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Abstract Background Chemotherapy‐induced anorexia is a common occurrence in patients undergoing treatment for advanced lung cancer. However, the relationship between chemotherapy‐induced anorexia and weight loss during platinum‐based chemotherapy combined with immune checkpoint inhibitors is unclear. This study explored the relationship between chemotherapy‐induced anorexia and therapeutic outcomes in patients with stage IV non‐small‐cell lung cancer undergoing platinum‐based chemotherapy combined with immune checkpoint inhibitors. Methods The study retrospectively reviewed the medical records of 106 patients with stage IV non‐small‐cell lung cancer treated with platinum‐based chemotherapy and immune checkpoint inhibitors between January 2019 and October 2022. The incidence of weight loss and its association with treatment efficacy was assessed in the chemotherapy‐induced anorexia group. Chemotherapy‐induced anorexia, nausea, and vomiting were evaluated using Common Terminology Criteria for Adverse Events v 5.0. Progression‐free and overall survival were used to measure treatment efficacy. Results Chemotherapy‐induced anorexia was observed in 13.2% of patients. These patients exhibited significant weight loss at 6 and 9 weeks after treatment initiation compared to those in the non‐chemotherapy‐induced anorexia group. Progression‐free and overall survival were shorter in the chemotherapy‐induced anorexia group than in the non‐chemotherapy‐induced anorexia group, but the difference was not statistically significant. Conclusions Chemotherapy‐induced anorexia was associated with significant weight loss and reduced treatment efficacy in patients with stage IV non‐small‐cell lung cancer. These results highlight the importance of implementing robust supportive care for chemotherapy‐induced anorexia to mitigate weight loss and uphold treatment effectiveness during platinum‐based chemotherapy combined with immune checkpoint inhibitors.

Introduction Pelvic arteriovenous malformations are rare in male patients. We present a case of pelvic arteriovenous malformation involving the seminal vesicle. Case presentation A 58‐year‐old man was diagnosed with pelvic arteriovenous malformation that involved the left seminal vesicle by angiography. The patient underwent three embolization procedures and made favorable progress after the embolizations. Conclusion Herein, we report a rare case of pelvic arteriovenous malformation involving the seminal vesicle treated by embolizations with good outcome.

Abstract Background The AmoyDx Pan lung cancer PCR panel (AmoyDx PLC panel) has been approved as a companion diagnostic tool for multiple anticancer agents in patients with non‐small cell lung cancer (NSCLC). However, the suitability of cytology specimens as samples for the AmoyDx PLC panel remains unclear. We evaluated the performance of frozen cell pellets from cytology specimens (FCPs) in the Amoy 9‐in‐1 assay, a preapproval assay of the AmoyDx PLC panel. Methods We retrospectively collected data of NSCLC patients enrolled in LC‐SCRUM‐Asia from the Shizuoka Cancer Center between September 2019 and May 2021. Results A total of 49 cases submitted FCPs for evaluation of oncogenic driver alterations and were assessed using Amoy 9‐in‐1 and next‐generation sequencing (NGS) assays. The success rates of DNA and RNA analyses using the Amoy 9‐in‐1 were both 100%, compared with 86% and 45%, respectively, using NGS assays. Oncogenic driver alterations were detected in 27 (55%) and 23 (47%) patients using Amoy 9‐in‐1 and NGS, respectively. No inconsistent results were observed among 19 cases in which both assays showed successful detection. In the remaining 30 cases, 10 had inconsistent results: nine oncogenic driver alterations (3 MET, 2 ALK, 2 ROS1, and 2 KRAS) were detectable only in Amoy 9‐in‐1, and one epidermal growth factor receptor (EGFR) mutation was detectable only in NGS. Conclusion FCPs can be successfully used in the AmoyDx PLC panel, with higher success rate compared with the NGS assay. The AmoyDx PLC panel may be an option in cases when insufficient tissue sample is available for the NGS assay.

Introduction Patients with hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome have high risks of uterine and cutaneous leiomyomas and renal cell carcinoma (RCC), which are caused by germline mutation of the fumarate hydratase (FH) gene. RCC lesions are mostly high‐grade tumors with a poor prognosis. Case presentation A 37‐year‐old man who had previously undergone treatment for a left RCC was referred to our hospital with a diagnosis of right RCC. Robot‐assisted partial nephrectomy was performed, and the pathological diagnosis revealed fumarate hydratase (FH)‐deficient RCC. The left RCC, which was originally diagnosed as mucinous tubular and spindle cell carcinoma, was reviewed and diagnosed as FH‐deficient RCC. The patient's father and uncle both died of RCC, and the father's tumor was also immunohistochemically proven to be FH‐deficient RCC. Conclusion HLRCC‐related RCC should be considered in a differential diagnosis of young patients with a family history of RCC.

