Published papers

Postoperative femoral nerve palsy (FNP) is a rare complication associated with urologic surgery. Inappropriate use of retractors, use of lithotomy position, and prolonged surgery that lead to the femoral nerve compression have been reported as risk factors for FNP. Here, we report two cases of FNP after pelvic surgery. Case 1: A 47-year-old woman underwent ureterocystoneostomy for a giant ureterocele. On the first postoperative day, she developed muscle weakness and paresthesia in the left lower leg. An orthopedic surgeon diagnosed her with FNP associated with the surgery. Case 2: An 82-year-old woman underwent radical cystectomy for invasive bladder cancer. On the second postoperative day, she developed extension deficit in the left lower leg and was diagnosed with an iatrogenic FNP. Although this complication is infrequent, at onset, it leads to difficulty in walking and gait disturbance in the patient. As a result, it greatly reduces the patient's postoperative quality of life. Therefore, preventive measures should be taken to reduce the risk of this postsurgical nerve injury, such as appropriate placement of retractors and proper patient positioning during the operation.

Magnetic resonance imaging (MRI) ultrasound fusion biopsy is becoming popular owing to the better detection rate of clinically significant prostate cancer (csPCa). We retrospectively evaluated the accuracy of MRI-targeted biopsy during the period of introduction at a single academic center by comparing findings of its specimen and whole-mount histopathology. Between June 2018 and January 2021, 106 transperineal MRI-ultrasound fusion biopsies using BioJet software were performed. Among the cases, 15 subsequently underwent robotic-assisted laparoscopic radical prostatectomy and were eligible for analysis. This study included all regions of interest (ROIs) with a Prostate Imaging Reporting and Data System v2 category of 3 or greater on pre-biopsy MRI．For each lesion, grade group of MRI-targeted biopsy specimens and prostatectomy specimens were compared. From a total of 25 ROIs identified among 15 males, csPCa was found in 21 (84%) of the concordant locations of prostatectomy specimens. However, MRI-targeted biopsy could diagnose csPCa in only 12 (48%) of them. In the csPCa undetected group, the ROI volume was significantly smaller (median volume 0.23 ml vs 0.40 ml, p＝0.03). We also found that in cases where PCa was not detected through MRI-targeted biopsy, the biopsy sample length was significantly shorter (median length 9 mm vs 17 mm, p＝0.01). Our data suggest that failure of detecting PCa in MRI-targeted biopsy could be due to technical errors at the introduction period of the technique. A sufficient sampling length of 10 mm or more is desirable, especially for small lesions.

We retrospectively analyzed the effect of lymph node dissection (LND) in patients with renal cell carcinoma (RCC). Of 151 patients who underwent nephrectomy for RCC, 86 underwent LND. No distant metastasis (M0) was present in 71 patients, although distant metastasis (M1) was present in 15. Three (4.2%) and eight (53%) patients in the M0 and M1 groups, respectively, were clinical N-stage positive. Two (2.8%) and three (20%) patients in the M0 and M1 groups, respectively, were pathological N-stage positive. Both pathological N stage-positive patients in the M0 group were pathologically diagnosed with microphthalmia transcription family translocation RCC. The clinical and pathological positive node areas exhibited concordance in all three pathological N stage-positive patients in the M1 group. Chylous leakage occurred in 16 (19%) patients in the LND group (p＜0.05). Extended LND was a statistically significant risk factor for chylous leakage in the multivariate analysis. Only limited cases should undergo LND, owing to the low frequency of positive pathological lymph node metastasis, and high complication rate.

A man in his 60s was diagnosed with clear cell carcinoma of the right kidney with multiple lung metastases, tumor thrombus of the inferior vena cava (IVC), and invasion of the duodenum and pancreas. Ipilimumab plus nivolumab was administered as first-line therapy. After 3 treatment courses, computed tomography (CT) demonstrated a slight decrease in the size of the primary tumor and lung metastases. However, the patient became hemodynamically unstable due to persistent duodenal bleeding during treatment despite frequent blood transfusions. Axitinib was then initiated as second-line therapy. The duodenal bleeding ceased 10 days after starting axitinib and his anemia remissed. Subsequent CT showed further decrease in the size of the primary tumor and lung metastases. The patient underwent right nephrectomy after improvement of nutrition. IVC thrombectomy, and pancreaticoduodenectomy. The lung metastases disappeared on postoperative imaging and no additional treatment was provided. Twelve months after surgery, he was in good health and showed no signs of recurrence.

