Investigation of risk factors for vaginal dehiscence and development of small bowel evisceration after robot-assisted radical cystectomy for female bladder cancer and an improved vaginal reconstruction technique to prevent its onset.

Transvaginal organ prolapse, such as small bowel evisceration, is a rare complication after radical cystectomy (RC) in female patients with invasive bladder cancer, However, it often requires emergency surgical repair. Here, we describe our experience with such a case and a review of similar previously reported cases, along with evaluation of the risk factors. We also propose a vaginal reconstruction technique to prevent this complication during robot-assisted laparoscopic radical cystectomy (RARC). A total of 178 patients who underwent laparoscopic radical cystectomy (LRC) or RARC were enrolled, 34 of whom (19%) were female. One of the 34 female patients had transvaginal small bowel evisceration after RARC. We evaluated our case and six such previously reported cases, to determine vaginal reconstruction techniques during RARC to prevent this complication postoperatively. Median age of these cases was 73 (51-80) years, and all patients were postmenopausal. The median time to small bowel evisceration was 14 (6-120) weeks postoperatively. In addition, we changed the methods of the vaginal reconstruction technique during RARC from the conventional side-to-side closure technique to the improved caudal-to-cephalad closure technique. Since implementing this change, we have not experienced any cases of vaginal vault dehiscence or organ prolapse. Transvaginal small bowel evisceration after RC can easily become severe. Therefore, all possible preventive measures should be taken during RARC. We believe that our vaginal reconstruction techniques might reduce the risk of developing this complication.

EGFR-mutated lung adenocarcinoma with choroidal oligometastasis during treatment with gefitinib: a case report.

The patient was a 74-year-old woman who was diagnosed with lung adenocarcinoma, clinical Stage IIIA. Induction chemoradiation was performed followed by right upper lobectomy and lymph node dissection. Because of positive pleural effusion cytology, which was proven after surgery, the patient was diagnosed with pathological Stage IVA with EGFR L858R mutation. At 17 months after the administration of gefitinib, left choroidal metastasis appeared. Stereotactic irradiation and ruthenium small-beam radiation were effective; however, the metastatic lesion showed regrowth 7 months after these treatments. Because the patient's choroidal oligometastasis was resistant to conservative therapy, left ophthalmectomy was performed. EGFR mutations (L858R and E709K) were detected in the resected choroidal tumor. The patient continued to take gefitinib. However, a neoplastic lesion developed on the optic nerve adjacent to the resected posterior eye segment. The lesion was treated with stereotactic radiation, gefitinib was switched to afatinib 30 mg, and the patient remains alive and disease free for 11 months.

Intraoperative Blood Flow Evaluation Using Indocyanine Green Fluorescence Angiography for the Surgical Reconstruction of a Hilar Renal Artery Aneurysm.

Surgical reconstruction is one of the standard treatments for renal artery aneurysm. However, its intraoperative evaluation is sometimes difficult depending on the operative field, aneurysm morphology, and peripheral blood vessel distribution. This case demonstrated that after renal artery reconstruction, indocyanine green fluorescence angiography is used to evaluate the results of repairing. This method is useful in visceral aneurysm evaluation not only for assessing reconstructed blood flow but also for confirming tissue perfusion of the renal parenchyma.

Effects of percutaneous cryoablation for renal tumor on overall and split renal function.

