Prognostication in Japanese patients with bacillus Calmette-Guérin-unresponsive non-muscle-invasive bladder cancer undergoing early radical cystectomy.

OBJECTIVES: The US Food and Drug Administration recently defined the clinical term "bacillus Calmette-Guérin-unresponsive non-muscle-invasive bladder cancer" as a disease state resistant to adequate bacillus Calmette-Guérin therapy. There is a significant lack of prognostication for this disease even in patients who have undergone early radical cystectomy. This study aimed to identify the clinical outcomes and prognostic factors in Japanese patients with bacillus Calmette-Guérin-unresponsive non-muscle-invasive bladder cancer who underwent early radical cystectomy. METHODS: Data from a large-scale multicenter retrospective study included 2879 patients with highest-risk or high-risk non-muscle-invasive bladder cancer who received intravesical bacillus Calmette-Guérin induction therapy between January 2000 and December 2019. A total of 141 patients (4.3%) met the criteria for bacillus Calmette-Guérin-unresponsive disease, of whom 47 (33.3%) underwent early radical cystectomy. Prognostic factors for three clinical endpoints, namely, unresectable lesion-free survival, cancer-specific survival, and overall survival, were identified. RESULTS: The highest-risk status at induction bacillus Calmette-Guérin was associated with short unresectable lesion-free survival (hazard ratio 7.85; P < 0.05), cancer-specific survival (hazard ratio 12.24; P < 0.05), and overall survival (hazard ratio 9.25; P < 0.01). Moreover, extravesical tumors (pathological T3 or T4) on the radical cystectomy specimens were associated with poor prognosis and were found at a higher rate in patients with the highest-risk status at induction bacillus Calmette-Guérin than in those with high-risk status (35.7% vs 21.2%). CONCLUSIONS: The highest-risk status among the pre-bacillus Calmette-Guérin factors was associated with upstaging to extravesical tumors and poor prognosis despite early radical cystectomy procedures. Appropriate decision-making and the correct timing of radical cystectomy are vital to avoid treatment delays and improve outcomes.

[Management of Internal Ureteral Stent (Double J-Stent) Occlusion].

Occlusion of internal ureteral stents commonly called double-J (DJ) stent leads to renal dysfunction, urinary tract infection, and difficulty in replacing the stent. We investigated the cause of stent occlusion and whether DJ stent occlusion persisted with change in the type of stent. The internal ureteral stent, Bird® Inlay™ Optima or Boston Scientific® Tria™, was inserted in 43 ureters of 33 patients who underwent replacement more than three times between September 2017 and June 2020. We defined stent occlusion as follows: a guide wire could not be passed through a stent during the replacement. In the first occlusion, the type of stent was changed. In the second occlusion, the stent placement interval was shortened from 12-13 weeks to 6-8 weeks. The presence of urinary stone and insertion of a urethral catheter had a high risk of DJ stent occlusion. Stent occlusion was observed in 20 of the 43 ureters. After the type of stent in 20 ureters with stent occlusion was changed, there were no DJ stent occlusions in 16 of the 20 ureters. Nevertheless, in 4 of the 20 ureters, even if we changed the type, DJ stent occlusion was still present; hence, the replacement interval was shortened. Therefore, changing the type of stent may be a recommended intervention for DJ stent occlusion.

Non-maintenance intravesical Bacillus Calmette-Guérin induction therapy with eight doses in patients with high- or highest-risk non-muscle invasive bladder cancer: a retrospective non-randomized comparative study.

