Ureteroscopy for urolithiasis in bedridden patients: it is feasible and acceptable.

PURPOSE: To investigate the safety of transurethral ureteroscopy (URS) for urolithiasis in bedridden patients and to identify bedridden patient-specific risk factors for postoperative complications. METHODS: The patients who underwent URS for urolithiasis were divided into bedridden patients and good performance status (PS) patients, and the groups were compared regarding their clinical characteristics and postoperative complications. A multivariable logistic regression analysis was performed to evaluate independent predictors of postoperative febrile urinary tract infection (fUTI). RESULTS: A total of 1626 patients were included, 276 in the bedridden patient group, and 1350 in the good PS patient group. The bedridden patient group had a significantly higher age and higher proportion of females and had multiple comorbidities. In 77 patients (27.9%), 88 postoperative complications developed for the bedridden patient group. Clavien-Dindo grade III or IV complications were observed in only 8 patients. No grade V complications were observed. The most common complication was fUTI. The frequency of fUTI with grade III or IV for the bedridden patient group (2.2%) was higher compared with the good PS patient group (0.5%), but the difference was not statistically significant (p = 0.13). Bedridden patient-specific risk factors for fUTI included female sex, diabetes mellitus, cerebrovascular comorbidities, lower extremity contracture, and prolonged operative time. CONCLUSION: URS for urolithiasis is a feasible and acceptable procedure in bedridden patients, despite the moderate rate of postoperative complications. The identified risk factors provide a framework for risk stratification and individualized care in this unique patient population.

Hydronephrosis severity as a predictor of postoperative renal function decline following laparoscopic radical nephroureterectomy.

BACKGROUND: This study aimed to investigate factors, including the degree of hydronephrosis, that may be associated with decreased renal function after radical nephroureterectomy (RNU). METHODS: This study included 252 patients who underwent laparoscopic RNU with an estimated glomerular filtration rate (eGFR) ≥ 30 ml/min/1.73 m2 in three institutions. We assessed the association between hydronephrosis grade and perioperative renal function and performed a stepwise multivariate linear regression analysis to identify factors associated with postoperative eGFR. Patients with preoperative eGFR ≥ 50 ml/min/1.73 m2 were divided into a training set and an independent external validation set to develop a predictive model for postoperative renal function. RESULTS: The median preoperative and postoperative eGFR were 61.1 and 46.4 ml/min/1.73 m2, respectively. The eGFR preservation rates were 66.9%, 66.6%, 88.1%, and 100.0% in groups without, with mild, moderate, and severe hydronephrosis, respectively, and this difference was statistically significant (p < 0.001). Multivariate analysis revealed that factors predictive of postoperative eGFR included sex, preoperative eGFR, clinical T stage (cT3-4), and the presence of moderate or severe hydronephrosis. Our predictive model, based on these factors, positively correlated with actual postoperative renal function, and the similarity in categories with or without renal function insufficiency between predicted and actual postoperative renal functions was 78% in both training and validation sets. CONCLUSION: Moderate or severe hydronephrosis is associated with a modest postoperative decline in renal function, while mild hydronephrosis is not. Our predictive model may be useful in predicting postoperative renal function insufficiency and guiding decision-making for perioperative medical treatment.

Clinical outcomes following laparoscopic radical nephroureterectomy in octogenarians.

BACKGROUND: This study aimed to compare the incidence of postoperative complications occurring within 30 days of surgery between octogenarians and younger patients and identify preoperative risk factors for the incidence of postoperative complications. Moreover, we also compared the oncological outcomes between octogenarians and younger patients. METHODS: This retrospective study included 283 patients who underwent laparoscopic radical nephroureterectomy for upper tract urothelial carcinoma from 2002 to 2020. The patients were divided into octogenarians and younger patients (age: < 80 years), and their clinical characteristics, perioperative parameters, and postoperative complications were evaluated. The predictors of postoperative complications were evaluated using logistic regression models. Recurrence-free survival, cancer-specific survival, and overall survival were measured using the Kaplan-Meier method. RESULTS: Twelve (17.1%) octogenarians and 40 (18.7%) younger patients had postoperative complications. No significant difference in the incidence of postoperative complications was observed between octogenarians and younger patients (p = 0.14). A high body mass index was a significant risk factor for complications (p = 0.03). The 5-year recurrence-free survival, cancer-specific survival, and overall survival rates for octogenarians and younger patients were 72% and 64% (p = 0.31), 76% and 63% (p = 0.63), and 43% and 63% (p = 0.06), respectively. CONCLUSION: Laparoscopic radical nephroureterectomy can be performed in octogenarians with complication rates similar to those in younger patients. Similarly, the outcomes of laparoscopic radical nephroureterectomy for oncological control do not differ significantly between octogenarians and younger patients. This procedure is safe and effective for selected octogenarians.

