Treatment with trastuzumab deruxtecan in patients with HER2-positive breast cancer and brain metastases and/or leptomeningeal disease (ROSET-BM).

Therapeutic options for breast cancer patients with brain metastases (BM)/leptomeningeal carcinomatosis (LMC) are limited. Here, we report on the effectiveness and safety of trastuzumab deruxtecan (T-DXd) in human epidermal growth factor receptor 2-positive breast cancer patients with BM. Data were analyzed for 104 patients administered T-DXd. Overall response rate (ORR), progression-free survival (PFS), overall survival (OS), intracranial (IC)-ORR, and IC-PFS were evaluated. ORR by investigator assessment was 55.7% (total population). Median PFS was 16.1 months; 12-month OS rate was 74.9% (total population). Median time-to-treatment failure was 9.7 months. In 51 patients with BM imaging, IC-ORR and median IC-PFS by independent central review were 62.7% and 16.1 months, respectively. In 19 LMC patients, 12-month PFS and OS rates were 60.7% and 87.1%, respectively. T-DXd showed effectiveness regarding IC-ORR, IC-PFS, PFS, and OS in breast cancer patients with BM/active BM, and sustained systemic and central nervous system disease control in LMC patients.Trial Registration: UMIN000044995.

[Urethrocutaneous Fistula Caused by a Vesical Foreign Body in an Adolescent Boy : A Case Report].

In daily medical practice, we occasionally encounter patients with a foreign body in the urinary bladder. However, the identification of such a foreign body in an adolescent and the occurrence of an urethrocutaneous fistula caused by the foreign body are extremely rare. Only two cases have been reported previously. Herein we present a case of a foreign body in the urinary bladder and an urethrocutaneous fistula in a young patient. A 14-year-old boy with fever, left scrotal pain and urinary incontinence was referred to our department. Intravenous pyelography and micturition cystourethrography findings revealed a vesical foreign body and an urethrocutaneous fistula. He mentioned that he had inserted two dozen magnets into the urethra for masturbation one year previously. As the foreign bodies were spherical small magnets, we performed transurethral surgery and successfully removed the magnets. His postoperative course was uneventful and he was discharged from our department on the seventh day after surgery. Three months following surgery, the fistula had closed spontaneously.

[A Case Report : Primary Urothelial Carcinoma of the Prostate Producing Interleukin-6 Detected from a Fever].

A 72-year-old man visited a hospital because of a fever and fatigue. His fever persisted and computed tomography revealed a tumor of the prostate. The patient was referred to our hospital with a suspicion of prostate cancer. The blood test showed increased serum C-reactive protein (CRP) level without any infectious findings. Tumor markers including prostate specific antigen were within the normal range and urine cytology was negative. Prostate needle biopsy revealed urothelial carcinoma. No tumor was detected in other areas of the urinary tract. Therefore we diagnosed the patient with primary urothelial carcinoma of the prostate, cT3N0M0. Serum interleukin-6 (IL-6) elevated up to 68 ng/ml. We were not able to detect any metastatic lesions and performed radical cystoprostatectomy and ileal conduit. Serum CRP and IL-6 levels decreased and the fever declined. There has been no relapse 52 months after the surgery.

[Vesical Perforation Caused by a Foreign Body : A Case Report --A Clinical Review of 41 Cases in Japan-].

In daily medical practice, we occasionally encounter a foreign body present in the urinary bladder. However, the occurrence of vesical perforation caused by a foreign body is rare. A 53-year-old man with vesical pain and macrohematuria was referred to our department because of the presence of a foreign body in his urinary bladder. He seemed to have inserted the foreign body from the urethra during use of a stimulant drug according to his story. Cystoscopy revealed that the plastic foreign body had a few barbs and had penetrated the bladder through the left lateral wall. On performing computed tomography, we did not detect any injuries to other organs or hematoma formation. Therefore, we performed elective suprapubic cystostomy and removed the plastic foreign body. The patient's postoperative course was favorable, and he left our department on the sixth day after surgery.

[A Case of Clear Cell Adenocarcinoma Arising from a Female Urethral Diverticulum].