PURPOSE: To evaluate retrospectively the influence of percutaneous cryoablation for small renal tumors on total and affected kidney function and risk factors associated with worsening function of the affected kidney. MATERIALS AND METHODS: Between April 2016 and March 2022, 27 patients who underwent cryoablation for small renal tumors at our institution participated in this study, which investigated time-dependent changes in postoperative renal function. We evaluated estimated glomerular filtration rates (eGFRs) and split renal function revealed by scintigraphy using 99 m technetium-mercaptoacetyltriglycine (99mTc-MAG3) before cryoablation and at 1 week, 1 month, and 6 months after cryoablation. Numerous variables were analyzed to assess risk factors for worsening renal function. RESULTS: Baseline eGFR (mean ± standard deviation) was 56.5 ± 23.7 mL/min/1.73 m2 (mean ± SD; range, 20.5-112.5). Mean eGFRs at 1 week, 1 month, and 6 months after cryoablation were 57.4 ± 24.5 (19.1-114.9), 57.1 ± 25.1 (21.5-114.9), and 53.8 ± 23.9 mL/min/1.73 m2 (20.0-107.5), respectively. Changes were statistically insignificant (p = 1.0000, = 0.6749, and = 0.0761, respectively). Regarding split renal function, mean baseline contribution of the affected kidney determined by 99mTc-MAG3 was 49.7% ± 6.0% (38.8-63.3%); these rates at 1 week, 1 month, and 6 months after cryoablation were 43.7% ± 8.8 (29.1-70.6%), 46.2% ± 7.7% (32.6-70.3%), and 46.0% ± 8.5% (32.5-67.6%), respectively. Differences from baseline were significant for all periods (p < 0001, < 0001, = 0.0001, respectively). Serum C reactive protein and lactate dehydrogenase at 1 day following cryoablation, tumor's nearness to the collecting system or sinus, and volume of ablated normal renal parenchyma were significantly correlated with decreased contributions of the affected kidney by > 10% after cryoablation. CONCLUSION: Unlike total renal function, affected kidney function could worsen after cryoablation.

Albuterol Delivery via In-Line Intrapulmonary Percussive Ventilation Superimposed on Invasive Ventilation in an Adult Lung Model.

BACKGROUND: Intrapulmonary percussive ventilation (IPV) is frequently used for airway clearance, together with delivery of aerosolized medications. Drug delivery via IPV alone increases with decreasing percussion frequency and correlates with tidal volume (VT), whereas drug delivery via IPV during invasive ventilation is not well characterized. We hypothesized that drug delivery via IPV-invasive ventilation would differ from IPV alone due to control of ventilation by invasive ventilation. METHODS: An adult ventilator circuit was used for IPV-invasive ventilation. A normal or a diseased lung model was configured to airway resistance of 5 cm H2O/L/s and lung compliance of 100 mL/cm H2O or to airway resistance of 20 cm H2O/L/s and lung compliance of 50 mL/cm H2O, respectively. The ventilator settings were the following: pressure control continuous mandatory ventilation mode, 10 breaths/min; PEEP, 5 cm H2O; FIO2 , 0.21; inspiratory time, 1 s; no bias flow; and inspiratory pressure, 10 or 15 cm H2O for the normal or the diseased lung model, respectively, to reach VT 500 mL with IPV off. Albuterol nebulized from an IPV device was captured in a filter placed before the lung model and quantitated by spectrophotometry. RESULTS: The maximum efficiency of albuterol delivery via IPV-invasive ventilation was not different from that via IPV alone (mean ± SD of loading dose, 3.7 ± 0.2% vs 4.2 ± 0.3%, respectively; P = .12). The mean ± SD albuterol delivery efficiency with IPV-invasive ventilation was lower for the diseased lung model versus the normal model (1.6 ± 0.3% vs 3.2 ± 0.5%; P < .001), which increased with decreasing percussion frequency. In contrast, the mean ± SD VT was lower for the normal lung model versus the diseased model (401 ± 14 mL vs 470 ± 11 mL; P < .001). CONCLUSIONS: Albuterol delivery via IPV-invasive ventilation was modulated by percussion frequency but was not increased with increasing VT. The delivery efficiency was not sufficiently high for clinical use, in part due to nebulizer retention and extrapulmonary deposition.

Challenges in Robotic Lung Lobectomy through the Anterior Approach.

PURPOSE: Robot-assisted thoracic surgery (RATS) has become popular because of its minimally invasive nature and reduced burden on surgeons. The anterior approach (AA) is beneficial because it utilizes the same field of view and procedures as thoracotomy and video-assisted thoracic surgery, although the disadvantages are less well-known. METHODS: We retrospectively examined 35 consecutive patients who underwent RATS lobectomy via the AA, focusing on clinical factors and postoperative complications. RESULTS: The study included 12 males and 23 females with a median console time of 177 (120-346) min, median blood loss of 0 (0-100) mL, and median stapler usage of 5 (2-10) units. Postoperative complications, classified as Clavien-Dindo grade ≥III, included three cases of grade IIIa (prolonged air leakage) and one case each of grade IIIb and grade IVa (middle lobe torsion and ventricular arrhythmia). The influence of stapling device operation cannot be ruled out in prolonged air leakage and middle lobe torsion. A moderate correlation (correlation coefficient = 0.492, p = 0.003) was observed between console time and the number of staplers used. CONCLUSION: Although no severe incidence of vascular injury was observed with the AA, complications related to the use of stapling devices were noted.