Abstract Background Which patients benefit from the addition of immune checkpoint inhibitors (ICIs) to chemotherapy for small cell lung cancer (SCLC) remains unclear. There have been few reports on the efficacy of ICIs based on conventional immunohistochemical neuroendocrine (NE) markers (synaptophysin, chromogranin A, and neural cell adhesion molecule [NCAM]). In the present study, we aimed to analyze the relationship between the expression of immunohistochemical NE markers and the efficacy of ICIs in patients with extensive disease (ED)‐SCLC, to assess whether conventional NE markers are predictive of ICIs. Methods Patients with untreated ED‐SCLC who received first‐line therapy at the Shizuoka Cancer Center between November 2002 and July 2021 were retrospectively reviewed. We evaluated the efficacy of first‐line chemotherapy according to the expression status of each immunohistochemical NE marker in patients treated with ICI plus chemotherapy (ICI‐chemo group) and with chemotherapy alone (chemo group). Results A total of 227 patients were included in the ICI‐chemo and chemo groups, respectively. The progression‐free survival (PFS) tended to be better in patients in the ICI‐chemo group than those treated with chemotherapy alone in patients with NE marker‐positive SCLC. In particular, it was statistically significant in patients with chromogranin A‐positive SCLC (p = 0.036). In patients with NE marker‐negative SCLC, no significant differences were observed in PFS between the two groups. There were no significant differences in overall survival (OS), regardless of the expression of any conventional NE marker. Conclusion Our study suggests that the efficacy of ICIs in addition to chemotherapy may be poor in patients with NE marker‐negative SCLC.

Abstract Background and Objective Chronic graft versus host disease (GVHD)‐associated myositis targeting skeletal muscle is a relatively rare but potentially debilitating complication following allogeneic hematopoietic stem cell transplantation (HSCT). We reviewed the clinicopathological features of GVHD‐associated myositis among patients receiving allogeneic HSCT to elucidate the cellular pathogenesis. Methods We retrospectively reviewed clinical data and muscle biopsy results from 17 consecutive patients diagnosed with GVHD‐associated myositis at our institution between 1995 and 2019. Immunostaining findings of GVHD‐associated myositis were compared to those of patients with anti‐tRNA‐synthetase antibody‐associated myopathy (ASM) (n = 13) and dermatomyositis (DM) (n = 12). Results The majority of patients with GVHD‐associated myositis showed subacute or chronic progression of mild to moderate limb weakness together with elevated serum creatine kinase. These patients also exhibited mild C‐reactive protein elevation but were negative for myositis‐related autoantibodies. Programmed death‐1 (PD‐1)‐positive cells were observed in muscle interstitium adjacent to myofibers expressing human leukocyte antigen (HLA)‐DR. The interstitium was also HLA‐DR‐positive, similar to biopsy samples from ASM patients but not DM patients. The proportions of HLA‐DR‐positive muscle fibers and PD‐1‐positive interstitial cells were significantly higher in GVHD and ASM samples than DM samples. The PD‐1‐positive cells were mostly CD‐8‐positive lymphocytes. Discussion GVHD‐associated myositis is characterized by HLA‐DR‐positive myofibers and infiltration of PD‐1‐positive lymphocytes. These features distinguish GVHD‐associated myositis from DM but not from ASM.

Introduction Condyloma acuminatum usually occurs in the external genitalia and rarely in the bladder mucosa. Here, we report a case of condyloma acuminatum of the bladder that was detected concurrently with urothelial carcinoma. Case presentation A 42‐year‐old man was referred to our urology department with positive urine cytology for urothelial carcinoma. Cystoscopy revealed a broad‐base nonpapillary bladder tumor. The patient underwent a transurethral resection of the bladder tumor. Pathological examination revealed urothelial carcinoma, high‐grade pT1, and concurrent resection of condyloma acuminatum. DNA was extracted from the paraffin‐embedded transurethral resection of the bladder tumor tissue specimens. HPV11 was detected in condylomas by PCR and in situ hybridization, whereas HPV was not detected in urothelial carcinomas. Conclusion We report a rare case of condyloma acuminatum of the bladder that was concurrently diagnosed with urothelial carcinoma from the same site.

Abstract Background Amrubicin (AMR) regimens have shown efficacy as second‐line treatment in patients with small cell lung cancer (SCLC); however, adverse events such as febrile neutropenia (FN) sometimes preclude their use. Further, the safety and efficacy of AMR with primary prophylactic pegfilgrastim (P‐PEG) have not been sufficiently evaluated. In this study, we evaluated the safety and efficacy of AMR with or without P‐PEG as second‐line chemotherapy for SCLC. Methods We retrospectively reviewed patients with SCLC who received AMR as second‐line chemotherapy at Shizuoka Cancer Center, between December 2014 and November 2021. Based on presence/absence of P‐PEG in their regimen, patients (n = 60) were divided into P‐PEG (n = 21) and non‐P‐PEG groups, and their clinical outcomes were evaluated. Results Median of AMR treatment cycles was five (range: 1–39 cycles) in P‐PEG group and four (range: 1–15 cycles) in non‐P‐PEG group. The incidence of FN (4.8% vs. 30.8%; p = 0.02) and AMR dose reduction because of adverse events (4.8% vs. 25.6%; p = 0.08) were lower in the P‐PEG group than in the non‐P‐PEG group. The objective response rates were 52.4% and 30.8%, and median progression‐free and overall survival were 4.7 and 3.0 months, and 9.6 and 6.8 months, in the P‐PEG and non‐P‐PEG groups, respectively. Conclusions AMR with P‐PEG as second‐line chemotherapy for SCLC reduced the incidence of FN at a maintained AMR dose intensity and was associated with favorable tumor responses and survival outcomes. P‐PEG should be considered for patients treated with AMR for SCLC including refractory relapsed SCLC.