Adenocarcinoma arising from the female urethral diverticulum is very rare, as only about 100 cases have been reported worldwide. An 82-year-old woman presented with asymptomatic macrohematuria. A transvaginal examination revealed a firm circular mass on the anterior vaginal wall. Cystourethroscopy showed a urethral tumor, which was determined to be clear cell adenocarcinoma after transurethral resection of the urethral tumor. However, we could not resect all of the tumor, so anterior pelvic exenteration and ileal conduit urinary diversion were performed. The final pathological diagnosis was clear cell adenocarcinoma arising from the urethral diverticulum. However multiple lymph node metastases appeared 10 months after surgery. The patient refused additional therapy and died 23 months after surgery.

[A CASE REPORT: LITHIASIS OF THE LEFT ECTOPIC PELVIC KIDNEY].

We report a case of lithiasis of the left ectopic pelvic kidney. A 70-year-old man was admitted to our department for left lower back pain. He has been aware of gross hematuria since three or four years before. Computed tomography demonstrated the left ectopic pelvic kidney with a 16-mm stone and a 5-mm stone in the renal pelvis which was accompanied by hydronephrosis. Ten days later, the renal pelvic stones moved to the renal calices and the symptoms disappeared. Though a pyeloureteral junction obstruction was not evident, renogram showed a obstruction pattern of the left kidney. He had been followed up for six years, then the stone was impacted in the renal pelvis and hydronephrosis worsened. Open pyelolithotomy was performed. His clinical course was uneventful and no evidence of recurrence has been observed.

[Penile Tuberculosis : A Case Report].

A 66-year-old man presented with a chief complaint of glans penis pain, induration, and discharge of pus. He was prescribed a course of antibiotics, but the condition persisted despite treatment. Thus, we differrentially diagnosed the patient with penile tuberculosis and pyoderma gangrenosum, and performed a biopsy of the penis. The biopsy result was thickening of the horny layer epidermis with only a foreign body granuloma composed of inflammatory cells, and did not lead to a definitive diagnosis. Thoraca-abdominal computed tomography revealed axillary lymphadenopathy with necrosis. Suspecting tuberculosis lymphadenitis, we performed T-spot and QuantiFERONtests. The result was T-spot negative and QuantiFERONpositive, so we diagnosed the patient with penile tuberculosis, and started antituberculosis medication. In about half a year after the start of treatment the symptoms subsided, and lymphadenopathy showed reduction.

[Solitary Fibrous Tumor in the Retroperitoneum : A Case Report].

A 55-year-old man was diagnosed with an abdominal tumor and referred to our department. Abdominal contrast-enhanced computed tomography revealed a 15-cm tumor in the retroperitoneum. The inferior vena cava was compressed ventrally, the right ureter laterally, and the right kidney toward the head. Part of the tumor was situated on the dorsal side of the abdominal aorta. A preoperative diagnosis of neurogenic tumor or a type of sarcoma was made. We performed en bloc resection of the tumor. The right kidney was also resected. We exfoliated between the tumor and inferior vena cava without temporary interruption. The final diagnosis was a solitary fibrous tumor. The patient received no adjuvant therapy. Neither recurrence nor metastasis has been detected for 8 months postoperatively.

[A case of giant testicular tumor in a schizophrenic patient].

A 55-year-old man with schizophrenia presented with right scrotal enlargement. Clinical examination revealed a right adult -head-sized testicular tumor, multiple lymph node metastasis with marked elevation of serum lactic dehydrogenase (LDH) and ß -human chorionic gonadotropin (ß -HCG). Right high orchiectomy followed by chemotherapy with bleomysin, etoposide and cisplatin (BEP) for 4 cycles was performed. The tumor weighed 5,270 g, and was pathologically diagnosed as seminoma. After the treatment, the tumor markers were normalized, but he refused to undergo retroperitoneal lymph node dissection.

[Castleman's disease of the kidney: a case report].

Castleman's disease is a rare disorder characterized by benign proliferation of lymphoid tissue. A 61-year-old man was referred to our department for a renal mass incidentally detected by magnetic resonance imaging. Computed tomography showed a 18 × 20 × 14 mm mass in the upper pole of the right kidney, which enhanced at the early phase and washed out at the late phase. On the diagnosis of renal cell carcinoma, laparoscopic partial nephrectomy was performed. Pathological examinations revealed a hyaline-vascular type of Castleman's disease confined to the kidney.

[Panhypopituitarism caused by an intrasellar cystic mass in late-onset hypogonadism clinic].

