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BackgroundThe study aimed to examine the significance of insulin receptor (INSR) expression in predicting resistance to axitinib in clear cell renal cell carcinoma (ccRCC).MethodsClinicopathological data were collected from 36 consecutive patients with metastatic RCC who received axitinib. Thirty-three primary tumours were obtained for immunohistochemistry. Patient-derived xenograft (PDX) models were created by transplanting primary tumours into immunodeficient mice, establishing axitinib-resistant PDX models. RCC cell lines were co-cultured with human renal glomerular endothelial cells (HGECs) treated with siRNA of INSR (HGEC-siINSR). Gene expression alteration was analysed using microarray.ResultsThe patients with low INSR expression who received axitinib had a poorer outcome. Multivariate analysis showed that INSR expression was the independent predictor of progression-free survival. INSR expression decreased in axitinib-resistant PDX tumours. RCC cell lines showed upregulated interferon responses and highly increased interferon-β levels by co-culturing with HGEC-siINSR. HGECs showed decreased INSR and increased interferon-β after axitinib administration. RCC cell lines co-cultured with HGEC-siINSR showed high programmed death-ligand 1 (PD-L1) expression, which increased after interferon-β administration.ConclusionsDecreased INSR in RCC could be a biomarker to predict axitinib resistance. Regarding the resistant mechanism, vascular endothelial cells with decreased INSR in RCC may secrete interferon-β and induce PD-L1.

Introduction Vaginal complications following radical cystectomy may require surgical treatment. We herein report a case of successful laparoscopically assisted vulvar reconstruction using the gluteal fold flap for anterior enterocele following robot‐assisted radical cystectomy. Case presentation A 71‐year‐old Japanese woman underwent robot‐assisted radical cystectomy for bladder cancer (ypT1ypN1M0). The bladder, urethra, bilateral ovaries, and anterior vaginal wall were removed together transvaginally. The Mercedes‐Benz closure technique was performed for vaginal reconstruction using the posterior vaginal wall. Seventeen months after surgery, she complained of a vulvar bulge, and physical examination confirmed a tennis ball‐sized anterior enterocele. Therefore, she underwent laparoscopically assisted vulvar reconstruction using the gluteal fold flap. No recurrence had developed at 6 months postoperatively. Conclusion The combination with laparoscopy allows vulvar reconstruction to be performed safely and efficiently.

Background/Aim: Intermediate-risk prostate cancer (PCa) is a highly heterogeneous disease. Although low-dose-rate brachytherapy (LDR-BT) is mainly used for low- to intermediate-risk PCa, limited reports have evaluated the detailed differences in outcomes, including differences between patients with ISUP grade group (GG) 2 and GG3 intermediate-risk PCa. This study aimed to investigate the differences in outcomes between intermediate-risk Japanese patients with GG2 and GG3 PCa who underwent LDR-BT. Patients and Methods: This single-center retrospective study included 342 consecutive patients with intermediate-risk PCa; 232 patients with GG2 and 110 with GG3 were treated with LDR-BT at Tokushima University Hospital between July 2004 and December 2019. Results: No significant difference in 5-year biochemical progression-free survival and cancer-specific survival was observed between patients with GG2 and those with GG3 (p=0.649 and p=0.633, respectively). Multivariate analysis showed that radiation doses up to 90% of the prostate volume (D90) and the percentage of positive cores were predictors of recurrence in all patients with intermediate-risk PCa. Group analyses showed that D90 was a predictor for recurrence in patients with GG2. In contrast, a high percentage of positive cores was a significant risk factor for recurrence in patients with GG3. Conclusion: Positive core ratios observed on prostate biopsy correlated with higher recurrence rates after LDR-BT. This indicates that the proportion of positive cores in the biopsy may be an important factor in predicting the likelihood of recurrence, especially for patients with GG3 PCa.