Introduction Disseminated carcinomatosis of the bone marrow in prostate cancer is rare and has a poor prognosis. Although strong evidence suggests that novel hormonal agents improve the prognosis of metastatic prostate cancer, their effectiveness in cases of disseminated carcinomatosis of the bone marrow remains unclear. Case presentation We encountered two cases of prostate cancer with disseminated carcinomatosis of the bone marrow at the time of initial diagnosis. One patient was treated with enzalutamide, abiraterone, docetaxel, cabazitaxel, denosumab, and radium‐223 and died 38 months after the initial diagnosis. The other patient was treated with apalutamide and denosumab, and had progression‐free survival for 17 months after the initial diagnosis. Conclusion These results suggest that novel hormonal agents may improve the prognosis of prostate cancer even in patients with disseminated carcinomatosis of the bone marrow.

Introduction Intravesical Bacillus Calmette–Guérin immunotherapy is an effective treatment for non‐muscle‐invasive bladder cancer, which is occasionally associated with side effects and complications. The incidence of significant renal complications after intravesical Bacillus Calmette–Guérin immunotherapy is less than 2%. We report a case of renal granuloma after intravesical Bacillus Calmette–Guérin immunotherapy for bladder cancer, which radiologically resembled a papillary renal cell carcinoma. Case presentation A 65‐year‐old man, who had a medical history of urothelial carcinoma and received intravesical Bacillus Calmette–Guérin therapy, was referred to our Urology Department with a right renal tumor. Imaging findings suggested papillary renal cell carcinoma. Robot‐assisted partial nephrectomy was performed, and the histopathological examination revealed epithelioid cell granuloma, which were considered to be Bacillus Calmette–Guérin‐related renal granuloma. Conclusion Bacillus Calmette–Guérin‐related renal granuloma mimicking papillary renal cell carcinoma have been reported. We should consider the possibility of renal granulomas when encountering image abnormalities for patients treated with intravesical Bacillus Calmette–Guérin therapy.

Introduction Subcutaneous emphysema is a relatively common complication in laparoscopic surgery. However, airway obstruction secondary to subcutaneous emphysema is rare. Case presentation A 63‐year‐old woman with a 56‐mm left renal tumor underwent a robot‐assisted partial nephrectomy. The operative time was 155 min, the insufflation time was 108 min, and the estimated blood loss was 70 mL. The pneumoperitoneum pressure was maintained at 12 mmHg, except at 15 mmHg for 19 min during tumor resection. The end‐tidal CO2 was

Introduction We present a case of mucinous adenocarcinoma of the prostate with testicular and lung metastases following robot‐assisted radical prostatectomy, androgen deprivation therapy, and radiotherapy. Case presentation A 73‐year‐old man with a prostate‐specific antigen level of 4.3 ng/mL was diagnosed with prostate cancer. Following the robot‐assisted radical prostatectomy, the pathological diagnosis was mucinous adenocarcinoma of the prostate (pT3bpN0, Gleason score of 4 + 4). Salvage hormonal therapy and irradiation were performed after the prostatectomy. Enlargement of the left testis was noted, and 28 months after prostatectomy, computed tomography detected a left testicular tumor and nodular lesions in the bilateral lungs. The histopathological diagnosis of left high orchiectomy was metastasis of a mucinous adenocarcinoma of the prostate. Chemotherapy with docetaxel followed by cabazitaxel was initiated. Conclusion Mucinous prostate adenocarcinoma with distal metastases following prostatectomy has been managed for longer than 3 years with multiple treatments.

Abstract Background Since the human papillomavirus vaccines do not eliminate preexisting infections, nonsurgical alternative approaches to cervical intraepithelial neoplasia (CIN) have been required. We previously reported that FOXP4 (forkhead box transcription factor P4) promoted proliferation and inhibited squamous differentiation of CIN1‐derived W12 cells. Since it was reported that FOXP expressions were regulated by the androgen/androgen receptor (AR) complex and AR was expressed on the CIN lesions, in this study we examined the effects of androgen on CIN progression. Methods Since AR expression was negative in W12 cells and HaCaT cells, a human male skin‐derived keratinocyte cell line, we transfected AR to these cell lines and investigated the effects of dihydrotestosterone (DHT) on their proliferation and squamous differentiation. We also examined the immunohistochemical expression of AR in CIN lesions. Results DHT reduced the intranuclear expression of FOXP4, attenuating cell proliferation and promoting squamous differentiation in AR‐transfected W12 cells. Si‐RNA treatments showed that DHT induced the expression of squamous differentiation‐related genes in AR‐transfected W12 cells via an ELF3‐dependent pathway. DHT also reduced FOXP4 expression in AR‐transfected HaCaT cells. An immunohistochemical study showed that AR was expressed in the basal to parabasal layers of the normal cervical epithelium. In CIN1 and 2 lesions, AR was detected in atypical squamous cells, whereas AR expression had almost disappeared in the CIN3 lesion and was not detected in SCC, suggesting that androgens do not act to promote squamous differentiation in the late stages of CIN. Conclusion Androgen is a novel factor that regulates squamous differentiation in the early stage of CIN, providing a new strategy for nonsurgical and hormone‐induced differentiation therapy against CIN1 and CIN2.