Osimertinib as first-line treatment for recurrent lung cancer patients with EGFR mutation.

Background: Although osimertinib was approved as adjuvant therapy for lung cancer patients with EGFR mutation in various countries, there is still some ongoing debate as osimertinib has been approved based on disease-free survival (DFS) rather than overall survival (OS). We curated a case series in which we documented patterns of recurrence and efficacy and safety of osimertinib after recurrence. Methods: Patients who received osimertinib as first-line treatment for postoperative recurrence between September 2018 and January 2023 were included. Clinicopathological factors, duration of osimertinib treatment (DoT), and adverse events were collected and analyzed. Results: Twenty patients received osimertinib [male, n=6; median age, 75 years (range, 55-85 years)]. The EGFR mutation type was L858R in 11 patients and exon 19 deletion in eight patients. The performance status (PS) was 0 or 1 in all but two patients, who had symptomatic brain metastasis and were therefore PS 3. The first site of postoperative recurrence was locoregional in five patients and distant in 15 patients, including seven with brain metastasis. As of February 2023, 10 patients were still on osimertinib, including three with brain metastasis. Patients with brain metastasis or poor PS had a considerably shorter DoT than their counterparts. Three patients with symptomatic brain metastasis or leptomeningeal metastasis initially responded to osimertinib, but all died of disease progression. Five patients discontinued osimertinib due to serious adverse effects (pneumonitis, drug eruption, and heart failure). Conclusions: Although osimertinib exerts great disease control, even in patients with brain metastasis or poor PS, their presence was associated with a poor prognosis, even with osimertinib treatment. Therefore, adjuvant osimertinib is recommended unless contraindicated.

Giant benign intrathoracic schwannoma: a decade-long progression towards fatality.

BACKGROUND: Intrathoracic neurogenic tumors arise from sympathetic nerve trunks and intercostal nerves; more than 90% are benign. Schwannomas are the most common histological variety, but fatalities due to giant schwannomas are rare. CASE PRESENTATION: We report a case of a 65-year-old woman who presented with chest pain and cough. Computed tomography (CT) revealed a large left chest wall mass of 130-mm in size, and the patient was referred to our department. Tumor biopsy was performed under local anesthesia, and a diagnosis of schwannoma was made. Ten years previously, a 30-mm tumor had been noted in the left third intercostal space by a previous doctor, but follow-up had been interrupted owing to depressive disorder. Although we planned to perform intercostal artery embolization followed by chest wall tumor resection, the patient did not consent to surgery due to uncontrolled depression. After four months, she developed respiratory failure caused by compression due to an enlarged tumor and died. Autopsy also revealed a benign schwannoma with no malignant findings. CONCLUSIONS: Although schwannomas are benign tumors, there are some very rare cases in which they can become huge and life-threatening. Therefore, a benign tumor should not be neglected, and if surgery is not possible at the time of diagnosis, a regular follow up is necessary, in order not to miss the right timing for surgery.

Significance of programmed death-ligand 1 expression in resected lung cancer and its relationship with EGFR mutation.

BACKGROUND: Several studies have reported that the high expression of programmed death-ligand 1 (PD-L1) within tumor cells predicts a poor prognosis. However, the relationship between the PD-L1 expression and lymph node metastasis or driver mutations in lung cancer remains poorly understood. METHODS: A total of 356 consecutive patients who underwent surgical resection for primary lung cancer were included in the study. There were 268 adenocarcinomas including 100 EGFR mutations, 67 squamous cell carcinomas (Sq), and 21 other histologies. The high expression of PD-L1 was defined as a tumor proportion score (TPS) of ≥50. The relationship between the PD-L1 expression and clinicopathological factors and recurrence-free survival (RFS) was analyzed. RESULTS: The PD-L1 expression was high in 75 patients. It was significantly related to smoking history, Sq histology, driver mutation negative, elevated serum carcinoembryonic antigen levels, and lymph node metastasis. Among patients with driver mutations, a high PD-L1 TPS was found in patients with EGFR G719X mutation. A significant difference in RFS was observed in adenocarcinoma patients. A multivariate analysis of adenocarcinoma cases revealed that tumor size and lymph node metastasis were independent prognostic factors for poor RFS, while the PD-L1 expression was not. A logistic regression analysis revealed that the absence of driver mutations, lymph node metastasis, and a history of smoking were significantly associated with the high expression of PD-L1. CONCLUSION: Lymph node metastasis was positively related with the high expression of PD-L1, resulting in poor RFS. A high PD-L1 TPS was observed in patients with the EGFR G719X mutation.

