副腎性クッシング症候群におけるゲノム解析

学位の種別: 課程博士審査委員会委員 : (主査)東京大学教授 南学 正臣, 東京大学准教授 福原 浩, 東京大学特任教授 井川 靖彦, 東京大学講師 須並 英二, 東京大学講師 森川 鉄平University of Tokyo(東京大学

Influence of lifestyle choices on risks of CYP1B1 polymorphisms for prostate cancer.

Cytochrome P450 1B1 (CYP1B1) converts xenobiotics to carcinogens and how lifestyle choices may interact with CYP1B1 polymorphisms and affect prostate cancer risk was assessed. Blood genomic DNA from a Caucasian population was analysed at polymorphic sites of the 5' untranslated region of CYP1B1 using TaqMan genotyping assays. Overall, drinker status and minor alleles at rs2551188, rs2567206 and rs10175368 were associated with prostate cancer. Linkage was observed between rs2551188, rs2567206, rs2567207 and rs10175368, and the G-C-T-G haplotype (major allele at respective sites) was decreased in cancer. Interestingly when classified by lifestyle factors, no associations of genotypes were found for non-smokers and non-drinkers, whereas on the contrary, minor type at rs2567206 and rs10175368 increased and major G-C-T-G decreased risk for cancer among smokers and drinkers. Interestingly, rs2551188, rs2567206 and rs10175368 minor genotypes correlated with increased tissue CYP1B1 as determined by immunohistochemistry. Further, rs10175368 enhanced luciferase activity and mobility shift show stronger binding of nuclear factor for the minor allele. These results demonstrate smoking and alcohol consumption to modify the risks of CYP1B1 polymorphisms for prostate cancer which may be through rs10175368, and this is of importance in understanding their role in the pathogenesis and as a biomarker for this disease

Parenchymal renal rupture due to an obstructive ureteric calculus in an incompletely duplicated renal pelvis and ureter

Introduction Parenchymal renal rupture due to a ureteric calculus is extremely rare and an emergency. Case presentation A 54‐year‐old man was brought to the emergency room with left back pain without trauma. Computed tomography showed left parenchymal renal rupture with an incompletely duplicated renal pelvis, ureter, and an 11‐mm ureteric calculus in the ureterovesical junction. A ureteral stent was placed, and the patient was treated conservatively as his vital signs were stable. We performed transurethral lithotripsy after resolution of the perirenal hematoma. Conclusion To best of our knowledge, this report is the first to present a case of parenchymal renal rupture due to a ureteric calculus in an incompletely duplicated renal pelvis and ureter. Ureteric calculus within an incompletely duplicated renal pelvis and ureter is at risk of parenchymal renal rupture. Therefore, the aggressive treatment of ureteric calculus could be important

A case of mid‐ureteral stricture with ipsilateral atrophic kidney in a young adult

Introduction Most congenital ureteral strictures occur at the ureteropelvic or ureterovesical junction in children. Mid‐ureteral stricture is very rare and can cause congenital hydronephrosis. Only a few studies have reported on coexisting mid‐ureteral stricture with ipsilateral atrophic kidney in young adults. Case presentation A 16‐year‐old girl presented with repeated urinary tract infection. Computed tomography revealed a right atrophic kidney and hydroureter. Retrograde pyelography showed a mid‐ureteral stricture. Laparoscopic nephroureterectomy was performed, and histological examination revealed mid‐ureteral stricture with hyperplasia of the fibrous connective tissue and an atrophic kidney. Conclusion Mid‐ureteral stricture in a young adult is extremely rare. Appropriate imaging studies including retrograde pyelography are necessary for accurate diagnosis of mid‐ureteral stricture

A case of severe ureteral injury repaired by renal autotransplantation with an iliac vein patch using bovine pericardium

Introduction Renal autotransplantation is considered a surgical procedure for extensive ureteral defects. Herein, we report a case of severe ureteral injury repaired by laparoscopic nephrectomy and renal autotransplantation with an iliac vein patch using bovine pericardium. Case presentation A 56‐year‐old woman who had previously undergone gynecological surgery complained of right‐sided abdominal pain. She was then later diagnosed with a right middle ureteral injury with a 5‐cm long defect. We performed retroperitoneal laparoscopic nephrectomy and renal autotransplantation. As the iliac vein was fragile, venous patching using bovine pericardium was performed. The patient's renal function was well preserved after surgery. Conclusion Laparoscopic nephrectomy and renal autotransplantation is an effective method for repairing severe ureteral injury with the preservation of renal function. A venous patch using bovine pericardium might be considered as a replacement for a fragile vein

Two cases of pelvic hematoma after prostatic urethral lift surgery

Introduction There are few reports of pelvic hematoma after prostatic urethral lift. Here, we report two cases of pelvic hematoma in Japan. Case presentation The first case was a 71‐year‐old man with benign prostatic hyperplasia who underwent prostatic urethral lift. Although the procedure was uneventful, he experienced lower abdominal pain the day after the operation. CT revealed a hematoma in the right pelvis; however, it was manageable with conservative treatment. The second case was a 68‐year‐old man. The procedure was uneventful; however, 6 days after the operation, a subcutaneous hematoma appeared in the lower abdomen. CT revealed a hematoma in the left pelvis. We then performed pelvic hematoma removal surgery. Conclusions Pelvic hematomas after PUL may requires attention, particularly in men with the narrow pelvises. Appropriate compression of the prostate and a high lithotomy position procedure could effectively avoid the occurrence of pelvic hematomas

Metastatic bladder cancer forming a sigmoidorectal fistula after enfortumab vedotin therapy: a case report

We report the case of a 68-year-old man who developed a sigmoidorectal fistula after marked response to enfortumab vedotin for advanced bladder cancer. The patient had undergone radical cystectomy with ileal conduit after neoadjuvant chemotherapy. Six months after surgery, local recurrence in the pelvic cavity and multiple lung metastases were found, and the patient was administered pembrolizumab as second-line therapy. Due to worsening local recurrence and suspected invasion of the sigmoid colon and rectum, enfortumab vedotin was initiated as third-line therapy and comprehensive genomic profiling was simultaneously performed. Enfortumab vedotin was remarkably effective, the lung metastases disappeared, and the local recurrent lesion shrank in volume although a sigmoidorectal fistula was found to form through the tumor cavity. Immunohistochemical analysis of the tumor specimens exhibited increased nectin-4 expression. This rare case of metastatic bladder cancer with sigmoidorectal fistula associated with effective enfortumab vedotin therapy suggests that nectin-4 expression and comprehensive genomic profiling might be useful in predicting treatment response to enfortumab vedotin

A case of complete response to avelumab plus axitinib combination therapy for metastatic clear cell renal cell carcinoma in a kidney undergoing dialysis

Introduction Combination therapies of immune checkpoint and tyrosine kinase inhibitors for end‐stage kidney disease and patients on hemodialysis need careful consideration as few case reports provide suitable management decisions. Case presentation A 70‐year‐old man who had undergone hemodialysis for 6 years due to nephrosclerosis. Avelumab plus axitinib combination therapy was performed for repeated lung metastasis, and a complete response was achieved without major side effects. Conclusion A complete response was achieved after Ave plus Axi combination therapy for clear cell renal cell carcinoma in a patient undergoing dialysis. This suggests that Ave plus Axi combination therapy may be safe and effective for dialysis patients