BACKGROUND: To explore possible solutions to overcome chronic Bacillus Calmette-Guérin (BCG) shortage affecting seriously the management of non-muscle invasive bladder cancer (NMIBC) in Europe and throughout the world, we investigated whether non-maintenance eight-dose induction BCG (iBCG) was comparable to six-dose iBCG plus maintenance BCG (mBCG). METHODS: This observational study evaluated 2669 patients with high- or highest-risk NMIBC who treated with iBCG with or without mBCG during 2000-2019. The patients were classified into five groups according to treatment pattern: 874 (33%) received non-maintenance six-dose iBCG (Group A), 405 (15%) received six-dose iBCG plus mBCG (Group B), 1189 (44%) received non-maintenance seven-/eight-dose iBCG (Group C), 60 (2.2%) received seven-/eight-dose iBCG plus mBCG, and 141 (5.3%) received only ≤5-dose iBCG. Recurrence-free survival (RFS), progression-free survival, and cancer-specific survival were estimated and compared using Kaplan-Meier analysis and the log-rank test, respectively. Propensity score-based one-to-one matching was performed using a multivariable logistic regression model based on covariates to obtain balanced groups. To eliminate possible immortal bias, 6-, 12-, 18-, and 24-month conditional landmark analyses of RFS were performed. RESULTS: RFS comparison confirmed that mBCG yielded significant benefit following six-dose iBCG (Group B) in recurrence risk reduction compared to iBCG alone (groups A and C) before (P < 0.001 and P = 0.0016, respectively) and after propensity score matching (P = 0.001 and P = 0.0074, respectively). Propensity score-matched sequential landmark analyses revealed no significant differences between groups B and C at 12, 18, and 24 months, whereas landmark analyses at 6 and 12 months showed a benefit of mBCG following six-dose iBCG compared to non-maintenance six-dose iBCG (P = 0.0055 and P = 0.032, respectively). There were no significant differences in the risks of progression and cancer-specific death in all comparisons of the matched cohorts. CONCLUSIONS: Although non-maintenance eight-dose iBCG was inferior to six-dose iBCG plus mBCG, the former might be an alternative remedy in the BCG shortage era. To overcome this challenge, further investigation is warranted to confirm the real clinical value of non-maintenance eight-dose iBCG.

Periprostatic fat thickness quantified by preoperative magnetic resonance imaging is an independent risk factor for upstaging from cT1/2 to pT3 in robot-assisted radical prostatectomy.

OBJECTIVES: To analyze the correlation between periprostatic fat thickness on multiparametric magnetic resonance imaging and upstaging from cT1/2 to pT3 in robot-assisted radical prostatectomy. METHODS: We retrospectively evaluated data from men with cT1/2 prostate cancer treated with robot-assisted radical prostatectomy at Nara Prefecture General Medical Center, Nara, Japan, between March 2013 and December 2017. We calculated the periprostatic fat thickness and subcutaneous thickness from preoperative multiparametric magnetic resonance imaging. We divided the cohort into two groups for analysis. Group 1 included patients upstaged from clinical to pathological stage, whereas group 2 included those without upstaging. RESULTS: Data on 220 patients meeting the inclusion criteria were included in the analysis. A total of 36 patients were upstaged from clinical T1 or T2 to pathological T3, whereas 184 patients were not upstaged. The upstaging was associated with prostate volume, Gleason score, prostate-specific antigen density, periprostatic fat thickness, Prostate Imaging Reporting and Data System score based on univariate analysis. Multivariate analysis showed prostate volume (P = 0.03, odds ratio 0.958, 95% confidence interval 0.921-0.996), Gleason score (P = 0.022, odds ratio 2.676, 95% confidence interval 1.153-6.213) and periprostatic fat thickness (P = 0.004, odds ratio 1.26, 95% confidence interval 1.079-1.471) as independent risk factors of upstaging. CONCLUSIONS: Prostate volume, Gleason score and periprostatic fat thickness on multiparametric magnetic resonance imaging are significantly associated with and independent risk factors for upstaging from cT1/2 to pT3 in patients undergoing robot-assisted radical prostatectomy.

The diagnostic utility of retroperitoneoscopic tissue biopsy for unresectable retroperitoneal lesions excluding urogenital cancers.