Possible involvement of brain hydrogen sulphide in the inhibition of the rat micturition reflex induced by activation of brain alpha7 nicotinic acetylcholine receptors.

We previously reported that brain α7 nicotinic acetylcholine receptors inhibited the rat micturition reflex. To elucidate the mechanisms underlying this inhibition, we focused on the relationship between α7 nicotinic acetylcholine receptors and hydrogen sulphide (H2S) because we found that H2S also inhibits the rat micturition reflex in the brain. Therefore, we investigated whether H2S is involved in the inhibition of the micturition reflex induced by the activation of α7 nicotinic acetylcholine receptors in the brain. Cystometry was performed in male Wistar rats under urethane anesthesia (0.8 g/kg, ip) to examine the effects of icv pre-treated GYY4137 (H2S donor, 1 or 3 nmol/rat) or aminooxyacetic acid (AOAA; non-selective H2S synthesis inhibitor, 3 or 10 µg/rat) on PHA568487 (α7 nicotinic acetylcholine receptor agonist, icv)-induced prolongation of intercontraction intervals. PHA568487 administration at a lower dose (0.3 nmol/rat, icv) had no significant effect on intercontraction intervals, while under pre-treatment with GYY4137 (3 nmol/rat icv), PHA568487 (0.3 nmol/rat, icv) significantly prolonged intercontraction intervals. PHA568487 at a higher dose (1 nmol/rat, icv) induced intercontraction interval prolongation, and the PHA568487-induced prolongation was significantly suppressed by AOAA (10 µg/rat, icv). The AOAA-induced suppression of the PHA568487-induced intercontraction interval prolongation was negated by supplementing H2S via GYY4137 at a lower dose (1 nmol/rat, icv) in the brain. GYY4137 or AOAA alone showed no significant effect on intercontraction intervals at each dose used in this study. These findings suggest a possible involvement of brain H2S in inhibiting the rat micturition reflex induced by activation of brain α7 nicotinic acetylcholine receptors.

Vibegron 50 mg Once Daily Improves OABSS, OAB-q SF Score in OAB Patients ≥80 Years Old in Real-World Clinical Settings and Switching from Other OAB Drugs May Reduce Residual Urine Volume.

Objective: The treatment effects of vibegron have not previously been evaluated in a prospective, non-interventional observational study of elderly Japanese patients, particularly those ≥80 years old. In addition, no reports have referred to residual urine volume in switching cases. We therefore grouped patients by condition and investigated the treatment effects of vibegron on Overactive Bladder Symptom Score (OABSS), Overactive Bladder Questionnaire Short Form (OAB-q SF), and residual urine volume in each group. Methods: This multicenter, prospective, non-interventional, observational study consecutively enrolled OAB patients with total OABSS score ≥3 and OABSS question 3 score ≥2. Sixty-three patients from six centers were recruited. Vibegron 50 mg once daily was administered for 12 weeks as first-line monotherapy (first-line group), monotherapy switching from antimuscarinics or mirabegron due to failure of prior therapy (no washout period), or combination therapy with antimuscarinics (second-line group). OABSS, OAB-q SF, and residual urine volume were collected after 4 and 12 weeks. Adverse events were also recorded at each visit. Results: Of the 63 patients registered, 61 were eligible for analysis (first line, n=36; second line, n=25). The OABSS, excluding daytime frequency scores, and OAB-q SF scale showed significant improvement in all conditions. Switching from mirabegron to vibegron significantly reduced residual urine volume. No serious treatment-related adverse events were encountered. Conclusion: Vibegron 50 mg once daily significantly improved OABSS and OAB-q SF even in patients ≥80 years old. Notably, switching from mirabegron to vibegron resulted in significant improvements to residual urine volume.

