Search

Malignant gastrointestinal neuroectodermal tumors (GNETs) are mesenchymal tumors that typically arise in the digestive tract and harbor EWSR1::ATF1 or EWSR1::CREB1 fusions. We report a case of primary retroperitoneal GNET in a 38-year-old woman who presented with a month-long fever with increased serum IL-6 level. A right retroperitoneal mass of 7 cm consisting of diffuse sheets of small cells with a high nuclear-to-cytoplasmic ratio and scattered osteoclast-like multinucleated giant cells was confirmed apart from the digestive tract. Peripheral lymphoid cuff and focal pseudoangiomatous spaces were present, reminiscent of angiomatoid fibrous histiocytoma. The tumor cells were positive for S100 protein and SOX10 and negative for melanocytic markers. Fluorescent in situ hybridization revealed EWSR1 and CREM gene rearrangements, consistent with EWSR1::CREM fusion, which has never been reported in GNET. The patient lives with recurrent lesions for 8 months. This case was associated with several unusual features and contributes to the evolving GNET concept.

Birt-Hogg-Dubé syndrome is an autosomal dominant disease caused by germline mutations in the folliculin gene (FLCN), characterized by skin fibrofolliculomas, pulmonary cysts, and multiple renal tumors. We report the case of a 51-year-old woman with multiple bilateral renal tumors resected by bilateral open partial nephrectomy. Following pathological diagnosis of hybrid oncocytic/chromophobe tumors, targeted next-generation sequencing of FLCN of the patient's blood revealed a novel missense mutation (c.602AC, p.Gln201Pro) in exon 6. Sanger sequencing revealed that this mutation was heterozygous. In silico prediction programs consistently indicated the mutation as pathogenic. Western blot analysis and immunohistochemistry revealed suppressed FLCN expression and the upregulation of glycoprotein nonmetastatic B, a downstream target negatively regulated by FLCN, in the tumor tissue, suggesting that the mutation resulted in reduction of functional FLCN expression. Whole-genome sequencing of one of the tumors identified another frameshift mutation in exon 4, suggesting a "second hit" leading to tumorigenesis. We recommend that gene sequencing should be considered in patients with multiple renal tumors to identify their genetic predisposition to renal tumors.

We retrospectively analyzed the effect of lymph node dissection (LND) in patients with renal cell carcinoma (RCC). Of 151 patients who underwent nephrectomy for RCC, 86 underwent LND. No distant metastasis (M0) was present in 71 patients, although distant metastasis (M1) was present in 15. Three (4.2%) and eight (53%) patients in the M0 and M1 groups, respectively, were clinical N-stage positive. Two (2.8%) and three (20%) patients in the M0 and M1 groups, respectively, were pathological N-stage positive. Both pathological N stage-positive patients in the M0 group were pathologically diagnosed with microphthalmia transcription family translocation RCC. The clinical and pathological positive node areas exhibited concordance in all three pathological N stage-positive patients in the M1 group. Chylous leakage occurred in 16 (19%) patients in the LND group (p＜0.05). Extended LND was a statistically significant risk factor for chylous leakage in the multivariate analysis. Only limited cases should undergo LND, owing to the low frequency of positive pathological lymph node metastasis, and high complication rate.

A 36-year-old man presented to our hospital with right scrotal swelling. A computed tomographic scan revealed a mass in the right scrotum, multiple masses in the lung and liver, and enlarged cervical, mediastinal, and retroperitoneal lymph nodes. After right high orchiectomy, he was diagnosed with nonseminomatous germ cell tumor (pT3N3M1b), with poor risk prediction according to the International Germ Cell Consensus classification. We started chemotherapy with bleomycin, etoposide, and cisplatin. Since serum alphafetoprotein (AFP) and human chorionic gonadotropin (HCG) levels did not decrease to normal levels, second-line chemotherapy with paclitaxel, ifosfamide, and cisplatin was administered. Six days after the start of treatment, the patient became unconscious, and his blood pressure decreased. Seven days later, blood tests revealed high uric acid levels, hyperphosphatemia, and increased creatinine. This was diagnosed as tumor lysis syndrome. Following diagnosis, continuous hemodiafiltration was started, and his condition gradually improved.