A 74-year-old man who was referred to our late onset hypogonadism clinic presented with sweating and loss of appetite. His aging males' symptoms (AMS) and international index of erectile function (IIEF-5) scores were 59 and 2, respectively. His hormonal examination revealed extremely low free testosterone values. The patient was started on androgen replacement therapy, but his symptoms did not improve. Additional hormonal examinations revealed low values for other anterior pituitary hormones. Magnetic resonance imaging revealed an intrasellar cystic mass with suprasellar extension. We considered this mass caused hypothalamic hypopituitarism. A load test for anterior pituitary hormones revealed panhypogonadism. His symptoms improved after administration of adrenal and thyroid hormones and androgen. Five months after start of drug administration, his AMS score improved to 29, but IIEF-5 score showed little change. As a matter of course, not only androgen but all pituitary-related hormones are needed for hypopituitarism patients.

[Primary adenocarcinoma of the seminal vesicle difficult to differentiate from rectal carcinoma : a case report].

A 78-year-old man with urinary retention visited our hospital in June 2011. He presented with intestinal bleeding one month later and was admitted immediately. Contrast enhancement computed tomography revealed a lobulated intrapelvic tumor and liver metastasis. The prostate specific antigen level was normal, but his carcinoembryonic antigen level was elevated. Based on these results, his tumor was diagnosed as rectal carcinoma. On day 26, total pelvic exenteration and pelvic lymph node dissection to arrest bleeding were performed. We created an ileal conduit for urinary diversion and performed a sigmoid colostomy. The final histopathological assessment confirmed that he had primary adenocarcinoma of the seminal vesicle. The patient received the best supportive care because he rejected postoperative adjuvant chemotherapy and hormonal therapy. He died three months postoperatively. Primary adenocarcinoma of the seminal vesicle is very rare. The prognosis for this carcinoma is poor.

[Poor outcome due to spontaneous rupture of renal cell carcinoma : a case report].

A 54-year-old man experienced sudden onset of severe pain in his left lower back. Because the pain persisted for two days, he visited our hospital. Abdominal computed tomography revealed a hematoma around his left kidney, which was diagnosed as spontaneous rupture of a renal tumor. He was immediately admitted and was scheduled to undergo elective surgery. However, because his hemoglobin level decreased suddenly on Day 9 and rebleeding from the renal tumor was suspected, we chose to perform left radical nephrectomy following emergency transcatheter arterial embolization of his left renal artery. The resected specimen was a solid brownish-red mass surrounded by hematoma, and the histopathological findings revealed that it was a renal clear cell carcinoma (G3＞G2, INFα, pT1b, and pV0). On Day 51, he was found to have a local recurrence of carcinoma, and died five months after surgery. Spontaneous rupture of renal cell carcinoma is relatively rare : this is the 104th report on surgery for this carcinoma in Japan.

[A case of metabolic acidosis and tetany after ileal neobladder replacement].

A 64-year-old man visited our hospital with the complaint of macrohematuria and bilateral hydronephrosis. He had undergone total cystectomy and ileal neobladder replacement under the diagnosis of muscle invasive bladder cancer (cT2bN0M0). Tetany due to hyperventilation syndrome appeared on postoperative day 42. Blood gas analysis showed metabolic acidosis (pH 7.260, pO2 148.1 mmHg, pCO2 20.7 mmHg, HCO3 9.1 mmHg, BE -16.0 mmol/l). His condition was immediately improved after a urethral catheter was placed and sodium bicarbonate was administered. After re-removal of the urethral catheter, however, hyperventilation syndrome recurred. He was discharged from the hospital with the urethral catheter placed.

[IgG4-related idiopathic segmental ureteritis which was difficult to distinguish from ureteral cancer: a case report].

A 79-year-old woman was admitted with a chief complaint of gross hematuria, pollakisuria, lower abdominal pain. Urine cytology, intravenous pyelography, and cystoscopy were performed but showed no abnormal findings. About 6 months later, abdominal computed tomography (CT) revealed a 5cm long segment of ureteral narrowing with wall thickening, hydronephrosis, para-aortic lymph node swelling. Retrogradepyelography (RP) was done. Pelvic urine cytology was class IV. Under the clinical diagnosis of ureteral carcinoma and lymph node metastasis, a left nephroureterectomy with lymph node dissection was performed. The pathological diagnosis was IgG4-related idiopathic segmental ureteritis.

[A case of bladder cancer with metastasis to the bone of the hand].

