in those without CV (5-year RFS 92.4% versus 100%, respectively; p = 0.005). In addition, critical review of the CT images revealed the CVs to be continuous with the venous vessels around the kidney. CONCLUSIONS: The detection of CVs using CECT is useful for differentiating between small fpAMLs and RCCs. CV-detection may also be applied as a predictive parameter for small RCCs prone to recurrence after surgical resection. Moreover, AS could be suitable for small RCCs without CVs.

Rhabdomyolysis after Retroperitoneal Laparoscopic Radical Nephrectomy in the Lateral Decubitus Position.

Postoperative rhabdomyolysis is a rare but potentially fatal surgical complication. We experienced a case of rhabdomyolysis after laparoscopic radical nephrectomy (LRN). Right renal carcinoma was diagnosed in a 31-year-old woman with a body mass index of 28.5 kg/m2. She underwent right retroperitoneal LRN in the lateral decubitus position. The operating time was approximately 5 hours. Immediately after surgery, she reported pain in the left buttock, and reddish discoloration of the urine was observed. On the basis of these symptoms, an elevated serum creatine kinase level, and computed tomography findings, we diagnosed rhabdomyolysis of the left gluteal muscle secondary to its intraoperative compression caused by prolonged placement in a fixed position. She was treated with hydration therapy and discharged 6 days postoperatively. Prolonged surgery, obesity, and placement in the lateral decubitus position are risk factors for postoperative rhabdomyolysis. Surgeons should attempt to reduce operating time for LRN when obese patients are placed in the lateral decubitus position.

Intraoperative Placement of an Absorbable Spacer Prior to Radiation Therapy for a Malignant Peripheral Nerve Sheath Tumor.

A 7-year-6-month-old female was diagnosed with a pelvic malignant peripheral nerve sheath tumor and lymph node metastases. Tumorectomy was performed after four cycles of chemotherapy. A 33-mm cystic lesion was observed around the left iliac muscle after three cycles of postoperative chemotherapy, and proton beam therapy (PBT) was recommended. She was referred for absorbable spacer (AS) placement. The left ovarian appendage (OA) was resected due to the direct tumor infiltration. The right OA was fixed to the uterosacral ligament. The AS was fixed to the lateral pelvis. The PBT (70.3 Gy relative biological effectiveness) was performed successfully with the AS, and she also had the reproducing possibility due to prevention of severe irradiation damage of the right OA. AS eliminated the surgical removal of spacers and enabled us high-dose PBT for residual tumor without severe irradiation damage including infertility.

Effect of concomitant use of G-CSF and myelosuppressive chemotherapy on bone marrow and peripheral granulocytes in a mouse model.

Granulocyte-colony stimulating factor (G-CSF) stimulates bone marrow progenitor cell proliferation and enhances neutrophil production. Exogenous G-CSF administration is indicated for chemotherapy-induced neutropenia management. However, there is a paucity of basic research examining the effects of the concomitant use of G-CSF and chemotherapy on myeloid cells in vivo. Whether concomitant G-CSF and chemotherapy adversely affect myeloid cell proliferation have not been determined. Herein, we examined the effects of the concomitant use of pegfilgrastim and 5-fluorouracil on myeloid cells and peripheral blood cells in mouse models. Balb/c mice were treated intraperitoneally with 5-fluorouracil (20 µg/g b.w.) or a vehicle as a control for 5 days, and pegfilgrastim was administered subcutaneously at 1 µg/g b.w. on day 3. As a result, we demonstrated that the concomitant use of pegfilgrastim suppressed the 5-fluorouracil-induced decrease of granulocytic cells in both bone marrow and peripheral blood in mice. To assess the clinical efficacy of early administration of pegfilgrastim during docetaxel, cisplatin, and 5-fluorouracil therapy in patients with esophageal cancer, we retrospectively identified 42 consecutive patients treated with this regimen. The incidence of both febrile neutropenia and grade 4 neutropenia was significantly lower in patients who received pegfilgrastim than in those who did not receive it (P = 0.002 and P = 0.002, respectively). These results suggest that the concomitant use of pegfilgrastim and chemotherapy, consisting of continuous infusions of 5-fluorouracil, improved chemotherapy-induced neutropenia without detrimental effects on proliferating myeloid granulocytic cells.