This study investigated the efficacy of docetaxel (DOC) and cabazitaxel (CBZ) and examined the factors associated with the prognosis of patients with castration-resistant prostate cancer (CRPC) receiving DOC-CBZ sequential treatment in Japanese real-world data.We retrospectively evaluated data for 146 patients who received DOC followed by CBZ. The correlations of prostate specific antigen (PSA) decrease rate and time to progression between DOC and CBZ treatment were examined. Combined progression-free survival (PFS) of DOC-CBZ and overall survival (OS) from the initiation of DOC and the diagnosis of CRPC were evaluated and compared between patients with high and low PSA levels at the start of DOC and CBZ treatment.No correlations of PSA decrease rate and time to progression were observed between DOC and CBZ. The patients for whom DOC was started in higher PSA levels had significantly shorter combined PFS (p = 0.003) and OS from the initiation of DOC (p = 0.002). In patients who started DOC at high PSA levels, those who switched to CBZ at low PSA levels had longer OS than those who switched at high PSA levels (p = 0.048). The OS from CRPC of patients who started DOC at low PSA levels was significantly longer than those that started at high PSA levels (p = 0.030).For patients for whom DOC was not effective, sequential CBZ might have change to be effective. The PSA levels at the start of DOC and CBZ might be a potential prognostic biomarker.

Magnetic resonance imaging (MRI) ultrasound fusion biopsy is becoming popular owing to the better detection rate of clinically significant prostate cancer (csPCa). We retrospectively evaluated the accuracy of MRI-targeted biopsy during the period of introduction at a single academic center by comparing findings of its specimen and whole-mount histopathology. Between June 2018 and January 2021, 106 transperineal MRI-ultrasound fusion biopsies using BioJet software were performed. Among the cases, 15 subsequently underwent robotic-assisted laparoscopic radical prostatectomy and were eligible for analysis. This study included all regions of interest (ROIs) with a Prostate Imaging Reporting and Data System v2 category of 3 or greater on pre-biopsy MRI．For each lesion, grade group of MRI-targeted biopsy specimens and prostatectomy specimens were compared. From a total of 25 ROIs identified among 15 males, csPCa was found in 21 (84%) of the concordant locations of prostatectomy specimens. However, MRI-targeted biopsy could diagnose csPCa in only 12 (48%) of them. In the csPCa undetected group, the ROI volume was significantly smaller (median volume 0.23 ml vs 0.40 ml, p＝0.03). We also found that in cases where PCa was not detected through MRI-targeted biopsy, the biopsy sample length was significantly shorter (median length 9 mm vs 17 mm, p＝0.01). Our data suggest that failure of detecting PCa in MRI-targeted biopsy could be due to technical errors at the introduction period of the technique. A sufficient sampling length of 10 mm or more is desirable, especially for small lesions.

Background Renal transplantation improves the quality of life (QOL) of end-stage renal disease (ESRD) patients with renal failure. However, it remains unclear which renal disease-specific QOL aspects determine general health-related QOL of ESRD patients. This study aimed to identify these QOL items by examining the QOL of ESRD patients using the Kidney Disease Quality of Life-Short Form (KDQOL-SF), version 1.3, and EuroQoL-5 dimension-5 levels (EQ-5D-5L) questionnaires. Methods We conducted QOL surveys with 67 renal transplant recipients at our hospital. EQ-5D-5L, which evaluates general health-related QOL, was the response variable, and KDQOL-SF, which includes the renal disease-specific instrument and general health-related QOL SF-36 instrument, was the explanatory variable. We analyzed the effects of each KDQOL-SF domain on EQ-5D-5L using Pearson correlation coefficient. Results Regarding the general health-related QOL assessed by SF-36, physical health aspects, such as physical functioning (R = 0.749) and daily functioning physical (R = 0.603), showed a strong correlation with EQ-5D-5L, and the domains related to the psychological and social aspects of QOL showed a limited correlation. Regarding kidney disease-specific scales, symptoms/problems related to physical function showed a good correlation (R = 0.691) with EQ-5D-5L, whereas other scales, including burden of kidney disease (R = 0.168), quality of social interaction (R = 0.284), and those related to the mental and social aspects of QOL showed a low correlation with EQ-5D-5L. Conclusion Among kidney transplant recipients, the physical health aspects of QOL, such as symptoms/problems, were the major factors influencing overall QOL as assessed by EQ-5D-5L.

