Clinical utility of intraductal carcinoma of the prostate in treatment selection for metastatic hormone-sensitive prostate cancer.

BACKGROUND: In recent years, the usefulness of androgen receptor axis-targeted agents (ARATs) such as abiraterone, enzalutamide, and apalutamide for the upfront treatment of metastatic hormone-sensitive prostate cancer (mHSPC) has been demonstrated. However, it remains unclear which patients would truly benefit from these treatments. Furthermore, intraductal carcinoma of the prostate (IDC-P) is a known poor prognostic factor in patients with prostate cancer. We investigated the association between the presence of IDC-P and response to therapy in patients with mHSPC. METHODS: This retrospective analysis included 318 patients with mHSPC who received treatment at Nagoya University and its 12 affiliated institutions between 2014 and 2021. Their biopsy specimens were evaluated for the presence of IDC-P. The patients were classified according to their first-line treatment into the ARAT (n = 100, receiving a combination of androgen-deprivation therapy [ADT] and ARAT) or conventional therapy (n = 218, receiving ADT with or without standard antiandrogen agents) group. We compared the overall survival (OS) and second progression-free survival (PFS2) between the ARAT and conventional groups according to the presence of IDC-P to evaluate whether presence of IDC-P predicts the response to each treatment. PFS2 was defined as the period from mHSPC diagnosis to disease progression on second-line treatment or death. Propensity score matching with one-to-one nearest-neighbor matching was used to minimize the potential effects of selection bias and confounding factors. The clinicopathological variables of the patients were well-balanced after propensity score matching. RESULTS: Most patients in the ARAT (79%) and conventional therapy (71%) groups were ICD-P positive. In the propensity score-matched cohort, the OS and PFS2 of IDC-P-positive patients were significantly longer in the ARAT group than in the conventional group (OS: hazard ratio [HR], 0.36; p = 0.047; PFS2: HR, 0.30; p < 0.001). In contrast, no difference in OS and PFS2 was observed between the ARAT and conventional groups in IDC-P-negative patients (OS: HR, 1.09; p = 0.920; PFS2: HR, 0.40; p = 0.264). CONCLUSIONS: The findings highlight a high prevalence of IDC-P among patients with mHSPC and suggest that IDC-P positivity may be a reliable indicator that ARAT should be implemented as first-line treatment.

Gain-switched pulse generation of 5.3†ps from 30†GHz-modulation-bandwidth 1270†nm DFB laser diode.

We generated gain-switched pulses via electrical pulse excitations in a 1270 nm distributed feedback (DFB) laser diode (LD) with a direct-modulation bandwidth of 30 GHz. The measurements revealed short-pulse widths of 5.3 and 8.8 ps with and without chirp compensation, via a single-mode optical fiber. The 5.3 ps pulses exhibited a spectral width of 0.40 nm (spectral bandwidth of 71 GHz), yielding a time-bandwidth product of 0.38. Although the gain-switched pulses in DFB LDs inherently contain linear and nonlinear chirp, optimized pumping conditions enable generation of nearly transform-limited ps pulses after linear chirp compensation.

Fast-frame single-shot pump-probe spectroscopy with chirped-fiber Bragg gratings.

To acquire single-shot pump-probe waveforms for each laser pulse at a high repetition rate and high signal-to-noise ratio, we combined the photonic time-stretch technique and time-encoding method using a chirped-fiber Bragg grating (CFBG) and a grating-pair pulse compressor. By changing the pre-chirping of the probe pulse, a variable time window of the pump-probe traces from 1.4 to 17 ps was demonstrated. The use of a CFBG improved the signal-to-noise ratio of the waveforms by minimizing the loss of probe pulses due to the transmission through a long fiber. These techniques are promising, for example, in applications in multi-timescale pump-probe spectroscopy of irreversible phenomena.

[A Case of Synchronous Malignant Pheochromocytomas in Bilateral Adrenal Glands].

We present a case of synchronous malignant pheochromocytoma in bilateral adrenal glands. A 73- year-old man presented to our hospital with bilateral adrenal masses incidentally found during abdominal ultrasonography examination for an unrelated issue. The patient had a 30-year history of hypertension and paroxysmal atrial fibrillation. Computed tomography and magnetic resonance imaging showed heterogeneous tumors in bilateral adrenal glands and an enlarged para-aortic lymph node. Hormonal examinations revealed a high value of urinary catecholamines. Metaiodobenzylguanidine (MIBG) scintigraphy showed increased uptake in bilateral adrenal glands and the lymph node. Both adrenal tumors and the node were surgically removed. Pathological examination revealed histologically distinct tissue between the two adrenal tumors. The patient received five cycles of adjuvant chemotherapy, consisting of cyclophosphamide, vincristine, and dacarbazine. The patient has been in remission for 32 months following surgical treatment.

[Clinical investigation of male infertile patients with chromosomal anomalies].

We investigated 470 male patients who came to the Reproduction Medical Center of Yokohama City University Medical Center complaining of infertility between April 2,000 and August 2013. We analyzed the chromosomes of 90 patients whose sperm concentration was below 1.0 × 107/ml. Nineteen of the 90 (21.1%) patients showed sex chromosomal anomalies including 12 Klinefelter syndrome (47, XXY or 46, XY/47, XXY), Robertsonian translocation, 2 autosome-autosome translocation, Y-autosome translocation, 46, X with marker chromosome (46, Xmar⁺), XX male and Y chromosome macrodeletion (46, XYq-). While patients with chromosomal abnormalities except XX male or some of 46, XYq- may succeed in reproduction using testicular sperm extraction-intracytoplasmic sperm injection, we need to inform the patients about the risks of chromosomal abnormalities in the resulting fetus.