Introduction Congenital diaphragmatic hernia (CDH) can result in intrathoracic displacement of the kidney, presenting anatomical challenges for robot‐assisted radical nephrectomy (RARN). Reports of RARN in such cases are scarce. Case Presentation A 56‐year‐old man with a history of right‐sided CDH repair was referred for evaluation of an incidentally discovered right renal mass. Computed tomography revealed two right renal tumors (cT1aN0M0) and cranial displacement of the kidney into the thoracic cavity. Given the possibility of intra‐abdominal adhesions and the retrohepatic location of the kidney, retroperitoneal RARN was selected. An intercostal trocar was used to access the high‐positioned kidney. The renal vessels were safely managed using a Vas Guide, and no complications occurred. Pathology confirmed clear cell renal cell carcinoma (pT1aN0M0). Conclusion RARN can be safely performed in patients with prior CDH repair and intrathoracic renal displacement. Preoperative planning and alternative trocar strategies, such as intercostal placement, are essential for successful outcomes.

Background Robot-assisted radical cystectomy (RARC) and intracorporeal urinary diversion are less invasive than conventional procedures. However, for older patients, cutaneous ureterostomy (CUS) may be preferred because urinary diversion using the intestine has a high incidence of perioperative complications and is highly invasive. The purpose of this study was to demonstrate the safety and efficacy of intracorporeal ileal conduit (ICIC) compared with CUS in patients aged 75 years or older who underwent RARC. Methods From October 2014 to December 2021, 82 patients aged 75 years or older who underwent RARC at Tokushima University Hospital, Tokushima Prefectural Central Hospital, or Ehime Prefectural Central Hospital were retrospectively reviewed. Of these, 52 and 25 patients who underwent ICIC and CUS, respectively, were included. After adjusting the patients’ characteristics using propensity score-matching, surgical results and prognoses were retrospectively compared. The propensity score was based on age, Eastern Cooperative Oncology Group Performance Status Scale (ECOG-PS), American Society of Anesthesiologists physical status classification (ASA-PS), clinical tumor stage, and neoadjuvant chemotherapy. Results The median age was lower in the ICIC group compared with the CUS group, and the proportion of high-risk cases (ECOG-PS ≥ 2 or ASA-PS ≥ 3) did not differ. The median operation time was longer in the ICIC group, and estimated blood loss was higher, compared with the CUS group. There were no significant differences in the incidence of complications within the first 30 postoperative days, incidence of complications 30–90 days after surgery, 2-year overall survival, 2-year cancer-specific survival, and 2-year recurrence-free survival. The stent-free rate was significantly lower in the CUS group than that in the ICIC group. Conclusion In older patients, the ICIC group showed non-inferior surgical and oncological outcomes compared with the CUS group. Urinary diversion following RARC in older patients should be carefully selected by considering not only the age but also the general condition (including comorbidities) of the patient.

The influence of the console surgeon on the feasibility and outcome of various robot-assisted surgeries has been evaluated. These variables may be partially affected by the skills of the patient-side surgeon (PSS), but this has not been evaluated using objective data. This study aimed to describe the surgical techniques of the PSS in robot-assisted radical cystectomy (RARC) and intracorporeal ileal conduit (ICIC) urinary diversion and objectively examine the changes in surgical outcomes with increasing PSS experience. During a 3-year period, 28 men underwent RARC and ICIC urinary diversion. Clinical characteristics and surgical outcomes were compared between patients who underwent surgery early (first half group) or late in the study period (second half group). The pre-docking incision enabled easy specimen removal. The glove port technique widened the working space of the PSS. The stay suture allowed the PSS to control the distal portion of the conduit, facilitating the passage of the ureteral stents. During stoma creation, pneumoperitoneum pressure was lost by opening the abdominal cavity. To overcome this problem, the robotic arm was used to lift the abdominal wall to maintain the surgical field and facilitate the PSS procedure. Compared with the first half group, the second half group had significantly shorter times for urinary diversion (202 min vs 148 min, p  < 0.001), ileal isolation and anastomosis (73 min vs 45 min, p  < 0.001), and stenting (23.0 min vs 6.5 min, p  < 0.001). As the experience of the PSS increased, the time of the PSS procedures decreased.