Abstract Carboplatin plus etoposide is a standard treatment for older extensive‐stage small‐cell lung cancer (ES‐SCLC) patients with performance status (PS) 2. However, older patients often exhibit poor PS (3, 4), and the treatment effect in them is poorly understood. To determine the therapeutic efficacy and safety of carboplatin plus etoposide therapy for this population, we retrospectively analyzed 63 patients with ES‐SCLC with PS ≥2, aged ≥71 years, who had received first‐line carboplatin plus etoposide therapy. We compared the treatment efficacy and safety in patients with baseline PS 2 versus those with PS 3–4. In the PS 2 (38 patients) and PS ≥3 (25 patients) groups, the overall response rate was 71.1% and 72.0%, median progression‐free survival was 4.6 and 3.1 months, and overall survival was 7.7 and 5.1 months, respectively. PS improved to 0–1 post‐treatment in 65.8% and 48.0% of the patients in the PS 2 and PS ≥3 groups, respectively. Patients with PS ≥3 showing improved PS had a progression‐free survival of 6.1 months. A higher incidence of grade ≥3 decreased neutrophil counts, febrile neutropenia, and treatment‐related death was observed in the PS ≥3 group. The progression‐free survival of patients administered prophylactic granulocyte colony‐stimulating factor (G‐CSF) was 5.2 and 6.1 months in the PS2 and PS ≥3 groups. Overall, carboplatin plus etoposide therapy provided comparable tumor shrinkage, but shorter progression‐free and overall survival in older ES‐SCLC patients with PS ≥3 than in those with PS 2. Thus, supportive care, such as prophylactic G‐CSF administration, may be necessary to ensure safety and survival.

Abstract Background Programmed cell death 1 (PD‐1)/programmed cell death ligand (PD‐L1) inhibitors plus chemotherapy (ICI + Chemo) is the standard treatment for advanced non‐small‐cell lung cancer (NSCLC). However, the impact of tumour burden on the efficacy of ICI + Chemo remains unknown. Methods We retrospectively evaluated 92 patients with advanced NSCLC treated with ICI + Chemo. Tumour burden was assessed as the sum of the longest diameter of the target lesion (BSLD) and number of metastatic lesions (BNMLs). We categorised the patients into three groups based on the combined BSLD and BNML values. Results Sixty‐eight patients (74%) had progressive disease or died. Forty‐four patients (48%) in the low‐BSLD group had a median progression‐free survival (PFS) of 9.5 months, whereas patients in the high‐BSLD group had a median PFS of 4.6 months (hazard ratio [HR] = 0.54, p = 0012). Twenty‐five patients (27%) in the low‐BNML group had a median PFS of 9.6 months, whereas patients in the high‐BNML group had a median PFS of 6.5 months (HR = 0.51, p = 0.029). Low‐BSLD and low‐BNML were associated independently with improved PFS in multivariate analysis. Analysis of the tumour burden combined with BSLD and BNML revealed a trend towards improved PFS as the tumour burden decreased, with median PFS of 22.3, 8.7, and 3.9 months in the low‐ (N = 13), medium‐ (N = 42) and high‐burden (N = 37) groups respectively. Conclusions Our findings demonstrated that a high tumour burden negatively impacts the efficacy of ICI + Chemo in patients with advanced NSCLC.

Introduction Testicular ectopia refers to abnormal positioning of testis, which includes a wide variety of variants. An ectopic testis is located off the normal path of male gonadal descent, unlike conventional undescended testis. Case presentation A 37‐year‐old man presented with the complaint of a palpable lesion in the scrotum. Magnetic resonance imaging of the scrotum revealed bilateral testes on the respective opposite sides of the scrotum with bilateral spermatic cords crossing under the base of the penis. Accordingly, he was diagnosed as “left‐right reversal of the testes within the scrotum.” In retrospect, the “palpable” lesion was thought to be the spermatic cords crossing above the testes. Semen analysis identified deteriorated sperm motility, suggesting possible male infertility. Conclusion This case of left–right reversal of the testes within the scrotum is probably a new variant of testicular ectopia that has never been reported.

Introduction Sepsis with concomitant acute pyelonephritis, secondary to urolithiasis, is common. We report a case of sepsis‐induced cardiomyopathy with acute pyelonephritis, successfully managed with venoarterial extracorporeal membrane oxygenation. Case presentation A 64‐year‐old woman presented with fever and disturbed consciousness. Abdominal computed tomography revealed right hydronephrosis with ipsilateral ureteral stone. Despite ureteral stent placement and antibiotic treatment, her hemodynamics worsened. She was diagnosed with sepsis‐induced cardiomyopathy and underwent venoarterial extracorporeal membrane oxygenation. Her hemodynamics improved rapidly; venoarterial extracorporeal membrane oxygenation was withdrawn on postoperative day‐3. She was discharged from our hospital after sufficient antibiotic treatment. Conclusion Venoarterial extracorporeal membrane oxygenation may be initiated in patients with sepsis‐induced cardiomyopathy. Evaluation of left ventricular ejection fraction via echocardiography is important to determine the indication for venoarterial extracorporeal membrane oxygenation.

Abstract Objective Sporadic inclusion body myositis (sIBM) is the most common acquired myopathy in patients older than 50 years of age. sIBM is hardly responds to any immunosuppressing theraphies, and its pathophysiology remains elusive. This study aims to explore pathogenic pathways underlying sIBM and identify novel therapeutic targets using metabolomic and transcriptomic analyses. Methods In this retrospective observational study, we analyzed biopsied muscle samples from 14 sIBM patients and six non‐diseased subjects to identify metabolic profiles. Frozen muscle samples were used to measure metabolites with cation and anion modes of capillary electrophoresis time of flight mass spectrometry. We validated the metabolic pathway altered in muscles of sIBM patients through RNA sequencing and histopathological studies. Results A total of 198 metabolites were identified. Metabolomic and transcriptomic analyses identified specific metabolite changes in sIBM muscle samples. The pathways of histamine biosynthesis and certain glycosaminoglycan biosynthesis were upregulated in sIBM patients, whereas those of carnitine metabolism and creatine metabolism were downregulated. Histopathological examination showed infiltration of mast cells and deposition of chondroitin sulfate in skeletal muscle samples, supporting the results of metabolomic and transcriptomic analyses. Interpretation We identified alterations of several metabolic pathways in muscle samples of sIBM patients. These results suggest that mast cells, chondroitin sulfate biosynthesis, carnitine, and creatine play roles in sIBM pathophysiology.