Objectives To assess the effect of optimal neoadjuvant chemotherapy of at least three cycles of cisplatin-based regimen on oncological outcomes of clinical stage T3 or higher bladder cancer treated with laparoscopic radical cystectomy. Methods Laparoscopic radical cystectomies carried out at 10 institutions were included in this retrospective study. The outcomes of patients who received optimal neoadjuvant chemotherapy and those who did not receive neoadjuvant chemotherapy were compared using propensity score matching in clinical stage T3-4 or T2 cohorts, separately. Results Of the 455 patients screened, matched pairs of 54 patients in the clinical T3-4 cohort and 68 patients in the clinical T2 cohort were finally analyzed. In the cT3-4 cohort, the 5-year overall survival (78% vs 41%; P = 0.014), cancer-specific survival (81% vs 44%; P = 0.008) and recurrence-free survival (71% vs 53%; P = 0.049) were significantly higher in the optimal neoadjuvant chemotherapy group than in the no neoadjuvant chemotherapy group; no significant survival difference was shown between the two groups in the cT2 cohort. In the cT3-4 cohort, the incidence of local recurrence (4% vs 26%; P = 0.025) and abdominal or intrapelvic recurrence, including peritoneal carcinomatosis (7% vs 30%; P = 0.038), was significantly lower in the optimal neoadjuvant chemotherapy group. Conclusions Administration of optimal neoadjuvant chemotherapy has a significant survival benefit. It decreases the incidence of local and atypical recurrence patterns in patients with clinical stage T3 or higher locally advanced bladder cancer undergoing laparoscopic radical cystectomy.

Purpose: Genomic profiling in urothelial carcinoma (UC) conventionally uses tissue DNA. However, tissue biopsy is so invasive that it can be difficult in some cases. Cell-free DNA (cfDNA) assay is a minimally invasive tool obtaining a comprehensive genomic information reflecting a tumor heterogeneity. Recently, the investigation of cfDNA assay in UC is widely conducted, but its clinical utility remains largely unknown. We aimed to establish plasma cfDNA assay and clarify its clinical role in UC. Method: Blood and matched tissue were obtained from 48 cases with advanced UC before 1st line systemic therapy or radical surgery. For genomic profiling of all samples, we applied a customed targeted DNA-sequencing strategy capturing 54 UC-relevant genes. Somatic mutations were required to be supported by a minimum variant allele frequency (VAF) of 0.5% in plasma cfDNA and 5% in tissue DNA. All mutation calls were filtered against matched leukocyte DNA. The result of mutational analysis was validated with digital PCR. The proportion of tumor-derived cfDNA (circulating tumor DNA (ctDNA) fraction) was estimated. We investigated the association between genomic profile and molecular subtyping with RNA sequencing and immunohistochemistry (IHC). Result: Fifty-five somatic mutations were detected in 22 cfDNA samples (22/48, 45.8%). Twenty-six of all somatic mutations identified in cfDNA (26/55, 47.3%) were concurrently present in tumor tissues. In 14 mutations randomly selected from all of those detected in cfDNA, VAF of digital PCR was statistically consisted with the result of NGS (p Conclusions: We established cfDNA assay for genome profiling in advanced UC. The result of validation using digital PCR suggested that cfDNA assay can identify the mutation which cannot be detected in tissue sample as a tumor heterogeneity. Additionally, cfDNA assay generate the information for classifying UC cases by molecular subtypes and predicting the expression of immune checkpoint molecules. Further investigation is needed as a promising minimally invasive assay to predict an immunotherapy responsiveness against metastatic UC. Citation Format: Yuki Kita, Takayuki Sumiyoshi, Takeshi Sano, Akihiro Hamada, Toru Sakatani, Kenji Nakamura, Hideaki Takada, Ryousuke Ikeuchi, Takayuki Goto, Atsuro Sawada, Shusuke Akamatsu, Takashi Kobayashi. Establishing clinical utility for genomic profiling with plasma cell free DNA in urothelial carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 235.

Background/aim Standard chemotherapy for advanced urothelial carcinoma (UC) patients with moderate renal dysfunction has not yet been established. Patients and methods We retrospectively assessed outcomes of patients with advanced UC who underwent first-line chemotherapy with full-/reduced-dose gemcitabine plus cisplatin (GC-f/GC-r) or full-/reduced-dose gemcitabine plus carboplatin (G-Car-f/G-Car-r) according to renal function. Results Seventy-eight patients were included in this study. The objective response rate was 42%, 30%, 42%, and 27% for the GC-f, GC-r, G-Car-f, and G-Car-r groups, respectively. For the GC-r and G-Car-f groups, the median progression-free survival and the median overall survival was 4.5 vs. 7.0 months (p=0.07) and 7.5 months vs. 12.0 months (p=0.124), respectively. Grade 3/4 thrombocytopenia occurred more frequently in the GC-r group than the G-Car-f group (80% vs. 38%, p=0.021). Conclusion G-Car-f could be more beneficial than GC-r for patients with advanced UC who have moderate renal dysfunction.