Variant spectrum of von Hippel-Lindau disease and its genomic heterogeneity in Japan.

Von Hippel-Lindau (VHL) disease is an autosomal dominant, inherited syndrome with variants in the VHL gene, causing predisposition to multi-organ neoplasms with vessel abnormality. Germline variants in VHL can be detected in 80-90% of patients clinically diagnosed with VHL disease. Here, we summarize the results of genetic tests for 206 Japanese VHL families, and elucidate the molecular mechanisms of VHL disease, especially in variant-negative unsolved cases. Of the 206 families, genetic diagnosis was positive in 175 families (85%), including 134 families (65%) diagnosed by exon sequencing (15 novel variants) and 41 (20%) diagnosed by multiplex ligation-dependent probe amplification (MLPA) (one novel variant). The deleterious variants were significantly enriched in VHL disease Type 1. Interestingly, five synonymous or non-synonymous variants within exon 2 caused exon 2 skipping, which is the first report of exon 2 skipping caused by several missense variants. Whole genome and target deep sequencing analysis were performed for 22 unsolved cases with no variant identified and found three cases with VHL mosaicism (variant allele frequency: 2.5-22%), one with mobile element insertion in the VHL promoter region, and two with a pathogenic variant of BAP1 or SDHB. The variants associated with VHL disease are heterogeneous, and for more accuracy of the genetic diagnosis of VHL disease, comprehensive genome and DNA/RNA analyses are required to detect VHL mosaicism, complicated structure variants and other related gene variants.

Primary adrenal Ewing's sarcoma family of tumors with tumor thrombus of the inferior vena cava: a case report.

BACKGROUND: Ewing's sarcoma is a malignant neoplasm that mainly occurs in skeletal tissue but can rarely arise in soft tissues. Recently, small round cell tumors (including Ewing's sarcoma) caused by chromosomal translocations have been collectively termed Ewing's sarcoma family of tumors. We report a rare case of primary adrenal Ewing's sarcoma family of tumors with tumor thrombus. CASE PRESENTATION: A 22-year-old Asian woman was referred to our hospital with a left retroperitoneal tumor 19 cm in diameter. Tumor thrombus was identified from the left adrenal vein to the inferior vena cava, infiltrating the right atrium. Total tumor excision with left adrenalectomy, nephrectomy, and thrombectomy was performed under hypothermic circulatory arrest, followed by seven courses of adjuvant chemotherapy. The patient has shown no signs of recurrence as of 26 months postoperatively. CONCLUSION: Radical surgery combined with systemic chemotherapy may contribute to good prognosis in patients with primary adrenal Ewing's sarcoma family of tumors.

Metabolic shift towards oxidative phosphorylation reduces cell-density-induced cancer-stem-cell-like characteristics in prostate cancer in vitro.

Numerous cancer patients undergoing conventional cancer therapies such as radiotherapy, chemotherapy and surgical tumour removal face relapses several years or even decades later. This may be due to the presence of cancer stem cells (CSCs) that survived said therapies. In this study, we aimed to uncover the relationship between cell density and CSCs, and the role of the Warburg effect in regulating CSC-like characteristics. A prostate cancer cell line, PC3, was used in this study. To investigate the Warburg effect effect and CSC-like characteristics in prostate cancer, we measured the expression levels of glycolysis and OXPHOS-related genes, and performed spheroid forming, cell viability and various glycolysis and OXPHOS-assays. We observed that increased cell density caused a metabolic shift from glycolysis to OXPHOS and higher CSC-like characteristics. However, the use of dichloroacetate (DCA), an inhibitor of the Warburg effect, significantly inhibited the cell-density-induced metabolic shift and CSC-like characteristics. Changes in cell density strongly influenced the preferred metabolic pathway of prostate cancer cells, regulating their CSC-like characteristics. It is possible that DCA, an inhibitor of the Warburg effect, could be a novel drug used to treat CSCs by distinguishing Warburg effect, preventing future cancer relapses.

[Segmentectomy for Lung Cancer Using Indocyanine Green( ICG)].