Introduction We report two cases of mesh migration into the bladder after inguinal hernia surgery. Case presentation In the first case, a 48‐year‐old woman who underwent right internal inguinal hernia repair, 18 months prior, presented with pollakiuria and microscopic hematuria that was resistant to antibiotics. A submucosal tumor was detected at the bladder dome by cystoscopy, and transurethral resection was performed. Intraoperatively, a migrated mesh was observed in the submucosal lesion. In the second case, a 55‐year‐old man who underwent a right external inguinal hernia repair, approximately 14 years prior, presented with persistent microscopic hematuria and pyuria. Cystoscopy revealed mesh migration to the upper right bladder wall. Both patients underwent partial cystectomy with mesh removal, and their complaints were resolved after surgery. Conclusion Mesh migration should be suspected in patients with a history of inguinal hernia repair, accompanied by persistent lower urinary tract symptoms or abnormal urinalysis findings.

Introduction Signet‐ring cell carcinoma is an extremely rare histological variant of upper urinary tract carcinoma, associated with poor prognosis. Case presentation We report a case of a 75‐year‐old female diagnosed with left primary upper urinary tract signet‐ring cell carcinoma, initially treated with surgery. Post‐surgical development of multifocal metastases was followed by a devastating clinical course. An autopsy confirmed the tumor's primary origin in the upper urinary tract. Conclusion We experienced a case of upper urinary tract signet‐ring cell carcinoma, with a rare opportunity to thoroughly confirm its primary site with an autopsy.

Abstract Background Cancer cachexia and tumor burden predict efficacies of programmed cell death‐1 (PD‐1)/programmed death‐ligand 1 (PD‐L1) inhibitors and chemotherapy or pembrolizumab in non‐small cell lung cancer (NSCLC). There are no predictive models that simultaneously assess cancer cachexia and tumor burden. Methods In the present retrospective study, we reviewed the medical records of patients with advanced NSCLC who received cancer immunotherapy as first‐line systemic therapy. Clinical immune predictive scores were defined according to multivariate analysis of progression‐free survival (PFS) and overall survival (OS). Results A total of 157 patients were included in the present study (75 treated with PD‐1/PD‐L1 inhibitors + chemotherapy; 82, pembrolizumab monotherapy). Multivariate analysis for PFS revealed that PD‐L1 tumor proportion scores

Introduction Intravascular large B‐cell lymphoma is a rare and aggressive type of extranodal large B‐cell lymphoma. Although intravascular large B‐cell lymphoma can invade various organs, renal involvement has been rarely reported. Synchronous occurrence of intravascular lymphoma with renal cell carcinoma is extremely rare. We herein report a case of intravascular large B‐cell lymphoma in a renal cell carcinoma incidentally detected by robot‐assisted partial nephrectomy. Case presentation A 69‐year‐old female with recurrent fever lasting 4 years underwent robot‐assisted partial nephrectomy for small renal cell carcinoma. Histological findings led to the diagnosis of intravascular large B‐cell lymphoma, which involved the normal tissue of right kidney as well as clear cell renal cell carcinoma. She received six cycles of chemotherapy without major complications and achieved complete remission. Conclusion We encountered a rare case of synchronous intravascular lymphoma with renal cell carcinoma.

Abstract Background Adipose tissue induces inflammation, which desensitizes the efficacy of immunotherapy. However, several reports show that the therapeutic effect of programed cell death 1 (PD‐1)/programed death‐ligand 1 (PD‐L1) inhibitor(s) monotherapy is significantly better in obese patients. Therefore, the effect of adipose tissue on immunotherapy is unclear. Methods In this study, we retrospectively reviewed patients with advanced non‐small cell lung cancer (NSCLC) who received PD‐1/PD‐L1 inhibitor monotherapy between May 2016 and December 2018. We classified patients into total adipose tissue maintenance or loss groups according to adipose tissue change during the 6 months before treatment and compared the therapeutic effect of PD‐1/PD‐L1 inhibitors between these groups along with the presence or absence of cachexia, a poor prognostic factor. Results Of the 74 patients, 40 (54.1%) were cachexic. Among cachexic patients, we found no clear difference in the overall response rate (ORR) and progression‐free survival (PFS) between the total adipose tissue maintenance and loss group. However, among noncachexic patients, the total adipose tissue loss group had a higher ORR (64.7% vs. 23.5%, p

Abstract Background Coronavirus disease 2019 (COVID‐19) is known to cause not only respiratory but also neuropsychiatric symptoms, which are assumed to be derived from a cytokine storm and its effects on the central nervous systems. Patients with COVID‐19 who develop severe respiratory symptoms are known to show severe neuropsychiatric symptoms such as cerebrovascular disease and encephalopathy. However, the detailed clinical courses of patients with neuropsychiatric symptoms caused by mild or asymptomatic COVID‐19 remain poorly understood. Here, we present a case of COVID‐19 who presented with severe and prolonged neuropsychiatric symptoms subsequent to mild respiratory symptoms. Case presentation A 55‐year‐old female with COVID‐19 accompanied by mild respiratory symptoms showed delusion, psychomotor excitement, and poor communication ability during quarantine outside the hospital. Considering her diminished respiratory symptoms, her neuropsychiatric symptoms were initially regarded as psychogenic reactions. However, as she showed progressive disturbance of consciousness accompanied by an abnormal electroencephalogram, she was diagnosed with post‐COVID‐19 encephalopathy. Although her impaired consciousness and elevated cytokine level improved after steroid pulse therapy, several neuropsychiatric symptoms, including a loss of concentration, unsteadiness while walking, and fatigue, remained. Conclusions This case suggests the importance of both recognizing that even apparently mild COVID‐19‐related respiratory symptoms can lead to severe and persistent neuropsychiatric symptoms, and elucidating the mechanisms, treatment, and long‐term course of COVID‐19‐related neuropsychiatric symptoms in the future.