Background The clinical utility of 99mTc-mercaptoacetyltriglycine cortical renography for the prediction of graft function in kidney transplant recipients has been unknown. Methods We retrospectively reviewed post-transplant cortical renograms in 40 kidney transplant recipients. We analyzed the correlation between T1/2 (elimination half-life) and graft function (measured-to-expected glomerular filtration rate [GFR]) 1 week, and 1, 3, and 6 months post operation compared with whole-kidney renograms. Results Delayed drainage (T1/2 > 11 minutes) was observed in 22 recipients (55%). T1/2 and postoperative GFR ratio were inversely correlated (1 week: R2 = 0.317, P = .0002; 1 month: R2 = 0.206, P = .003; 3 months: R2 = 0.117, P = .031; 6 months: R2 = 0.161, P = .010). Recipients with delayed drainage had a significantly lower GFR ratio than those with normal drainage 1 week (median, 0.93 vs 1.32; P = .001), 1 month (median, 1.65 vs 2.23; P = .0010), 3 months (median, 1.55 vs 2.17; P = .041), and 6 months (median, 1.67 vs 2.34; P = .018) post operation, respectively. Whole-kidney renograms failed to discriminate recipients with lower GFR ratio at 1, 3, and 6 months. Conclusions T1/2 in post-transplant cortical renography was inversely correlated with early graft function and may predict early post-transplant graft function.

To investigate the correlation between tumor size changes during the initial 4 cycles of first-line chemotherapy and tumor shrinkage following 2 additional cycles of chemotherapy in patients with advanced urothelial carcinoma (aUC) who experienced disease control after initial chemotherapy.We retrospectively reviewed 128 patients with aUC who received first-line chemotherapy. We analyzed 51 patients with disease control (stable disease or better) at the end of the fourth cycle. Of these, 47 patients received 1 to 2 additional cycles of chemotherapy, whereas the remaining patients underwent observation. For patients who received additional chemotherapy, the change in tumor size after additional chemotherapy (cycles 5-6) was defined as "no shrinkage" (tumor growth), "minor shrinkage" (no tumor growth or ≤10% reduction in tumor size), or "shrinkage" (10% reduction in tumor size). Then, we investigated the relationship between the rate of tumor size change during the initial 4 cycles and that after additional chemotherapy.Of the patients who received additional chemotherapy, the change in tumor size was categorized as no shrinkage in 21 patients (44.7%), minor shrinkage in 18 patients (38.3%), and shrinkage in 8 patients (17%). Regarding predictors of tumor shrinkage after additional chemotherapy, the rate of tumor size change between the cycles 3 and 4 (area under the receiver operating characteristics curve = 0.642) was correlated with the trend of the tumor shrinkage (P = 0.009) and the likelihood of beneficial tumor shrinkage after additional chemotherapy (minor shrinkage + shrinkage; P = 0.02). However, the change in tumor size between cycles 1 and 2, cycles 1 and 4, or cycles 3 and 4 was not satisfactorily predictive of further tumor shrinkage because of substantial overlaps of the tumor size changes.Only a small subset of patients would have substantial tumor shrinkage by additional cycles after successful induction of 4 cycle chemotherapy. Tumor size dynamics during the initial 4 cycles of chemotherapy displayed limited ability to predict the subset of patients with further tumor shrinkage after additional chemotherapy. Therefore, it might be better to consider switch maintenance immunotherapy for patients who experience disease control after the fourth cycle of first-line chemotherapy.