The most important issues in the segmentectomy for lung cancer, are the accurate establishment of the suture line and to reduce local recurrence at the resection margin. There are two methods:bronchial dominance as an indicator and intravenous indocyanine green (ICG) as an indicator of blood flow dominance. We have been performing identification by ICG since 2020. After the pulmonary arteriovenous and bronchus are resected, ICG is injected intravenously, and the borders between fluorescent and non-fluorescent area is identified using a ICG thoracoscope, and are resected using an electro-surgical unit or stapler. After that, additional ICG is administered, pulmonary blood flow is checked, and if an uncontaminated area is identified, an additional resection is performed. We have retrospectively reviewed 16 cases of ICG method for lung cancer( all at clinical stageⅠ) performed since January 2020, and no recurrence has been observed. We present the details of these cases and report the usefulness of the ICG fluorescence system.

Cyclin-dependent kinase (CDK) 4/6 inhibition in non-small cell lung cancer with epidermal growth factor receptor (EGFR) mutations.

BACKGROUND: Lung cancer is the leading cause of cancer death worldwide, and EGFR mutation is the most common genetic alteration among Asian patients with lung adenocarcinoma. While osimertinib has been shown to be effective in lung cancer patients with EGFR mutation, the majority of patients eventually develop acquired resistance to treatment. We explored the significance of the cyclin D1 expression in patients with EGFR mutation and the potential efficacy of adding abemaciclib, a cyclin-dependent kinase (CDK) 4/6 inhibitor, simultaneously with osimertinib in vitro. MATERIALS AND METHODS: Immunohistochemical staining, using an anti-cyclin D1 antibody, of specimens from 83 patients with EGFR mutation (male, n = 27; pStage 0-I, n = 71) who were treated by surgical resection between 2017 and 2020, and the relationship between the cyclin D1 expression and clinicopathological factors was analyzed. Additionally, the combined effect of osimertinib and abemaciclib in lung cancer cell lines were analyzed using a growth inhibition test, and the signaling pathway underlying the combined effect was investigated. RESULTS: Cyclin D1 was negative in 18.1% of patients with EGFR mutation, and cyclin D1 negativity was associated with pStage ≥ II (p = 0.02), lymph node metastasis (p = 0.001), and lymphatic invasion (p = 0.01). The cyclin D1-negative group had significantly shorter recurrence-free survival (p = 0.02), although this difference disappeared when limited to pN0 patients. In EGFR mutated cell lines, the combination of osimertinib and abemaciclib demonstrated synergistic effects, which were thought to be mediated by the inhibition of AKT phosphorylation. CONCLUSION: Combination therapy with CDK4/6 inhibitors and EGFR-TKIs may be a promising approach.

Tracheal injury from dog bite in a child.

BACKGROUND: Dog bites associated with the head and neck area in children are a common problem. Most of the lacerations are found in the upper lip and the nose region, and tracheal injury is rare [1]. Tracheal injury requires prompt and accurate diagnosis and treatment to rescue the patient. Especially in children, securing the airway is often more difficult than in adults because of their short neck and narrow trachea. In this report, we experienced a pediatric case of multiple dog bites with tracheal injuries in the neck. CASE PRESENTATION: We report the case of a 3-year-old girl who presented with multiple dog bites. There were multiple wounds on the head, face, neck, and anterior chest, and air leakage was observed from the cervical wound at the time of transfer. It was difficult to perform oral endotracheal intubation, therefore, we extended the neck wound, probed the trachea with finger, and inserted a tracheal tube directly from the cervical wound in the emergency room. Tracheoplasty and another wound cleansing were performed in the operating room. The patient was discharged on the 18th day after surgery, without further complications. CONCLUSION: Tracheal injury from a dog bite is rare. It is important to prompt and accurate diagnosis and treatment. Children should be especially careful because of their short necks and narrow tracheas.

Ureteral rupture with retroperitoneal urinoma caused by peritoneal metastases of gastric cancer.