Abstract Background Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs) are currently the primary treatment option for patients with EGFR‐mutant non‐small cell lung cancer (NSCLC). However, the effect of EGFR‐TKIs are eventually weakened due to resistance, and there is also a differential efficacy based on EGFR mutation subtypes. The combination of angiogenesis inhibitor (AI) with EGFR‐TKI has shown better efficacy than EGFR‐TKI monotherapy, regardless of the mutation subtypes. Nevertheless, the effect of AI eligibility on overall survival (OS) and progression‐free survival (PFS) remains to be elucidated. Thus, we assessed this impact on patients with NSCLC harboring EGFR mutation. Methods In this study, the data for 450 patients with EGFR‐mutant NSCLC, who were treated with EGFR‐TKI monotherapy, were retrospectively analyzed for AI eligibility. The patients were categorized into AI‐eligible (AI fit) and ineligible groups (AI unfit). Results The median PFS of the AI fit group was 12.9 months, compared to 9.6 months in the unfit group (p = 0.007), and OS was also significantly longer in the AI fit group (median OS = 33.0 months) compared to that in the unfit group (18.5 months, p

Introduction Intravesical Bacillus Calmette–Guerin immunotherapy is known to prevent recurrence of bladder cancer, but it can cause tuberculosis infections as an adverse event. Case presentation A 75‐year‐old man visited our hospital due to hematuria. The patient was diagnosed with bladder cancer and underwent transurethral resection of the bladder tumor. Postoperatively, the patient received Bacillus Calmette–Guerin immunotherapy. One year later, we performed transurethral surgery and prostate biopsy because of cystoscopic findings showing nodulous lesions in the bladder and an elevated serum prostate‐specific antigen level. The patient presented with high fever and malaise since the surgery. After careful examination, the patient was diagnosed with miliary tuberculosis caused by Mycobacterium bovis. The pathology of the bladder and prostate revealed acid‐fast bacilli collection by Ziehl–Neelsen staining. Conclusion The surgery exacerbated the local infection into a systemic infection. The risk of developing miliary tuberculosis should be considered at transurethral surgery or prostate biopsy in patients after intravesical Bacillus Calmette–Guerin immunotherapy.

Introduction The development of secondary tumors is a well‐known late adverse event after urinary diversion. However, the frequency of secondary tumors after an ileal conduit is the lowest compared to other methods used for urinary diversion. We observed a rare case of a gastrointestinal stromal tumor in an ileal conduit detected by recurrent massive bleeding from the stoma. Case presentation An 87‐year‐old female was hospitalized at our hospital due to recurrent bleeding from a stoma 22 years after radical cystectomy. Contrast‐enhanced computed tomography revealed a 5‐cm mass in her ileal conduit. She underwent a complete resection of the tumor, a histological examination of which revealed it to be a gastrointestinal stromal tumor. The condition of the patient has been good showing no recurrence or metastases 4 years after surgery. Conclusion We report a rare secondary tumor, a gastrointestinal stromal tumor, arising from an ileal conduit.

Abstract Programmed cell death ligand‐1 (PD‐L1) is a ligand for programmed cell death‐1 (PD‐1) that negatively regulates T‐cell activation and plays a crucial role in suppressing anti‐tumor host immunity. Although PD‐L1 is a promising immunotherapy target in various cancers, including urothelial carcinoma (UC), the prognostic significance of PD‐L1 in UC is unclear. As platelets help protect tumor cells from immune elimination in the circulatory system, we hypothesized that tumor PD‐L1 and circulating platelets might synergistically promote tumor metastasis, and that the prognostic significance of PD‐L1 might vary according to platelet count. We immunohistochemically examined tumor PD‐L1 expression in 271 patients with upper tract UC, which revealed PD‐L1 positivity in 31 of 271 cases (11%). The associations of tumor PD‐L1 expression with outcomes varied among patients with high or low platelet counts (Pinteraction

Introduction Myxoid liposarcoma tends to be a relatively good prognosis. Follow‐up is recommended once a year from the 5th year after surgery. Case presentation A 48‐year‐old man had a massive retroperitoneal tumor, measuring approximately 20 cm. Resection of a huge myxoid liposarcoma had been performed on his back 10 years ago and the weight of the mass was 14 kg. The tumor was resected from the right kidney and its weight was 3.6 kg. Pathological examination showed myxoid liposarcoma and therefore, the tumor was diagnosed as recurrent. But after the resection, no recurrence or metastasis was observed. Conclusion To our knowledge, the case presents the first report where both initial and recurrent tumors were massive and the time for recurrence was 10 years. Therefore, a follow‐up of myxoid liposarcoma might have to be done cautiously throughout the patient's life.