Introduction Simultaneous liver and kidney transplantation is a life-saving procedure for patients with liver failure and irreversible renal dysfunction. However, some studies have reported the recovery of native renal function after simultaneous liver and kidney transplantation. Case presentation A 33-year-old woman initially underwent living-donor liver transplantation for liver failure. When graft liver failure developed, she also sustained acute renal failure and required continuous hemodiafiltration for 6 weeks. Simultaneous liver and kidney transplantation from a brain-dead donor recovered her liver and renal function. A 1-year protocol graft kidney biopsy revealed acute cellular rejection despite stable serum creatinine levels. Renal scintigraphy showed functional native kidneys masking acute rejection of the graft kidney. The rejection was improved by pulse steroid therapy. Conclusion Acute rejection of the graft kidney may silently progress due to recovery of the native kidney function after simultaneous liver and kidney transplantation. Renal scintigraphy and graft kidney biopsy should be considered even if blood tests indicate stable total renal function.

Objectives To compare the perioperative and oncological outcomes of pure laparoscopic intracorporeal ileal conduit urinary diversion versus extracorporeal ileal conduit urinary diversion after laparoscopic radical cystectomy for bladder cancer in a multicenter cohort in Japan. Method A total of 455 patients who underwent laparoscopic radical cystectomy carried out at 10 institutions were included in this retrospective study. The perioperative data of the intracorporeal ileal conduit urinary diversion and extracorporeal ileal conduit urinary diversion groups were compared using the propensity score matching method. The Kaplan-Meier curves were obtained to elucidate time to ureteroenteric stricture, reoperation, recurrence and survival. Results In total, 72 matched pairs were evaluated for the final analysis. The median follow-up period was 28 and 23 months in the intracorporeal ileal conduit urinary diversion and extracorporeal ileal conduit urinary diversion groups, respectively. The operative time in the intracorporeal ileal conduit urinary diversion group was approximately 1 h longer than that in the extracorporeal ileal conduit urinary diversion group. The early and late postoperative complication rates were similar in both groups, except for the reduced wound-related complication rates in the intracorporeal ileal conduit urinary diversion group. The median days to regular oral food intake were 4 and 5 days in the intracorporeal ileal conduit urinary diversion and extracorporeal ileal conduit urinary diversion groups, respectively (P = 0.014). No significant difference was noted in the occurrence of ureteroenteric strictures and reoperation rate. Furthermore, recurrence-free, cancer-specific, and overall survival rates and recurrence patterns did not significantly differ. Conclusions Laparoscopic intracorporeal ileal conduit urinary diversion is a safe, feasible and reproducible procedure with similar postoperative complication rates, ureteroenteric stricture rate and oncological outcomes when compared with extracorporeal ileal conduit urinary diversion, but faster postoperative bowel recovery and decreased wound-related complication rates.

Objective To investigate oncological outcomes and recurrence patterns after laparoscopic radical cystectomy for bladder cancer in a Japanese multicenter cohort, and to explore the risk factors associated with recurrences due to tumor dissemination. Method Laparoscopic radical cystectomies carried out at 10 institutions were included in this retrospective study. Multivariate analyses were carried out to identify the clinical parameters associated with overall recurrences together with specific recurrence types. Kaplan-Meier curves were created to elucidate time to recurrence and survival. Results A total of 411 patients were included after the final analysis. Postoperative pathology was T2 or higher in 196 patients (48%), and lymph node metastasis was present in 46 patients (11%). The median follow-up period was 23 months, and the 2-year recurrence-free and cancer-specific survival rates were 71.0% and 84.7%, respectively. The recurrence sites involved distant metastasis in 75 patients (18%), local recurrence in 52 patients (13%) and urinary tract recurrence in eight patients (2%). When local recurrence at the cystectomy bed (28 patients; 7%) and abdominal recurrence including peritoneal carcinomatosis or port site recurrence (17 patients; 4%), which might be caused by tumor dissemination, were combined into a single group, prolonged surgical time was a significant risk factor, in addition to high pathological stage (T3-4 and/or positive lymph nodes), positive surgical margins, and variant histology by both univariate and multivariate analyses. Conclusions Our study findings suggest that recurrences after laparoscopic radical cystectomy might be caused by tumor dissemination, and attention should be paid to avoid prolonged surgical time in laparoscopic radical cystectomy.