BACKGROUND: Retroperitoneal tumors are an uncommon disease known to consist of a diverse group of benign and malignant neoplasms. Treatment of unresectable retroperitoneal lesions requires pathological diagnosis. Here, we report the utility and safety of retroperitoneoscopic biopsy for unresectable retroperitoneal lesions excluding urogenital cancers. METHODS: We analyzed 47 patients consisting of 23 (49%) and 24 (51%) cases that underwent retroperitoneoscopic tissue biopsy and open biopsy, respectively. The clinicopathological features, including postoperative complications, were compared between the two groups. RESULTS: Tumor pathology was diagnosed successfully with a single operation in all patients. Malignant pathology (68%) was more common than benign pathology (32%). The most common pathology was malignant lymphoma, which accounted for about 50% of all cases. There was no significant difference with respect to the age, sex, tumor size, presence of tumor-related symptom, histopathology, operative time, and complications. Three (13%) of 23 patients in the retroperitoneoscopic biopsy group received percutaneous needle biopsy before laparoscopic excisional biopsy because the evaluation of needle cores failed to confirm subclasses of diagnosed pathologies. One patient was converted to open surgery just after the initiation of operation due to severe adhesion of adjacent structures. We had two cases with iatrogenic urinoma due to ureteral injury after retroperitoneoscopic biopsy. CONCLUSIONS: We conclude that retroperitoneoscopic biopsy is a safe and useful tool for benign and malignant retroperitoneal lesions, in comparison to open biopsy. It is critical to carefully examine the preoperative imaging for the location of tumors, especially those close to the renal pelvis and ureter.

[Pubic Bone Osteomyelitis in Patient with Prostate Cancer after Robot-Assisted Laparoscopic Prostatectomy; A Case Report].

A 72-old man had undergone robot-assisted laparoscopic prostatectomy for localized prostate cancer (cT2aN0M0). He was referred to us with a complaint of lower abdominal pain, pain at the bilateral inner thigh, gait disturbance and persistent pyuria three months after surgery. A pelvic MRI revealed inflammation of the pubic area, and pubic bone osteomyelitis was suspected. He was admitted and administered doripenem hydrate (DRPM) intravenously for 3 weeks. The symnptoms of gait disturbance, pain at the bilateral inner thigh, and lower abdominal pain were improved gradually. Levofloxacin hydrate (LVFX）wa s administered orally for 8 weeks subsequently. He has been followed and has had no recurrence of these symptoms.

[Migration of Hem-o-Lok Clips into the Urinary Bladder Used during Robot-Assisted Laparoscopic Prostatectomy].

Recently, robot-assisted laparoscopic prostatectomy (RALP) has become a widely accepted surgical alternative for the treatment of prostate cancer. The intravesical migration of clips is a rare surgical complication of RALP. From March2013 to July 2018, 320 patients underwent RALP at our hospital. Migration of a Hem-o-Lok clip into the urinary bladder occurred in 4 of the 320 patients (1.3%). We analyzed these 4 patients in terms of subjective symptoms, intra- and post-operative findings, site of the migrated clip, and its treatment. The mean duration from RALP to the diagnosis was 13.8 months (2-26 months). The main symptoms due to migrated clips were : narrowed urinary stream, perineal pain, gross hematuria, and painful urination. In all cases, the size of the migrated clip was medium-large, and the events developed on the side contralateral to the first assistant. The clips were transurethrally removed using a Holmium-laser in 2 patients, and spontaneous excretion was observed in 1. The remaining patient has been asymptomatic and is being conservatively observed. In order to prevent the migration of clips used during RALP, the size of the clips and direction of the clip tail may be important. The first assistant should place the clips carefully, especially on the contralateral side.

Transfection of T-Box Transcription Factor BRACHYURY and SOX2 Synergistically Promote Self-Renewal and Invasive Phenotype in Oral Cancer Cells.