Novel hydrophilic sulfur-containing adsorbents for noble metals were prepared by the radical terpolymerization of a methacrylate bearing dithiocarbonate moieties (DTCMMA), hydrophilic monomers, and a cross-linker. The resulting adsorbents efficiently and selectively adsorbed noble metals (Au, Ag, and Pd) from various multielement aqueous solutions at room temperature owing to the thiocarbonyl group having high affinity toward noble metals. The metal adsorption by the adsorbents was proceeded by simple mixing followed by filtration. The noble metal selectivity of the adsorbent obtained from DTCMMA and N-isopropylacrylamide was higher than that of the adsorbent obtained from DTCMMA and N,N-dimethylacrylamide due to the lower nonspecific adsorption.

Despite the recent development of immunosuppressive agents, plasma cell-rich acute rejection (PCAR) has remained refractory to treatment. Herein, we report an unusual case of PCAR that responded well to pulse steroid therapy alone. A 47-year-old man was admitted for a protocol biopsy three months after kidney transplantation, with a stable serum creatinine level of 1.6 mg/dL. Histological examination showed focal aggressive tubulointerstitial inflammatory cell infiltration of predominantly polyclonal mature plasma cells, leading to our diagnosis of PCAR. Three months following three consecutive days of high-dose methylprednisolone (mPSL) therapy, an allograft biopsy performed for therapy evaluation showed persistent PCAR. We readministered mPSL therapy and successfully resolved the PCAR. Although PCAR generally develops more than six months after transplantation, we diagnosed this case early, at three months after transplantation, with focally infiltrated PCAR. This case demonstrates the importance of early diagnosis and prompt treatment of PCAR to manage the development and severity of allograft rejection.

Ureterosigmoidostomy is associated with the risk of several late complications including cancer development at anastomotic sites. We present an unusual case with adenocarcinoma of the anastomotic site associated with multiple adenocarcinoma lesions in the upper urinary tract. A 69-year-old man complained of persistent melena and hematuria. He had undergone radical cystectomy for high-grade bladder cancer and ureterosigmoidostomy 30 years before. Colonoscopy showed a tumor at the right ureterocolonic anastomosis, which was endoscopically resected and histologically diagnosed as adenocarcinoma. Seven years later, a tumor of the left ureterocolonic anastomosis associated with hydronephrosis was found. He underwent temporal percutaneous nephrostomy followed by sigmoidectomy and left ureterocutaneostomy. Eighteen months after the operation, computed tomography (CT) detected left renal pelvic tumor with a mass along the former nephrostomy tract. Left nephroureterectomy and resection of the nephrostomy tract tumor revealed adenocarcinoma with multiple lesions of adenocarcinoma in the ureter. These tumors showed atypical immunohistochemistry as a colonic adenocarcinoma: positive for cytokeratin 7, negative for cytokeratin 20, and negative for β-catenin nuclear accumulation. Anastomotic site adenocarcinoma of the present case is potentially of urothelial origin because of unusual clinical manifestation and immunohistochemistry as a colon cancer.

A 46-year-old man, who had visited our hospital complaining of a small intrascrotal nodule ten years ago, returned to us because of the rapid growth of the nodule. Computed tomography revealed a heterogeneously enhanced intrascrotal tumor of approximately 4×3 cm. The tumor and the right testis were excised with the adhered right scrotal skin. The pathological diagnosis was pleomorphic leiomyosarcoma with dedifferentiation originating from the dartos muscle. Urological dedifferentiated leiomyosarcomas are rarely reported and the clinical features are mostly unknown. This is the first report to describe the dedifferentiated leiomyosarcoma of the dartos muscle.

We describe an unusual case of renal cell carcinoma (RCC) involving the entire upper urinary tract. A 51-year-old female was referred to us because of macroscopic hematuria. Computed tomography revealed a renal tumor filling renal pelvis and ureter, which turned to be a clear cell RCC after nephroureterectomy.

Nephrotic syndrome, after administration of tyrosine kinase inhibitors, is uncommon and not well known. A 62-year-old male, who had experienced a left nephrectomy due to a traffic accident 38 years ago, underwent a partial nephrectomy for right renal cell carcinoma (RCC). Histologically, the tumor was a clear cell RCC. Two years later abdominal CT revealed para-aortic lymph node metastasis. During these two years, serum creatinine had increased from 2.0 mg/dL to 2.9 mg/dL along with the appearance of proteinuria. After only a week of sorafenib, 400 mg/day, fever developed and sorafenib was stopped. Although normotensive, his serum creatinine increased to 3.83 mg/dL and serum albumin decreased from 1.8 g/L to 1.0 g/L. Proteinuria also worsened to 27.5 g/day. He became edematous, and ascites and cardiac effusions also appeared. He was diagnosed with nephrotic syndrome. A retrospective review of the histology of the partial nephrectomy revealed no change in the glomeruli.