Defective DNA mismatch repair genes can lead to microsatellite instability (MSI)-high status in prostate cancer (PC). Accumulation of replication errors in DNA leads to the production of abundant neoantigens, which could be targets for immune checkpoint inhibitors (CPIs). However, the incidence of MSI-high PC is low, and not all patients show a satisfactory therapeutic response to CPIs. Here, we present the case of a patient with MSI-high castration-resistant PC who showed a remarkable and durable response to pembrolizumab. The patient was resistant to abiraterone, docetaxel, and cabazitaxel and was suffering from multiple tumor-associated or treatment-related complications, such as urinary tract infection, infective endocarditis, and uncontrollable prostatic hemorrhage. Soon after the start of pembrolizumab therapy, the patient showed a dramatic decrease in prostate-specific antigen from 35.67 ng/mL to an undetectable level and a remarkable reduction in the size of a massive prostate mass and lymph node metastases, with an absence of treatment-related complications. Specimens from the transurethral resection of prostate cancer during cabazitaxel treatment for control of prostate bleeding and also that from the prostate biopsy at initial diagnosis revealed MSI-high status. Immunohistochemistry showed loss of MSH2 and MSH6, and whole-exome sequencing revealed an approximate tumor mutation burden of 61 mutations/Mb as well as biallelic loss of MSH2. Pembrolizumab could show a significant effect even in a heavily treated patient with MSI-high advanced PC. Accumulation of detailed clinical and genomic information of cases of MSI-high PC treated with pembrolizumab is necessary for optimal patient selection.

Simple Summary Pembrolizumab, an immune checkpoint inhibitor, has shown therapeutic benefit for advanced urothelial carcinoma (aUC) patients, but only a limited population achieves a long-term response. Prediction of treatment outcomes for aUC patients receiving immune checkpoint inhibitors is a clinical challenge. We assessed the associations between the expression of multiple immune markers in the tumor microenvironment using immunohistochemistry of tumor tissues obtained from 26 aUC patients who received second-line pembrolizumab treatment. We found that high infiltration of CD8-positive lymphocytes was significantly associated with a favorable objective response and overall and progression-free survival. Furthermore, expression of interferon-gamma (IFNγ) showed a significant positive correlation with post-progression survival. Finally, we demonstrated that the coincidence of low infiltration of CD8-positive lymphocytes and low IFNγ expression was an independent prognostic factor for an unfavorable response to pembrolizumab. Abstract Although immune checkpoint inhibitors have shown benefit for advanced urothelial carcinoma (aUC) patients, prognostication of treatment efficacy and response duration remains a clinical challenge. We evaluated the expression of immune markers in the tumor microenvironment and assessed their associations with response to and survival after pembrolizumab treatment in 26 aUC patients. High levels of CD8+ tumor-infiltrating lymphocytes (TILs) were associated with favorable objective responses (23.0% vs. 15.3%, p = 0.0425), progression-free survival (median, 8.8 vs 2.1 months; hazard ratio (HR), 0.24; 95% confidence interval (CI), 0.07–0.66, p = 0.0060), and overall survival (median, >24.0 vs. 5.3 months; HR, 0.17; 95% CI, 0.04–0.56, p = 0.0034) compared with low levels. High interferon-gamma (IFNγ) expression levels were associated with longer post-progression survival (median, 4.9 vs. 1.0 months; HR, 0.18; 95% CI, 0.04–0.59, p = 0.0027) compared with low expression. Multivariate analysis incorporating clinical prognosticators demonstrated that the coincidence of low CD8+ T cells/IFNγ was an independent factor for unfavorable overall survival after pembrolizumab treatment (HR, 4.07; 95% CI, 1.36–12.73; p = 0.0125). The combination of low CD8+ TILs and IFNγ expression was an independent prognostic factor with predictive ability equivalent to previously reported clinical prognosticators.

A 62-year-old man underwent left radical nephrectomy for left renal cell carcinoma at our hospital in 1999. At the age of 79 years, he was diagnosed with intra-abdominal disseminations, lung metastases, pancreas metastases, and bilateral femoral muscle metastases during a routine follow-up computed tomography scan. The patient began treatment with pazopanib. Four years later, at the age of 83 years, he developed fever, abdominal pain, and general malaise. Blood samples showed liver dysfunction, hypoalbuminemia, and anemia. Contrast-enhanced computed tomography showed thickening of the small bowel wall with marked edema of the submucosa from the third part of the duodenum to the jejunum, suggesting intestinal lymphangiectasia. The diagnosis of intestinal lymphangiectasia was confirmed by small bowel endoscopy and histological examination. The patient’s general condition improved after discontinuation of pazopanib without the need for any active therapeutic interventions. The possibility of intestinal lymphangiectasia should be considered in patients with hypoalbuminemia and general malaise during treatment with multikinase inhibitors.