This study was performed to clarify the therapeutic and diagnostic roles of lymph node dissection (LND) by examining the impact of LND and lymph node yield (LNY) on oncological outcomes in patients undergoing robot-assisted radical cystectomy (RARC). Between 2014 and 2021, 216 patients underwent LND during RARC at Tokushima University Hospital and affiliated hospitals. Among the 216 patients, we compared 115 patients with an LNY of ≥ 20 and 101 with an LNY of < 20 to investigate the impact of LNY on surgical and oncological outcomes. Furthermore, we investigated the impact of LNY and the extent of LND on oncological outcomes by dividing the extent of LND into two groups (standard and extended). The 3-year rates of overall survival (OS) ( p  = 0.256), cancer-specific survival (CSS) ( p  = 0.791), and recurrence-free survival (RFS) ( p  = 0.953) did not differ between the two groups divided by the LNY. A higher LNY was associated with a significantly higher lymph node positivity rate ( p  = 0.020). The incidence of LND-related major complications was not significantly different between the two groups ( p  = 0.910). The 3-year survival rates did not differ between the two groups divided by the extent of LND: OS ( p  = 0.366), CSS ( p  = 0.814), and RFS ( p  = 0.689). The LNY and extent of LND were not associated with oncological outcomes in patients undergoing LND during RARC, whereas a higher LNY was associated with lymph node positivity. In the era of adjuvant therapy with immune checkpoint inhibitors, LND during RARC has an important diagnostic role in the detection of pathological node positivity.

Introduction Leptomeningeal carcinomatosis in small cell carcinoma of the prostate is rare. Case presentation A 69‐year‐old man visited our hospital due to dysuria and edema. Bilateral hydronephrosis and lymph node metastases due to a pelvic tumor were observed. Although the prostate‐specific antigen level was normal, the tumor was suspected to originate from the prostate. He underwent percutaneous nephrostomy and prostate biopsy. Histopathology revealed small cell carcinoma accompanied by increased pro‐gastrin‐releasing peptide and neuron‐specific enolase levels. After receiving systemic chemotherapy with carboplatin and etoposide and radiation therapy for prostate, these lesions gradually decreased in size, and tumor markers normalized. Ten months after the initial diagnosis, he developed consciousness disorder and seizure. Magnetic resonance imaging revealed leptomeningeal carcinomatosis without any other recurrences and elevated tumor markers. He died 4 weeks after these symptoms appeared. Conclusion Careful monitoring of the central nervous system should be considered in small cell carcinoma of the prostate patients.

Introduction A case of multiple liver metastases of clear cell RCC with a significant response to sunitinib as the fifth line after nivolumab is reported. Case presentation The patient was a 65‐year‐old man who underwent open nephrectomy for RCC. After the nephrectomy, he had recurrences several times, and metastasectomy had been performed for each recurrence. At 13 years after the nephrectomy, multiple liver, and lung metastases appeared. The treatment was switched to axitinib, followed by cabozantinib, then nivolumab. The best response was PR, SD, and PD for these three drugs, and treatment duration was 14, 3, and 3 months, respectively. As the fifth line, sunitinib was administered, with significant shrinkage of the multiple liver metastases, and PR has been maintained for 34 months. Conclusion Sunitinib after an IO‐drug showed a significant effect in spite of only slight efficacy with other VEGFR‐TKIs, which may have occurred through the alteration of the immunological microenvironment.

Introduction Granulocyte colony‐stimulating factor‐producing nonhematopoietic malignancies have poor clinical outcomes. Case presentation A 62‐year‐old woman complaining of fever and left lower quadrant pain was referred to our hospital. A left retroperitoneal tumor was suspected on computed tomography, and laboratory data showed leukocytosis and markedly elevated granulocyte colony‐stimulating factor. She underwent left nephroureterectomy, partial colectomy, and psoas muscle resection. The histological examination showed a granulocyte colony‐stimulating factor‐producing retroperitoneal leiomyosarcoma. Three months after the operation, she developed lung and liver metastases and received the chemotherapy, including doxorubicin and ifosfamide. Eight months after the operation, these lesions had progressed, and a new bone metastasis appeared. Twelve months after the operation, she received pazopanib and radiation for bone metastases. However, the metastases progressed, and she died 17 months after the operation. Conclusion Since granulocyte colony‐stimulating factor‐producing retroperitoneal leiomyosarcoma had a very poor prognosis irrespective of intensive treatment including wide resection, effective systemic therapy should be required.