Safety and efficacy of ureteroscopy for urolithiasis in octogenarians.

OBJECTIVE: To examine the safety and efficacy of ureteroscopy (URS) for urolithiasis in octogenarians, and identify preoperative risk factors for the incidence of postoperative complications. METHODS: The patients who underwent URS for urolithiasis were divided into octogenarians and younger patients (age: <80 years), and the groups were compared regarding their clinical characteristics, intraoperative and postoperative complications, and stone-free rate. The predictors of postoperative complications were evaluated using logistic regression models. RESULTS: A total of 1207 patients were included, 166 in the octogenarian patient group and 1041 in the younger patient group. The proportion of female patients (p < 0.001), American Society of Anesthesiologists (ASA) score (p < 0.001), rate of preoperative pyelonephritis (p < 0.001), and diabetes mellitus (p = 0.003) were higher in the octogenarian group. No statistically significant differences were found between the two groups regarding stone size, location, and intraoperative complications. Postoperative complications, which reached a significant difference, were observed in 34 (20.5%) octogenarians and 117 (11.2%) younger patients (p = 0.002). However, age itself was not significantly associated with postoperative fever, the most frequent postoperative complication, in multivariate analysis. Female sex, ASA score of ≥3, history of diabetes mellitus, and prolonged operative time (≥120 min) were the significant predictors of fever. The stone-free rate in the octogenarian group was superior to that in the younger patient group (80.1% vs. 70.6%, respectively; p = 0.035). CONCLUSION: Our results suggest that URS for urolithiasis can be safely and effectively applied to octogenarians in selected cases.

Preoperative risk classification for intravesical recurrence after laparoscopic radical nephroureterectomy for upper tract urothelial carcinoma in a multi-institutional cohort.

INTRODUCTION: This study aimed to identify preoperative risk factors and create a risk classification for intravesical recurrence of upper urinary tract urothelial carcinoma only after laparoscopic radical nephroureterectomy in a multi-institutional cohort. METHODS: We retrospectively analyzed 283 patients who had undergone laparoscopic radical nephroureterectomy for nonmetastatic upper tract urothelial cancer between March 2002 and March 2020. The cumulative incidence of intravesical recurrence for 224 patients without previous or concomitant bladder cancer was examined using multivariate Fine-Gray competing risks proportional hazards models. A risk stratification model was created to predict subsequent patient outcomes based on the results. RESULTS: The median follow-up duration was 33.3 months, and 71 (31.7%) patients experienced intravesical recurrence. The estimated cumulative incidence of intravesical recurrence at one and 5 years was 23.5% and 36.4%, respectively. In multivariate analysis, the presence of ureter tumors and multiple tumors were shown to be independently significant predictive factors for intravesical recurrence. Based on the results, we classified patients into three risk groups. The cumulative incidence rates of intravesical recurrence within 5 years after surgery were 24.4%, 42.5%, and 66.7% in the low-, intermediate-, and high-risk groups, respectively. CONCLUSIONS: We identified risk factors and created a risk classification model for intravesical recurrence of upper urinary tract urothelial carcinoma only after laparoscopic radical nephroureterectomy. Based on this model, an individualized surveillance protocol or adjuvant therapy could be provided.

Complications and their management following retroperitoneal lymph node dissection in conjunction with retroperitoneal laparoscopic radical nephroureterectomy.