A man in his 60s was diagnosed with clear cell carcinoma of the right kidney with multiple lung metastases, tumor thrombus of the inferior vena cava (IVC), and invasion of the duodenum and pancreas. Ipilimumab plus nivolumab was administered as first-line therapy. After 3 treatment courses, computed tomography (CT) demonstrated a slight decrease in the size of the primary tumor and lung metastases. However, the patient became hemodynamically unstable due to persistent duodenal bleeding during treatment despite frequent blood transfusions. Axitinib was then initiated as second-line therapy. The duodenal bleeding ceased 10 days after starting axitinib and his anemia remissed. Subsequent CT showed further decrease in the size of the primary tumor and lung metastases. The patient underwent right nephrectomy after improvement of nutrition. IVC thrombectomy, and pancreaticoduodenectomy. The lung metastases disappeared on postoperative imaging and no additional treatment was provided. Twelve months after surgery, he was in good health and showed no signs of recurrence.

A 22-year-old woman was referred to our hospital for further examination of an incidentally discovered hypervascular pelvic tumor with a maximum diameter of 10 cm. Although Castleman disease was suspected based on the imaging findings and pathologic findings of the needle biopsy, a definitive diagnosis was not made. Preoperative transcatheter arterial embolization was performed to decrease intraoperative bleeding, and tumor resection was performed on the following day. As for posterior approach prior to anterior approach, the patient was placed in a prone position, and the dorsal aspect of tumor was approached through the dissection of gluteal muscles. Then, dilated branches of the internal iliac vein was found on the tumor capsule, which were safely ligated under direct vision with favorable visual field. Then, the patient was placed in a supine position, the tumor was completely resected by anterior approach without transfusion. Histopathological diagnosis was Castleman disease hyaline vascular type. The patient was discharged without complication and has been free from recurrence for 6 months after surgery.

Physiologically based pharmacokinetic (PBPK) modeling is useful for evaluating differences in drug exposure among special populations, but it has not yet been employed to evaluate the absorption process of tacrolimus. In this study, we developed a minimal PBPK model with a compartmental absorption and transit model for renal transplant patients using available data in the literature and clinical data from our hospital. The effective permeability value of tacrolimus absorption and parameters for the single adjusting compartment were optimized via sensitivity analyses, generating a PBPK model of tacrolimus for renal transplant patients with good predictability. Next, we extrapolated the pharmacokinetics of tacrolimus for liver transplant patients by changing the population demographic parameters of the model. When the physiological parameters of a population with normal liver function were changed to those of a population with impaired hepatic function (Child-Pugh class A) in the constructed renal transplant PBPK model, the predicted tacrolimus concentrations were consistent with the observed concentrations in liver transplant patients. In conclusion, the constructed tacrolimus PBPK model for renal transplant patients could predict the pharmacokinetics in liver transplant patients by slightly reducing the hepatic function, even at three weeks post-transplantation.

Introduction Clinical recurrence of prostate cancer after curative treatment with a limited number of metastases is often termed as oligorecurrence. We report a case of solitary recurrence of prostate cancer surrounded by epithelium of the seminal vesicle or vas deferens. Case presentation A 54-year-old man diagnosed with localized prostate cancer underwent radiation therapy. Six years later, imaging studies detected a solitary recurrence. We performed metastasectomy, and histopathological examination revealed the metastatic lesion surrounded by the epithelium of the seminal vesicle or vas deferens. Surgical resection achieved a complete biochemical response. Conclusion We presented with a case of prostate cancer metastasis surrounded by the epithelium of the seminal vesicle or vas deferens.

Introduction Carboplatin and paclitaxel (CP) had shown moderate efficacy in treating castration-resistant prostate cancer (CRPC) before standard first-line docetaxel chemotherapy became available. Currently, for patients with homology-directed repair gene defects as well as for unselected patients, platinum chemotherapy is administered after all standard treatments have been ineffective. Here, we retrospectively studied the efficacy and safety of CP administered as the first-, second-, and third-line chemotherapy in patients with CRPC. Patients and Methods A retrospective chart review was performed for 58 patients with CRPC who received CP between 2001 and 2018 in a single institution. Twenty-seven patients received CP as the first-line chemotherapy, 21 as the second-line after docetaxel, and 10 as the third-line after docetaxel and cabazitaxel. Prostate-specific antigen (PSA) responses (> 50% decline of PSA from baseline), progression-free survival, overall survival, and adverse events were examined. Results PSA responses at any time were 55.6%, 19.0%, and 10.0%; PSA responses at 12 weeks were 48.1%, 14.3%, and 10.0%; the median progression-free survival was 3, 1, and 1 month; and the median overall survival was 19, 11, and 6 months, respectively, for the first-, second-, and third-line settings. The only patient who achieved exceptional and durable PSA response in the third-line setting had a deleterious germline BRCA2 mutation (5645C>A). The adverse event profile was favorable. Conclusion CP shows moderate efficacy against CRPC in the first-line setting, but shows little effect in the third-line setting. CP after docetaxel and cabazitaxel may be recommended in selected patients with CRPC with homology-directed repair gene defects.