Recent studies suggest that epithelial⁻mesenchymal transition (EMT) correlates with cancer metastasis. In addition, there is growing evidence of the association of EMT with cancer stem cells (CSCs). Recently, we showed that the T-box transcription factor BRACHYURY could be a strong regulator of EMT and the CSC phenotype, which were effectively suppressed by a BRACHYURY knockdown in an adenoid cystic carcinoma cell line. In this study, we further tested whether BRACHYURY is a regulator of cancer stemness by means of forced expression of BRACHYURY in oral cancer cell lines. BRACHYURY, SOX2, or both were stably transfected into oral carcinoma cell lines. We analysed these transfectants with respect to self-renewal phenotypes using a sphere-formation assay, and we assessed the expression levels of EMT markers and stem cell markers using real-time reverse transcription-polymerase chain reaction (RT-PCR). Cell migration and invasiveness in vitro were evaluated using a wound healing assay and a tumour cell dissemination assay, respectively. Forced expression of BRACHYURY or SOX2 slightly increased expression of EMT and stem cell markers and the self-renewal phenotype. The expression levels, however, were much lower compared to those of cancer stem cell-like cells. Forced co-expression of BRACHYURY and SOX2 strongly upregulated EMT and stem cell markers and the self-renewal phenotype. Cell migration and invasiveness in vitro were also remarkably enhanced. These synergistic effects increased expression levels of FIBRONECTIN, SNAIL, SLUG, ZEB1, and TGF-ß2. In particular, the effects on FIBRONECTIN and TGF-ß2 were significant. We found that BRACHYURY and SOX2 synergistically promote cancer stemness in oral cancer cells. This finding points to the importance of gene or protein networks associated with BRACHYURY and SOX2 in the development and maintenance of the CSC phenotype.

[Iatrogenic Injuries of Urinary Tract : Outcomes of Surgical Repairs].

Iatrogenic urinary tract injuries are known complications of digestive and pelvic surgeries. We retrospectively reviewed 13 patients with bladder injuries and 16 patients with ureteral injuries requiring surgical repair or stent placement in our hospital between 2013 and 2016. Obstetric-gynecologic surgery accounted for 10 bladder injuries and 11 ureteral injuries on hysterectomy and Cesarean section. Digestive surgery led to 1 bladder injury and 5 ureteral injuries on colon resection, and urologic surgery resulted in 1 injury on biopsy of a retroperitoneal tumor. Regarding bladder injuries, 10 patients underwent cystorrhaphy, and 3 patients received indwelling of a transurethral Foley catheter alone. Concerning ureteral injuries, 7 patients underwent repair of the injured ureter (ureteroneocystostomy in 5, and ureteroureterostomy in 2), and 9 patients received ureteral stent placement after postoperative retrograde urography. Repair failure was defined when urine leakage, urinary fistula, or urinary stricture requiring ureteral stent placement still existed at 90 days after the repair treatment. The bladder injuries in all 13 cases were successfully repaired. The ureteral injury treatments in 7 out of 16 patients (43.8%) were judged as being unsuccessful because of the condition requiring a ureteral stent at 90 days. There was a correlation between the delayed diagnosis of ureteral injury and unsuccessful repair. The present study showed that the prompt identification of urinary tract injuries, especially ureteral injuries, can result in decreased morbidity andsubsequently improved outcomes.

[Robot-Assisted Laparoscopic Prostatectomy for Patient with Hereditary Hemorrhagic Telangiectasia: A Case Report].

A 69-year-old man who had a history of several nasal hemorrhages and transfusions presented with hereditary hemorrhagic telangiectasia. He was referred to the previous hospital due to the elevation of prostate specific antigen (PSA) to 17.2 ng/ml, and was diagnosed with prostate cancer (cT3aN0M0, Gleason 4 + 5). He was referred to our hospital for the treatment of prostate cancer. Contrast lung computed tomography and brain magnetic resonance imaging did not show arteriovenous fistula in either the lung or brain. Upper gastrointestinal endoscopy showed capillary dilatations in the gastric mucosa. Robot-assisted laparoscopic prostatectomy with Trendelenburg position under general anesthesia was performed. Tracheal intubation was made using bronchofiberscopy. A gastric tube was not inserted. Intra- and postoperative course was uneventful, and there has been no elevation of PSA during the eight months followed.

[Bladder Rupture during Intravesical BCG Therapy : A Case Report].

A 69-year-old man received transurethral resection (TUR) ofbladder tumor. The histopathological diagnosis was urothelial carcinoma, high grade, pT1＋pTis. The surgical specimens obtained by second TUR showed no residual malignancy histopathologically. Intravesical Bacillus Calmette-Guerin (BCG) instillation therapy was initiated 2 months after the second TUR. He complained of lower abdominal pain and painful urination on the day following the second instillation of BCG. Computed tomography and cystography demonstrated rupture ofthe urinary bladder. During 2 weeks ofconservative treatment, the symptoms persisted. Then, open repair ofthe bladder was performed. Intravesical BCG therapy has been a widely accepted treatment for bladder cancer with high grade Ta and T1, and carcinoma in situ. In the present case, thinning ofthe bladder wall, delayed wound healing caused by 2 TURs, and abdominal pressure may have been the factors leading to the bladder rupture in addition to inflammation of the bladder due to BCG instillation. Although bladder rupture caused by intravesical BCG therapy has not been reported, we must be aware ofthe possibility ofthis rare condition, especially after 2 consecutive TURs.