We describe the rare case of a patient with ureteric rupture during systemic drug treatment for peritoneal metastases of gastric cancer, who underwent double-J stent placement. A 66-year-old man with gastric cancer was referred to the authors' hospital. Esophagogastroduodenoscopy showed an irregular elevated lesion with thickened gastric folds, and biopsy specimens revealed a poorly differentiated adenocarcinoma. Abdominal contrast-enhanced computed tomography (CT) revealed extensive wall thickening with homogeneous enhancement of the stomach, enlarged lymph nodes in the perigastric area, and nodules in the peritoneal cavity, suggesting peritoneal metastases. The clinical diagnosis was cT4N2M1 with peritoneal metastases, and the patient received chemotherapy (S-1 plus oxaliplatin). After six courses of chemotherapy, the patient presented to the emergency outpatient department with a complaint of acute severe pain in the left lower back. Emergency abdominal contrast-enhanced CT showed extravasation of the contrast medium from the left upper ureter in the periureter area along with the retroperitoneum, and there was no mass lesion or stone in the kidney, ureter, or bladder. A double-J stent was placed under cystoscopic guidance, and no resistance was felt when the stent was inserted. The patient's postprocedural course was uneventful, and he received ramucirumab in combination with paclitaxel after double-J stent placement. However, 2 months later, systemic drug treatment was discontinued because of loss of appetite and increased general fatigue and changed to the best supportive care. His general condition gradually deteriorated, and he died 3 months after the ureteral rupture. Prompt interventions, including retrograde placement of ureteral stents with concurrent use of antibiotics, will reduce mortality and morbidity in this rare entity.

Discontinuation of pembrolizumab for advanced urothelial carcinoma without disease progression: Nationwide cohort study.

Pembrolizumab, an anti-programmed death 1 monoclonal antibody, has revolutionized the treatment of metastatic urothelial carcinoma. However, the optimal treatment duration for treatment responders has not been established. To address this, we retrospectively assess the treatment outcomes and duration of pembrolizumab for patients whose best response was complete response (CR) or partial response (PR) in a Japanese nationwide cohort of platinum-refractory metastatic urothelial carcinoma. Of 203 patients whose best response was CR or PR, 83 patients discontinued pembrolizumab before progression. The median pembrolizumab treatment duration was 6.9 months. The 2-year relapse-free survival (RFS), treatment-free survival, and OS rates after discontinuation were 49.0%, 57.4%, and 74.5%, respectively. CR, higher hemoglobin levels, and a better Eastern Cooperative Oncology Group performance status at the time of discontinuation were associated with significantly better RFS. Pembrolizumab was re-administered to 12 patients. Pembrolizumab re-challenge resulted in CR, PR, stable disease, and progressive disease in six, three, two, and one patient, respectively. Propensity score-matched landmark analysis revealed no significant OS difference between patients who continued or discontinued pembrolizumab at 6, 12, and 18 months (p = 0.91, 0.99, and 0.25, respectively). Our findings demonstrated that patients with objective responses had favorable survival outcomes and suggested that pembrolizumab could be discontinued safely in this population. This study should drive further efforts to optimize the treatment duration for pembrolizumab responders.

Clinical evaluation of urine laminin-γ2 monomer as a potent biomarker for non-muscle invasive bladder cancer.

BACKGROUND: To evaluate whether urine laminin-γ2 monomer (Ln-γ2m) offers a useful biomarker for patients with non-muscle-invasive bladder cancer (NMIBC). METHODS: Participants comprised 297 patients, including 111 patients with NMIBC, 136 patients with benign genitourinary disease (BD) and 50 healthy donors (HD). Urine Ln-γ2m was prospectively measured and accuracy was analyzed. Receiver operating characteristic (ROC) curves were determined and area under the ROC curve (AUC) was calculated for urine Ln-γ2m, and compared to those of traditional urine tumor markers such as nuclear matrix protein 22 (NMP22), bladder tumor antigen (BTA) and cytology. The net benefits of combining urine markers were analyzed by decision curve analysis. RESULTS: Mean urine Ln-γ2m was significantly higher in NMIBC than in BD or HD. The AUC for urine Ln-γ2m was significantly higher than those for urine NMP22, BTA or cytology when comparing NMIBC with HD. In patients with low-grade NMIBC, the AUC for urine Ln-γ2m was higher than the AUCs for NMP22, BTA or cytology. A net benefit of combined examination using urine Ln-γ2m/uCRN with NMP22 was demonstrated. CONCLUSION: These results suggest urine Ln-γ2m as a potentially useful biomarker for NMIBC, particularly in cases of low-grade cancer.