This study aimed to describe the morbidity and mortality in older patients undergoing laparoscopic radical cystectomy (LRC) and compare the outcomes of LRC between octogenarians and younger patients ( 80 years) in a Japanese multicenter cohort.We identified 433 patients (80 octogenarians) who underwent LRC in a retrospective multicenter database from 10 institutions. The perioperative outcomes and the 90-day and late ( 90-day) complications according to the Clavien-Dindo classification were compared between the octogenarians and younger patients. Recurrence-free survival (RFS), overall survival (OS), and cancer-specific survival (CSS) were measured by the Kaplan-Meier method.Compared with the younger group, the octogenarian group included a significantly higher proportion of women, patients with a lower body mass index, patients with a lower preoperative albumin level, and patients with a history of abdominal surgery. The 90-day rates of all complications and major complications (grades III-V) were 50.0% and 20.0% among octogenarians and 54.7% and 16.4% among younger patients. The 90-day mortality rate among octogenarians was 3.8%. The 2-year RFS, CSS, and OS rates for octogenarians stratified by pathological stage was 95.2, 100, and 100% for ≤ pT1; 50.7, 76.6, and 56.1% for pT2; 33.6, 82.5, and 72.6% for ≥ pT3; and 23.1, 42.2, and 37.5% for pN + or distant metastasis, respectively. There was significant difference between octogenarians and younger patients only in 2-year OS for pT2 (56.1% vs 87.7%, p = 0.03).This study revealed that LRC can be performed for selected octogenarians with a complication rate similar to that of younger patients. Appropriate risk evaluation and modification of surgical procedures are necessary for octogenarians.

Recipients of organ transplants are immunosuppressed and at high risk of oral infection. Oral diseases are often neglected compared with infections of other organs that typically confer higher morbidity. However, severe local symptoms hinder oral intake, decrease quality of life, and are sometimes lethal. Here we describe a case of a 57-year-old woman who developed recurrent aphthous stomatitis after kidney transplantation; the cause of the infection was complex and included cytomegalovirus, herpes simplex virus, and Candida species. Since misdiagnosis of oral diseases impairs patient quality of life and increases morbidity, clinicians should be aware of possible etiologies of oral infections in renal transplant recipients.

Objectives To describe the complications and their surgical management after laparoscopic radical cystectomy in a Japanese multicenter cohort. Methods The participants were drawn from a retrospective multicenter study at 10 institutions. We identified 436 patients who underwent laparoscopic radical cystectomy with no robot assistance. Early and late complications were graded according to their Clavien-Dindo classification. The records of all patients who underwent surgical interventions for laparoscopic radical cystectomy-specific complications were also reviewed. Kaplan-Meier curves were used to describe the time to surgical intervention. Results The 90-day rates for overall complications, high-grade complications (Clavien-Dindo classification III-V) and mortality were 53%, 17% and 1.4%, respectively. Gastrointestinal (25%), infectious (22%) and abdominal wall-related (9%) complications were the most common. The late complication rate was 18%, and a total of 81 patients (19%) underwent surgical intervention during the median follow-up period of 22 months. The reoperation rate was 25% at 5 years. Gastrointestinal complications in the early postoperative period and abdominal wall-related complications in the late postoperative period were the main reasons for reoperation. Seven (7%) out of 100 female patients underwent emergent surgical reoperation for transvaginal bowel evisceration as a result of vaginal dehiscence. Conclusions Early and late postoperative complications and surgical reoperations are notable after laparoscopic radical cystectomy. Abdominal wall-related complications including vaginal dehiscence are common, and they represent the main indication for reoperation during long-term follow up.