[Acute Urinary Retention Caused by Acute Disseminated Encephalomyelitis : A Case Report].

An 11-year-old boy was referred to our department with the chief complaint of acute urinary retention. He had had a history of viral enteritis a few days before the onset of dysuria. He presented with a slight fever, mild headache and weakness of the extremities. A cerebrospinal fluid examination showed the elevation of cell number (cell number : 158/3, polynuclear cells : 29/3, and mononuclear cells : 129/3). Although spinal magnetic resonance imaging (MRI) did not show abnormal findings, fluid attenuated inversion recovery (FLAIR) image of the brain MRI showed a high signal area on the cerebral cortex. Acute disseminated encephalomyelitis (ADEM) was suspected from the clinical course, the cerebrospinal fluid examination, and brain MRI findings. A urethral catheter was indwelled for urinary retention, and steroid pulse therapy was promptly started. After removal of the urethral catheter seven days after the therapy initiation, normal urination without residual urine was observed. Findings of a cerebrospinal fluid test and brain MRI also showed improvement.

[Ureteral Cancer Developing in Retrocaval Ureter : A Case Report].

Ureteral cancer in the retrocaval ureter is rare. We herein report a patient with this condition laparoscopically treated. A 69-year-old man was referred to us because of right ureteral cancer diagnosed during ureteroscopic surgery for a ureteral calculus. Histological diagnosis of the ureteroscopically biopsied material was non-invasive papillary urothelial carcinoma, low grade (G2). Computed tomography (CT) demonstrated a retrocaval ureter : a double J stent placed during ureteroscopy assisted the diagnosis. The patient underwent retroperitoneoscopic complete nephroureterectomy on the right side. Sufficient separation of the right ureter and the inferior vena cava under retroperitoneoscopic procedures facilitated en bloc extirpation of the kidney and ureter with a minimal lower abdominal incision. The surgical procedures for ureteral cancer in the retrocaval ureter, should be preoperatively considered with care.

[Laparoscopic Non-Ischemic Partial Nephrectomy Using a Microwave Tissue Coagulator : A Single-Institutional Study].

We retrospectively investigated the surgical outcomes of renal cell carcinoma (RCC), perioperative complications, and residual renal function in patients receiving laparoscopic non-ischemic partial nephrectomy using a microwave tissue coagulator (MTC). Between January 2002 and December 2015, laparoscopic non-ischemic partial nephrectomy using MTC was performed in 49 patients. The histological diagnosis was RCC in 38 patients, angiomyolipoma in 4, oncocytoma in 2, and others in 5. A histologicallyproven positive surgical margin was observed in 1 (2.0%). Postoperative urine leakage occurred in 1, and it was treated conservatively. The mean follow-up period was 32.0 months. Although there was no patient who died of RCC, local recurrence occurred in 2 patients (4.1%) during the follow-up period. One of these 2 patients had a positive surgical margin. Deterioration of the residual renal function was not observed. Laparoscopic non-ischemic partial nephrectomy using MTC was safe and useful in terms of cancer control and preservation of renal function.

Subsequent Upper Urinary Tract Carcinoma Related to Worse Survival in Patients Treated with BCG.