Metastasis to the bone of the hand is rare. In addition, metastasis to the bone of the hand from bladder cancer is extremely rare. We herein report a case of distal phalanx metastasis from bladder cancer. A 64- year-old man who was diagnosed with bladder cancer (cT2bN0M0) received total cystectomy (pT3bN2). Two months after the surgery, a roentgenogram revealed lung metastasis. Then we administered 2 cycles of chemotherapy using gemcitabine and cisplatin. Computed tomography revealed a partial response. However, several months after chemotherapy, we noted that his left ring finger was swollen and showed erythema. We made a diagnosis of metastasis to the distal phalanx of the left ring finger and amputated the finger. Pathological findings showed no conflict with metastasis from bladder cancer. Postoperative course was good, but he died about three months after the diagnosis of metastasis.

[Successful treatment of spontaneous rupture of pheochromocytoma with laparoscopic adrenalectomy: a case report].

A 46-year-old man had sudden onset of severe left hypochondrial pain and went into shock following hospitalization. Computed tomography, echocardiography, and endocrinological tests revealed spontaneous rupture of a pheochromocytoma associated with catecholamine cardiomyopathy. After he underwent conservative management with fluid replacement, his blood pressure stabilized and cardiac function improved. Twenty-two days later, he was referred to our hospital. After admission, as his circulatory dynamics was stable, we performed elective laparoscopic left adrenalectomy. He was discharged on the tenth postoperative day. Spontaneous rupture of a pheochromocytoma is very rare : laparoscopic surgery for this condition has been reported only on 2 previous occasions worldwide.

[Three cases of penile self-mutilation].

Penile self-mutilation is rare. We report our experience with 3 cases of penile self-amputation. One case was in a 48-year-old man who had no background history of mental disorders. He amputated his penis using a utility knife. He was referred to our hospital and underwent suture of the wound, but he took his own life one week after the surgery. Another case was in a 42-year-old man who had intelligence impairment. He amputated his penis using a kitchen knife. The other case was in a 41-year-old man who had schizophrenia. He amputated his penis using a piece of broken glass.

[Successful testicular sperm extraction in a non-obstructive azoospermic man with severe testicular microlithiasis : a case report].

A 45-year-old man was referred to our hospital for treatment of azoospermia. On physical examination, right testicular volume was 2 ml, left testicular volume was 3 ml, and pubic Tanner stage was 5. Scrotal ultrasonography revealed a high echoic lesion with acoustic shadowing at surfaces of bilateral testes. Semen analysis showed azoospermia and serum follicle stimulating hormone value was high (28.42 mIU/ml). He was diagnosed with non-obstructive azoospermia, and underwent microdissection testicular sperm extraction. Both testes were filled with shiny granular materials. In excised tissue of the testes, seminiferous tubules containing spermatozoa were found and motile spermatozoa were successfully retrieved. The histological examination revealed many small calcifications which had laminated structure. Spermatogenesis was slightly impaired, and Johnsen's score count was 9. Testicular microlithiasis has been reported to be an infrequent condition associated with conditions such as testicular tumors and testicular dysgenesis syndrome. Such a severe testicular microlithiasis has not been reported previously.

Adenovirus-mediated gene transfer of triple human complement regulating proteins (DAF, MCP and CD59) in the xenogeneic porcine-to-human transplantation model. Part II: xenogeneic perfusion of the porcine liver in vivo.

In this study, the adenovirus-mediated gene transfer of triple human complement regulating proteins was investigated in xenogeneic pig liver perfusion. The porcine liver was perfused in situ at 4 degrees C under a pump-driven veno-venous shunt of the portal vein and inferior vena cava, with 5 to 15x10(11) plaque-forming units (pfu) of adenovirus vector (group 1: AxCALacZ; 2: AxCACD59; 3: AxCACD59 + AxCADAF; 4: AxCACD59 + AxCADAF + AxCAMCP) for 1 h (for each, n=3). The livers were harvested 24 h after gene transfer and then were reperfused ex-vivo with fresh human blood for 2 h. In immunohistochemical staining, each complement regulating protein (CRP) showed a distribution similar to that of the LacZ expression. The C3 levels in the perfusate were also maintained at higher levels in group 4 from 60 to 120 min after reperfusion (C3: 85% to 95% of the initial level) than in groups 1 to 3 (C3: 80% to 90% of the initial level) from 60 to 120 min after reperfusion. The complement deposition on the porcine liver [C3, membrane attack component (MAC)] decreased significantly more in group 4 than in groups 1 to 3. In conclusion, the adenovirus-mediated multiple gene transfer of human CRPs (hCRPs) was found to effectively suppress the complement activation in xenogeneic pig liver perfusion.