OBJECTIVES: To describe the detailed perioperative complications and their management after retroperitoneal lymph node dissection with retroperitoneal laparoscopic radical nephroureterectomy for patients with upper tract urothelial carcinoma at three institutions. METHODS: Retroperitoneal lymph node dissection was performed on patients with upper tract urothelial carcinoma located at the pelvis and/or upper or middle ureter, and its template included the renal hilar and para-aortic lymph nodes (left side) and the renal hilar, paracaval, retrocaval, and intra-aortocaval lymph nodes (right side). The lymph nodes and kidneys were removed en bloc. The primary endpoint was postoperative complication rates, and the secondary endpoints were intraoperative findings and chylous leakage management. The associations of retroperitoneal lymph node dissection with postoperative complications were examined using logistic regression with propensity score techniques. RESULTS: Eighty-eight (31%) and 195 (69%) patients underwent and did not undergo retroperitoneal lymph node dissection, respectively. There was no significant difference in postoperative complications and other perioperative findings in the entire cohort, except for prolonged operation time. Retroperitoneal lymph node dissection was not statistically significantly associated with total and serious complications in propensity score analyses. Postoperative chylous leakage could be conservatively managed even though it is common in patients with retroperitoneal lymph node dissection (14/88 (16%)). The incidence of chylous leakage was significantly lower in patients whose lymphatic vessels were meticulously clipped completely during retroperitoneal lymph node dissection (5.3% vs 24%; P = 0.017). CONCLUSION: There was no association between retroperitoneal lymph node dissection with laparoscopic radical nephroureterectomy and postoperative complications. However, chylous leakage is often observed after retroperitoneal lymph node dissection and careful management is highly required. The use of clips during retroperitoneal lymph node dissection is recommended to minimize chylous leakage risk.

Pregnancy and Lactation-Associated Osteoporosis Successfully Treated with Romosozumab: A Case Report.

Pregnancy- and lactation-associated osteoporosis (PLO) is a rare type of premenopausal osteoporosis that occurs mainly in the third trimester or immediately after delivery; one of its most common symptoms is back pain caused by a vertebral fracture. The pathogenesis of PLO is unclear, and there is no accepted consensus regarding the treatment of PLO. Although treatments with drugs such as bisphosphonate, strontium ranelate, denosumab, and teriparatide were reported, there is no report of a patient with PLO treated with romosozumab. We present the first case of a patient with PLO treated with romosozumab following 4-month teriparatide treatment. A 34-year-old primiparous and breastfeeding Japanese woman experienced severe low back pain 1 month postdelivery. She was diagnosed with PLO on the basis of low bone marrow density (BMD) and multiple vertebral fractures with no identified cause of secondary osteoporosis. She was treated with teriparatide injection for 4 months, but the treatment was discontinued because of the patient feeling severe nausea after every teriparatide injection and the appearance of new vertebral fractures. Thereafter, we used romosozumab for 12 months. After the romosozumab treatment, her BMD was increased from the baseline by 23.6% at L1-L4, 6.2% at the femoral neck, and 11.2% at the total hip. Treating PLO with 12-month romosozumab after 4 months of teriparatide injection remarkably increased the BMD of the lumbar spine, femoral neck, and total hip without subsequent fracture. Romosozumab has potential as a therapeutic option to improve the BMD and reduce the subsequent fracture risk of patients with PLO.

[Renal Subcapsular Hematoma after Transurethral Ureterolithotripsy].

Subcapsular renal hematoma is a complication of extracorporeal shock wave lithotripsy or percutaneous nephrolithotripsy. Although it can occur after transurethral ureterolithotripsy (TUL), there is no consensus on the risk factors, outcomes, and its management. This study aimed to elucidate the clinical courses of patients with subcapsular hematoma after TUL. We retrospectively investigated 1,235 patients who underwent TUL from October 2011 to December 2020 at our hospital and identified cases with subcapsular hematoma diagnosed after surgery. Subcapsular hematoma was diagnosed in 5 of the 1,235 (0.40%) patients, whose median age was 63 (49-69) years. The median operation time, hematoma diameter, and hemoglobin decrease were 66 (35-115) min, 8.2 (5.4-10.5) cm, and 1.6 (0.7-2.6) g/dl, respectively. All patients were conservatively managed without invasive interventions (eg, embolization), although one patient required blood transfusion. In conclusion, this study presented five cases with renal subcapsular hematoma after TUL that could be conservatively managed. It is important not to miss the timing of therapeutic intervention while observing the progress after diagnosis.