Upper urinary tract urothelial carcinoma (UTUC) after intravesical bacillus Calmette-Guerin (BCG) therapy is rare, and its incidence, clinical impact, and risk factors are not fully understood. To elucidate the clinical implications of UTUC after intravesical BCG therapy, this retrospective cohort study used data collected between January 2000 and December 2019. A total of 3226 patients diagnosed with non-muscle-invasive bladder cancer (NMIBC) and treated with intravesical BCG therapy were enrolled (JUOG-UC 1901). UTUC impact was evaluated by comparing intravesical recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) rates. The predictors of UTUC after BCG treatment were assessed. Of these patients, 2873 with a medical history that checked UTUC were analyzed. UTUC was detected in 175 patients (6.1%) during the follow-up period. Patients with UTUC had worse survival rates than those without UTUC. Multivariate analyses revealed that tumor multiplicity (odds ratio [OR], 1.681; 95% confidence interval [CI], 1.005-2.812; p = 0.048), Connaught strain (OR, 2.211; 95% CI, 1.380-3.543; p = 0.001), and intravesical recurrence (OR, 5.097; 95% CI, 3.225-8.056; p < 0.001) were associated with UTUC after BCG therapy. In conclusion, patients with subsequent UTUC had worse RFS, CSS, and OS than those without UTUC. Multiple bladder tumors, treatment for Connaught strain, and intravesical recurrence after BCG therapy may be predictive factors for subsequent UTUC diagnosis.

Severe subcutaneous emphysema caused by small injury to the abdominal wall during robot-assisted laparoscopic radical prostatectomy.

A 67-year-old man underwent RARP in the Trendelenburg position with pneumoperitoneum at 12 mmHg. Gradual elevation of End-tidal CO2(EtCO2) began, and extensive subcutaneous emphysema was recognized when EtCO2 reached 58 mmHg. After interruption of pneumoperitoneum, careful observation of the surgical field led to detect an injury of the abdominal wall of 1 cm in length, suggesting the cause of severe subcutaneous emphysema. The injury was repaired and RARP was terminated without any cardiovascular problems. Attention should be paid that even minor abdominal wall injury could lead to severe subcutaneous emphysema which may cause respiratory or cardiovascular problems during laparoscopic surgeries.

[IMPACT OF THE SPREAD OF COVID-19 ON THE UROLOGY PRACTICE IN OUR HOSPITAL].

(Purpose) Our hospital plays the role of a prefectural core hospital for COVID-19 and mainly accepts moderate and severely ill patients. In addition, our hospital is also actively responsible for regional emergency medical care, and is designated as a cancer treatment cooperation base hospital. We started accepting patients with COVID-19 in April 2020, and 2 out of 10 wards of our hospital are in operation as exclusive wards for COVID-19 at the time of May 31, 2021. In this study, we compared the effects of the spread of COVID-19 on our urological practice with those before the spread. (Materials and methods) The number of urological operations, their types and average length of stay, the number of outpatients / inpatients, the unit cost of medical treatment income, the referral rate, and the reverse referral rate were calculated based on the in-hospital clinical statistics. (Results) The number of urological operations decreased to 847, 862, and 768 in fiscal year 2018, 2019, and 2020, respectively. There was no significant change in the number of surgeries for malignant tumors in fiscal year 2020, but the number of surgeries for benign diseases decreased. The number of emergency operations tended to increase in fiscal year 2020. The number of urological hospitalized patients in fiscal year 2018, 2019, and 2020 decreased to 653, 690, and 533, and the average length of stay was shortened to 8.4, 8.8, and 8.1 days, respectively. The outpatient and inpatient unit prices per patient when fiscal year 2018 was set to 100 were increasing to 119.5 and 104.9, 133.7 and 119.1 in fiscal year 2019 and 2020, respectively. (Conclusion) It is thought that the spread of COVID-19 has clarified the function and characteristics of our hospital in community medicine.

Response to Pembrolizumab After Dose-Reduced Cisplatin Plus Gemcitabine Chemotherapy Is Inferior to That After Carboplatin Plus Gemcitabine Chemotherapy in Cisplatin-Unfit Patients With Advanced Urothelial Carcinoma.