A 22-year-old woman was referred to our hospital for further examination of an incidentally discovered hypervascular pelvic tumor with a maximum diameter of 10 cm. Although Castleman disease was suspected based on the imaging findings and pathologic findings of the needle biopsy, a definitive diagnosis was not made. Preoperative transcatheter arterial embolization was performed to decrease intraoperative bleeding, and tumor resection was performed on the following day. As for posterior approach prior to anterior approach, the patient was placed in a prone position, and the dorsal aspect of tumor was approached through the dissection of gluteal muscles. Then, dilated branches of the internal iliac vein was found on the tumor capsule, which were safely ligated under direct vision with favorable visual field. Then, the patient was placed in a supine position, the tumor was completely resected by anterior approach without transfusion. Histopathological diagnosis was Castleman disease hyaline vascular type. The patient was discharged without complication and has been free from recurrence for 6 months after surgery.

Case 1 : A 75-year-old man was emergently admitted to our hospital with a complaint of continuous bleeding from the ileal conduit. The conduit was constructed by a total pelvic resection for sigmoid colon cancer that invaded the urinary bladder 24 years ago. Swollen cutaneous mucosa was seen around the ileal conduit, but no obvious bleeding spot was observed. The contrast-enhanced computed tomographic (CT) scan and 3D visualization revealed varices extending to the abdominal wall. Percutaneous transhepatic embolization successfully stopped the bleeding, but it was needed again after two years. Case 2 : A 72-yearold man with a history of open cystectomy and ileal conduit for bladder cancer came to our hospital two years after the surgery, complaining of continuous bleeding from the conduit. The skin around the stoma site was discolored purple, but no obvious bleeding site or bloody urine was observed. The CT scan similar to Case 1 revealed varices in the ileal conduit, and percutaneous transhepatic embolization successfully stopped the bleeding, but it was needed again after five months. After that, three months passed without recurrence.

Background: Evidence suggests neurotransmitter signaling may play a crucial role in tumorigenesis of gastrointestinal (GI) cancers, including migration, proliferation, and apoptosis, as well as angiogenesis and the microenvironment. We developed and applied a strategy to identify upstream regulators of neurotransmitters and their associations with patient outcomes. Methods: Prior literature yielded 85 neurotransmitter signaling genes mapped to RNA-seq gene expression in tumor tissue from 545 patients with mCRC enrolled in the phase III CALGB/SWOG 80405 trial. These samples were also sequenced by FoundationOne CDx for DNA damage. Using Cox proportional hazards regression, we identified a subset of CDx genes associated with overall survival (OS) or progression-free survival (PFS). We extended the Causal Inference Test (CIT) for time-to-event data and identified a subset of the 85 signaling genes consistent with mediation of DNA mutation effects on OS and PFS. Another CIT analysis identified potential upstream neurotransmitter regulators, gene expression mediators of mutation effects on the signaling genes. Top genes were then assessed in whole-transcriptome sequencing (WTS) expression data with Caris MI profile collected from 398 patients with advanced CRC enrolled in the MONSTAR-SCREEN-2 trial. Results: At the 0.05 alpha level, we identified 20 signaling genes with gene expression associated with PFS and/or OS, and 68 genes with evidence of DNA mutations associated with PFS and/or OS. False discovery rate (FDR) < 0.05 was applied to filter the 56,674 expression features on PFS and OS associations, yielding 173 unique genes as possible mediators. The CIT yielded 53 putative mediators at FDR < 0.05, suggesting upstream regulation of neurotransmitter signaling. Five genes were identified as targeting at least 8 signaling genes each, PIGU, ANO9, LY6G6D, and GPR160, and FSCN1, where the first 4 are favorable and only FSCN1 is a poorer prognostic. Following up on these 5 genes in MONSTAR-SCREEN-2 by dichotomizing at the median value of WTS expression, 3 were nominally associated with OS, PIGU (P = 0.050; HR, 0.59; 95%CI, 0.34-1.00), ANO9(P = 0.029; HR, 0.55; 95%CI, 0.32-0.95), LY6G6D(P = 0.0024; HR, 0.44; 95%CI, 0.25-0.76), and FSCN1 was suggestive (P = 0.079; HR, 1.62; 95%CI, 0.94-2.77), with direction of effects in agreement with 80405 results for all four. Conclusions: Our novel approach identified previously unknown upstream regulators of neurotransmitter signaling associated with treatment outcomes in mCRC. PIGU, FSCN1, and LY6G6D have been suggested in prior literature as targets for CRC and ANO9 has been suggested as a target for GI cancer. These results bolster the strategy of using mediation analysis with large-scale molecular data to identify new therapeutic targets in CRC. NCT00265850.