[Risk Factors for Febrile Urinary Tract Infection after Transurethral Ureterolithotripsy : ANALYSIS of Treatment Outcomes of 1,235 Patients at a Single Center].

Recently, ureteroscopic lithotripsy remains the standard treatment for urolithiasis, with postoperative febrile upper urinary tract infection (fUTI) being one of its most significant complications. The current study sought to investigate the treatment outcomes of ureterorenoscopy (URS), morbidity and risk factors of postoperative fUTI at our hospital. A total of 1,235 patients who underwent URS (including those who underwent only semi-rigid URS) for upper urinary tract stones at our hospital between October 2011 and December 2019 were retrospectively analyzed. Patients had a median age of 63 years and a median stone length of 11.4 mm. F-URS was performed in 1,188 cases (96.2%) among whom 92.1% were stone-free or had stones that fractured into dust. Postoperative fUTI and sepsis occurred in 127 (10.3%) and 18 (1.5%) patients, respectively. Multivariate analysis identified female sex, American Society of Anesthesiologists (ASA) score ≥ 3, calculus length ≥ 20 mm, history of diabetes mellitus, and history of obstructive pyelonephritis as risk factors for postoperative fUTI. The scoring system (range 0-4) were positively correlated with the postoperative fUTI rate (score 0 : 3.1%, 1 : 12.4%, 2 : 14.1%, 3 : 23.7%, 4 : 40%). A significant difference in the rates was noted between those with a score of 0 (low-risk group), 1-2 (intermediate-risk group), and 3-4 scores (high-risk group). In conclusion, the overall incidence of postoperative fUTI was 10.3%, which was associated with sex, poor ASA scores, stone size, presence of diabetes mellitus, and history of pyelonephritis. The scoring system created using these factors can be useful in predicting postoperative fUTI.

Effect of optimal neoadjuvant chemotherapy on oncological outcomes of locally advanced bladder cancer with laparoscopic radical cystectomy: A matched-pair analysis in a multicenter cohort.

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.

[Efficacy and Safety of Retrograde Ureterorenoscopic Lithotripsy for Patients with Renal or Ureteral Anatomic Abnormalities or Urinary Diversion].

Retrograde ureterorenoscopic lithotripsy is one of the first-line therapies for urolithiasis. In some cases, however, thisapproach may be difficult to adopt because of factorss uch asrenal/ureteral anatomic abnormalities or urinary diversion. This study aims to investigate the safety and efficacy of retrograde ureterorenoscopic lithotripsy in patients with the above-mentioned conditions. We retrospectively investigated all such patients who underwent retrograde ureterorenoscopic lithotripsy from May 2009 to December 2019 at our hospital. "Stone free"was defined as the total absence of residual fragments, and "success"wasdefined asthe absence of hydronephrosisand residual fragmentsgreater than 4 mm at the end of 4 weeks. Complications were classified according to the modified Clavien-Dindo classification system. Twenty-one procedureswere performed in 19 patientswhos e conditionswere horseshoe kidney, ureteral duplex, cross-fused renal ectopia, cutaneous ureterostomy, ileal conduit, ureterocystoneostomy, and cystostomy. The median age was 67 (40-93) years, the median stone diameter was 9.6 (5.0-16.0) mm, the median operation time was 63 (12-158) minutes, and the complete stone-free rate and success rate were 42.9 and 71.4%, respectively. The complication rate was 19.0% ; however, no serious complications were observed. In conclusion, retrograde ureterorenoscopic lithotripsy is an effective and safe procedure for patientss uffering from urolithiasis with renal/ureteral anatomic abnormalitiesor previousurinary diversion.

[Two Cases of Renal Pelvic Rupture Due to Trauma in a Patient with Ureteropelvic Junction Stenosis].