INTRODUCTION: Response to pembrolizumab after first-line chemotherapy is vital to prolonged survival in advanced, unresectable, and/or metastatic urothelial carcinoma (aUC). However, there are sparse clinical data on host-tumor immune modification by first-line platinum-based chemotherapy. This study investigated the association between response to first-line gemcitabine plus cisplatin (GC) or carboplatin (GCarbo) chemotherapy and response to subsequent pembrolizumab treatment. PATIENTS AND METHODS: A multicenter-derived database registered 454 patients diagnosed with aUC between 2008 and 2020. Of these, 108 patients who received first-line GC or GCarbo followed by second-line or later pembrolizumab were eligible for investigation and were classified into 3 groups: 48 receiving full-dose GC, 21 receiving dose-reduced GC, and 39 receiving GCarbo. Overall survival (OS) was calculated using the Kaplan-Meier method and compared using the log-rank test. Possible factors associated with the response to pembrolizumab were evaluated using binary logistic regression methods. RESULTS: The rate of patients undergoing surgical removal of the primary organ was higher and creatinine clearance was lower in the dose-reduced GC and GCarbo groups than in the full-dose GC groups. Pembrolizumab responders had significantly better survival benefits than nonresponders. The rate of pembrolizumab responders was much higher in first-line chemotherapy responders than in first-line chemotherapy nonresponders. In contrast to the full-dose GC and GCarbo groups, the pembrolizumab responder rate was lower, and no association was observed between response to first-line chemotherapy and response to pembrolizumab in the dose-reduced GC group. CONCLUSION: Cisplatin and carboplatin may play an important role in the antitumor immune response, which could impact the outcome of subsequent pembrolizumab treatment. Given that the rate of response to pembrolizumab after dose-reduced GC chemotherapy was relatively low, this regimen is not recommended for cis-unfit patients with aUC. Further studies are required to understand the mechanisms responsible for the cross-reactivity of platinum and immune checkpoint inhibitors.

Relationship between Oral Hypofunction, and Protein Intake: A Cross-Sectional Study in Local Community-Dwelling Adults.

Few studies have investigated the relationship between nutritional status and comprehensive assessment of oral hypofunction, especially protein intake-related sarcopenia. Thus, we explored these relationships in a large-scale cross-sectional cohort study using the seven-item evaluation for oral hypofunction and Diet History Questionnaire for nutritional assessment. We used the data from 1004 individuals who participated in the 2019 health survey of the residents of Tarumizu City, Kagoshima Prefecture, Japan for analysis. We found that individuals with oral hypofunction were significantly older with a lower skeletal muscle index. Although there were few foods that had a significant difference between the groups with and without oral hypofunction, the consumption of beans and meats was significantly lower in women and men in the oral hypofunction group, respectively. According to the lower limit of the tentative dietary goal defined in Japan, comprehensive evaluation of oral hypofunction was significantly and independently associated with protein intake in both men and women (odds ratio, 1.70; 95% confidence interval, 1.21-2.35). In conclusion, we found that oral hypofunction was associated with targeted protein intake for sarcopenia and frailty prevention in middle-aged and older community-dwelling adults. Comprehensive evaluation of oral function with intervention in cases of hypofunction could inform clinicians to better prevent sarcopenia.

Association of Oral Hypofunction with Frailty, Sarcopenia, and Mild Cognitive Impairment: A Cross-Sectional Study of Community-Dwelling Japanese Older Adults.

Oral hypofunction is a new concept that addresses the oral function of older adults. Few studies have investigated the relationship between oral hypofunction and general health conditions such as frailty, sarcopenia, and mild cognitive impairment. This paper explores these relationships in a large-scale, cross-sectional cohort study. The relationships of oral hypofunction with frailty, sarcopenia, and mild cognitive impairment were examined using data from 832 individuals who participated in the 2018 health survey of the residents of Tarumizu City, Kagoshima Prefecture, Japan. Individuals with frailty, sarcopenia, and mild cognitive impairment had significantly higher rates of oral hypofunction. Frailty was independently associated with deterioration of the swallowing function (odds ratio 2.56; 95% confidence interval, 1.26-5.20), and mild cognitive impairment was independently associated with reduced occlusal force (odds ratio 1.48; 95% confidence interval, 1.05-2.08) and decreased tongue pressure (odds ratio 1.77; 95% confidence interval, 1.28-2.43). There was no independent association found between sarcopenia and oral function. In conclusion, early intervention for related factors such as deterioration of the swallowing function in frailty, reduced occlusal force, and decreased tongue pressure in mild cognitive impairment could lead to the prevention of general hypofunction in older adults.