Background: Certain dietary patterns can elicit systemic and intestinal inflammatory responses, which may influence adaptive anti-tumor immune responses and tumor behavior. We hypothesized that pro-inflammatory diets might be associated with higher colorectal cancer mortality and that the association might be stronger for tumors with lower immune responses., Methods: We calculated an empirical dietary inflammatory pattern (EDIP) score in 2829 patients among 3988 incident rectal and colon carcinoma cases in the Nurses' Health Study and Health Professionals Follow-up Study. Using Cox proportional hazards regression analyses, we examined the prognostic association of EDIP scores and whether it might be modified by histopathologic immune reaction (in 1192 patients with available data)., Results: Higher EDIP scores after colorectal cancer diagnosis were associated with worse survival, with multivariable-adjusted hazard ratios (HRs) for the highest versus lowest tertile of 1.41 (95% confidence interval [CI]: 1.13-1.77; P trend = 0.003) for 5-year colorectal cancer-specific mortality and 1.44 (95% CI, 1.19-1.74; P trend = 0.0004) for 5-year all-cause mortality. The association of post-diagnosis EDIP scores with 5-year colorectal cancer-specific mortality differed by degrees of tumor-infiltrating lymphocytes (TIL; P interaction = .002) but not by three other lymphocytic reaction patterns. The multivariable-adjusted, 5-year colorectal cancer-specific mortality HRs for the highest versus lowest EDIP tertile were 1.59 (95% CI: 1.01-2.53) in TIL-absent/low cases and 0.48 (95% CI: 0.16-1.48) in TIL-intermediate/high cases., Conclusions: Pro-inflammatory diets after colorectal cancer diagnosis were associated with increased mortality, particularly in patients with absent or low TIL., (© 2022 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

Background: Plant-based foods have been recommended for health. However, not all plant foods are healthy, and little is known about the association between plant-based diets and specific molecular subtypes of colorectal cancer (CRC). We examined the associations of healthy and unhealthy plant-based diets with the incidence of CRC and its molecular subtypes., Methods: While 123 773 participants of the Nurses' Health Study and the Health Professionals Follow-up Study had been followed up (3 143 158 person-years), 3077 of them had developed CRC. Healthy and unhealthy plant-based diet indices (hPDI and uPDI, respectively) were calculated using repeated food frequency questionnaire data. We determined the tumoural status of microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and BRAF and KRAS mutations., Results: Higher hPDI was associated with lower CRC incidence (multivariable hazard ratio [HR] comparing extreme quartiles, 0.86, 95% confidence interval [CI]: 0.77, 0.96; P-trend = .04), whereas higher uPDI was associated with higher CRC incidence (multivariable HR comparing extreme quartiles, 1.16, 95% CI: 1.04, 1.29; P-trend = .005). The association of hPDI significantly differed by KRAS status (P-heterogeneity = .003) but not by other tumour markers. The hPDI was associated with lower incidence of KRAS-wildtype CRC (multivariable HR comparing extreme quartiles, 0.74, 95% CI: 0.57, 0.96; P-trend = .004) but not KRAS-mutant CRC (P-trend = .22)., Conclusions: While unhealthy plant-based diet enriched with refined grains and sugar is associated with higher CRC incidence, healthy plant-based diet rich in whole grains, fruits and vegetables is associated with lower incidence of CRC, especially KRAS-wildtype CRC., (© 2022 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

Background: The C-reactive protein to albumin (CRP/Alb) ratio, a novel inflammation-based prognostic score, is associated with outcomes in septic patients. The prognostic value of CRP/Alb ratio has not been established in cancer patients. The aim of this study is to evaluate the significance of CRP/Alb ratio in therapeutic outcome after pancreatic resection for pancreatic cancer., Methods: The study comprised 113 patients who had undergone pancreatic resection for pancreatic cancer between April 2001 and December 2011. We retrospectively investigated the relation between CRP/Alb ratio and disease-free as well as overall survival., Results: The optimal cut-off level of the CRP/Alb ratio was 0.03. For disease-free survival, preoperative biliary drainage (p = 0.011), advanced tumor-node-metastasis (TNM) classification (p = 0.002), and higher CRP/Alb ratio (p = 0.049) by univariate analysis, and advanced TNM classification (p = 0.003) by multivariate analysis, were independent and significant predictors of cancer recurrence. For overall survival, preoperative biliary drainage (p = 0.012), advanced TNM classification (p = 0.001), and higher CRP/Alb ratio (p = 0.023) by univariate analysis, and advanced TNM classification (p = 0.003) and higher CRP/Alb ratio (p = 0.035) by multivariate analysis, were independent and significant predictors of poor patient outcome., Conclusions: The CRP/Alb ratio may be an independent and significant indicator of poor long-term outcomes in patients with pancreatic cancer after pancreatic resection.

Background: Systemic inflammation as evidenced by the Glasgow prognostic score (GPS) predicts cancer-specific survival in various types of cancer. The aim of this study was to evaluate the significance of GPS in therapeutic outcome after surgical resection of gallbladder cancer., Methods: The subjects were 51 patients who underwent surgical resection for gallbladder cancer. For the assessment of systemic inflammatory response using the GPS, patients were classified into three groups: patients with normal albumin (≥3.5 g/dl) and normal C-reactive protein (CRP) (≤1.0 mg/dl) as GPS 0 (n = 38), those with low albumin (<3.5 g/dl) or elevated CRP (>1.0 mg/dl) as GPS 1 (n = 8), and those with low albumin (<3.5 g/dl) and elevated CRP (>1.0 mg/dl) as GPS 2 (n = 5). We retrospectively investigated the relation between patient characteristics including GPS, and disease-free as well as overall survival., Results: In disease-free survival, advanced tumor stage based on pathology (p = 0.006), positive lymph node metastasis (p = 0.001), and GPS 1 or 2 (p = 0.006) were independent predictors of cancer recurrence in multivariate analysis. In overall survival, positive lymph node metastasis (p = 0.002) and GPS 1 or 2 (p = 0.032) were independent predictors of poor patient outcome in multivariate analyses., Conclusion: The GPS in patients with gallbladder cancer is an independent prognostic predictor after surgical resection.