A pathologic kidney with hydronephrosis is prone to rupture after minor trauma to the renal pelvis ; however, it is controversial whether drainage, such as nephrostomy and ureteral stenting, should be performed in this setting. Herein we report traumatic rupture of the renal pelvis in 2 patients with ureteropelvic junction stenosis at two centers. Case 1 : A 15-year-old boy sustained a blunt injury on his left back while playing football. His family physician referred the patient to our hospital for suspected left renal injury. Contrast-enhanced abdominal computed tomography showed left hydronephrosis and fluid accumulation in the left retroperitoneal space, which led to a diagnosis of rupture of the left renal pelvis. The patient was treated conservatively ; however, fluid accumulation around the kidney worsened. A ureteral stent was placed, and the patient's renal colic and imaging findings improved. Case 2 : A 13-yearold boy fell and bruised his abdomen while playing soccer. He was unable to walk because of pain, and was brought to our hospital by ambulance. Contrast-enhanced abdominal computed tomography showed left hydronephrosis and fluid accumulation in the left retroperitoneal space, which led to a diagnosis of rupture of the left renal pelvis. A ureteral stent was placed on the same day, and the patient's renal colic improved.

Preoperative hydronephrosis as a predictor of postnephroureterectomy survival in patients with upper tract urothelial carcinoma: a two-center study in Japan.

OBJECTIVE: To evaluate the predictive value of preoperative hydronephrosis for pathological outcome and prognosis in patients with upper tract urothelial carcinoma treated with nephroureterectomy. METHODS: 167 patients with UTUC treated with nephroureterectomy at our two institutions in Japan between 2002 and 2017 were retrospectively analyzed. Preoperative computed tomography scans were evaluated for the presence of ipsilateral hydronephrosis. Preoperative hydronephrosis's associations with pathological outcome and postnephroureterectomy survival were assessed. RESULTS: Ipsilateral hydronephrosis was present in 102 patients (61.1%). Preoperative hydronephrosis was not associated with higher pathological T stage (T3 or greater). Patients with preoperative hydronephrosis compared with patients without preoperative hydronephrosis had significantly worse recurrence-free survival (RFS) (5-year survival, 61.9% and 77.6%, respectively; p = 0.033), disease-specific survival (DSS) (5-year survival, 66.9% and 88.1%, respectively; p = 0.026), and overall survival (OS) (5-year survival, 54.5% and 80.6%, respectively; p = 0.030). A multivariate Cox regression model identified preoperative hydronephrosis and higher clinical T stage (T3 or greater) as an independent predictor of shorter RFS (p = 0.015 and 0.0009, respectively). We segregated the patients into three risk groups based on the number of these two prognostic factors: 0, favorable risk; 1, intermediate risk; 2, poor risk. The favorable-risk group had significantly better RFS (p = 0.0003), DFS (p = 0.0001), and OS (p = 0.0007) than the poor and intermediate-risk groups (RFS (p = 0.0011), DFS (p = 0.0017), and OS (p = 0.0043)). CONCLUSION: The presence of preoperative hydronephrosis was a significant risk factor affecting survival. Our risk classification based on preoperative hydronephrosis and clinical T stage may be helpful for patient counselling and decision-making before nephroureterectomy.

Oncological outcomes and recurrence patterns after laparoscopic radical cystectomy for bladder cancer: A Japanese multicenter cohort.

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.

Perioperative and oncological outcomes of laparoscopic radical cystectomy with intracorporeal versus extracorporeal ileal conduit: A matched-pair comparison in a multicenter cohort in Japan.

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.

[A Case of atypical Femoral Fracture after Dosing Denosumab].

For the management of patients with castration-resistant prostate cancer with bone metastases, bisphosphonates and denosumab are used to prevent skeletal related events. Osteonecrosis of the jaw and hypocalcemia have been reported in patients treated with denosumab, but there have been few reports of atypical femoral fracture (AFF). Here, we report a case of AFF after dosing denosumab. A 69-year-old man with prostate-specific antigen (PSA) level of 13.08 ng/ml was diagnosed with adenocarcinoma of the prostate, cT3a, N0, M1b, with Gleason score of 4+4=8 and bone metastases to pubis and ischium. Combined-androgen blockade therapy and denosumab were initiated in April 2014. Forty-eight months later, he had left knee pain. He had a magnetic resonance imaging of his left knee, but it showed no obvious findings. However, he had pain in the bilateral thighs and visited the department of orthopedics at our hospital. Pelvic X-ray showed thickening of the bone cortex at the lateral boarders of bilateral femur, and femoral CT showed faint fracture line in bilateral femur. He was diagnosed with AFF, and denosumab was discontinued. Ourcase suggests that we must considerthe possibility of AFF when pain around the thigh occurs after dosing denosumab.

Mathematical modeling of septic shock based on clinical data.

BACKGROUND: Mathematical models of diseases may provide a unified approach for establishing effective treatment strategies based on fundamental pathophysiology. However, models that are useful for clinical practice must overcome the massive complexity of human physiology and the diversity of patients' environmental conditions. With the aim of modeling a complex disease, we choose sepsis, which is highly complex, life-threatening systemic disease with high mortality. In particular, we focused on septic shock, a subset of sepsis in which underlying circulatory and cellular/metabolic abnormalities are profound enough to substantially increase mortality. Our model includes cardiovascular, immune, nervous system models and a pharmacological model as submodels and integrates them to create a sepsis model based on pathological facts. RESULTS: Model validation was done in two steps. First, we established a model for a standard patient in order to confirm the validity of our approach in general aspects. For this, we checked the correspondence between the severity of infection defined in terms of pathogen growth rate and the ease of recovery defined in terms of the intensity of treatment required for recovery. The simulations for a standard patient showed good correspondence. We then applied the same simulations to a patient with heart failure as an underlying disease. The model showed that spontaneous recovery would not occur without treatment, even for a very mild infection. This is consistent with clinical experience. We next validated the model using clinical data of three sepsis patients. The model parameters were tuned for these patients based on the model for the standard patient used in the first part of the validation. In these cases, the simulations agreed well with clinical data. In fact, only a handful parameters need to be tuned for the simulations to match with the data. CONCLUSIONS: We have constructed a model of septic shock and have shown that it can reproduce well the time courses of treatment and disease progression. Tuning of model parameters for each patient could be easily done. This study demonstrates the feasibility of disease models, suggesting the possibility of clinical use in the prediction of disease progression, decisions on the timing of drug dosages, and the estimation of time of infection.

Laparoscopic radical cystectomy in octogenarians: analysis of a Japanese multicenter cohort.

BACKGROUNDS: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Complications and reoperations after laparoscopic radical cystectomy in a Japanese multicenter cohort.

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.

Various checkpoint molecules, and tumor-infiltrating lymphocytes in common pediatric solid tumors: Possibilities for novel immunotherapy.

Long-term survival rates for pediatric patients with cancer have significantly improved, but novel approaches are desired for those with refractory/relapsed solid tumors. Recently, programed cell death-1/programed cell death-ligand-1 blockade has emerged as an effective option for many intractable cancers. However, not all patients show objective response to such therapy. On the other hand, several other checkpoint pathways, including Herpes virus entry mediator (HVEM)/B- and T-lymphocyte attenuator (BTLA), galectin-9 (GAL9)/T-cell immunoglobulin and mucin domain-3 (TIM3), and major histocompatibility complex class II (MHC-II)/lymphocyte activation gene-3 (LAG3), also regulate immune responses in the tumor microenvironment and may be alternative targets for novel immune therapies. In this study, we examined 65 common pediatric solid tumors and characterized the expression of Herpes virus entry mediator, GAL9, and MHC-II on tumor cells and their corresponding receptors B- and T-lymphocyte attenuator, TIM3, and LAG3, respectively, on tumor-infiltrating lymphocytes (TILs) with immunohistochemistry. Whereas the expression of GAL9 and MHC-II was limited, 73% of rhabdomyosarcomas and 100% of osteosarcomas expressed moderate to high levels of Herpes virus entry mediator on the tumor. TILs were detected in all tumor samples except one osteosarcoma. Interestingly, 45% of rhabdomyosarcomas, and 45% of osteosarcomas expressed moderate to high levels of both Herpes virus entry mediator on the tumor cells and B- and T-lymphocyte attenuator on the TILs. Results showed that a subset of pediatric solid tumors expressed tumor-associated checkpoint molecules, and TILs expressed corresponding receptors for these checkpoint molecules. Thus, immunogenic environments may be created, and checkpoint blockade may induce favorable immune responses.