[Case of azoospermia patient with a chromosomal abnormality considered a ring Y chromosome].

A 43-year-old man came to our clinic complaining of infertility and semen analysis showed azoospermia. Analysis of chromosomes showed a mosaic 45, XO/46, X, ＋mar1/46, X, ＋mar2 karyotype, and the marker chromosomes were considered to be two kinds of ring Y chromosomes. Y chromosome microdeletion analysis showed partial deletion of Azoospermic Factor (AZF) a, and complete deletion of AZFb and AZFc. The patient gave up having a child because these results indicated that no sperm would be collected even if Testicular Sperm Extraction (TESE) were performed.

[A case of male infertility caused by drug-induced hyperprolactinemia].

A 46-year-old man complaining of infertility was referred to our hospital. He was diagnosed with oligozoospermia, asthenozoospermia and hyperprolactinemia probably induced by sulpiride for depression, because semen quality gradually improved after cessation of sulpiride administration. Five months after the cessation, his serum prolactin level declined to the normal level, and his wife achieved spontaneous pregnancy.

[Renal metastasis from prostatic adenocarcinoma : a case report].

We report a case of renal metastases from prostate cancer to show that the possibility of tumor metastasis, although rare, should be considered in the differential diagnosis of renal mass. A 67-year-old man was found to have a renal mass on computed tomographic scan incidentally. He had had total androgen blockage (bicalutamide + leuprolerin) and chemotherapy (docetaxel hydrate ) for treatment of prostate cancer discovered 33 months ago. On the basis of the clinical features and radiologic results, the patient was thought to have a second malignant tumor, and we performed left nephrectomy. The pathological finding of this case was renal metastasis from prostatic adenocarcinoma. He died 18 months postnephrectomy.

[Perivesical abscess secondary to ruptured appendicitis : a case report].

A 38 year-old man was referred to our hospital for high fever and lower abdominal pain. The laboratory data showed his inflammatory state with a few puss cells in the urine analysis. Computed tomography (CT) scan and magnetic resonance imaging (MRI) scan demonstrated perivesical abscess and the cystoscopy on the day just before the operation revealed no abnormal findings in the bladder mucosa. In the operation, under the preoperative diagnosis of pyourachus, the appendix with the tip open was found inside the abscess cavity. Therefore, appendectomy and partial cystecomy were carried out. On the grounds of the pathological findings ; remarkable inflammatory change in the perivesical fatty tissue and slight inflammatory lesions in the subserous layer of the appendix, in addition to the clinical course and the retrospective findings of the preoperative MRI scan : existence of a tubular structure connecting with the abscess cavity, the final diagnosis was made as perivesical abscess secondary to ruptured appendicitis. This case is reported with a brief discussion as to the diagnosis and treatment.

[Chylorrhea after left nephroureterectomy].

A 74-year old man developed chylorrhea after transperitoneal left nephrouretectomy for renal pelvic malignancy. This patient had received ureterolithotomy for the left ureteral stones twice about 30 years ago. He was treated successfully with peripheral parenteral nutrition and subcutaneous administration of Octreotide, an available somatostatin analog with a long half-life. Postoperative chylorrhea is a rare complication that may result in serious complications such as nutritional and immunological disturbance, due to a loss of body proteins and lymphocytes. Chylorrhea, therefore, should be treated adequately and immediately at the time of diagnosis. Octreotide, which is effective in the treatment of chylorrhea and has no adverse effects, is considered a therapeutic choice.

[Two cases of granulocyte-colony stimulating factor-producing infiltrating urothelial carcinoma of the kidney].

We report two cases of granulocyte-colony stimulating factor (G-CSF) producing infiltrating urothelial carcinoma of the kidney. Case 1: A 58-year-old woman was referred to our hospital for fever and right back pain. Blood test showed severe inflammation and computed tomographic (CT) scan demonstrated swelling and irregular enhancement of the right kidney. Under the diagnosis of pyonephrosis or renal tumor, we performed right radical nephrectomy. The patient died of lung and liver metastases 6 months postoperatively despite of adjuvant chemotherapy. Case 2: A 76-year-old woman was referred to our hospital for a chief complaint of gross hematuria. Retrograde pyelogram and CT scan demonstrated a right renal pelvic tumor and we performed right nephroureterectomy. The patient died of liver and lung metastases 4 months postoperatively. The pathological and histochemical findings of these two cases were G-CSF producing infiltrating transitional cell carcinoma of the kidney. They showed marked leukocytosis and elevation of serum G-CSF levels. To our knowledge, they are the first two cases of G-CSF producing infiltrating urothelial carcinoma of the kidney in Japanese literature.

[Successful embolization of renal artery pseudoaneurysms following a stab wound].

A 21-year-old man was brought to our hospital for a single stab wound in the left flank inflicted with a suicidal intent. The initial computed tomographic (CT) scan of the patient with hypotension revealed a perirenal hematoma. Laparotomy was carried out in order to rule out any wounds of intra-abdominal organs. There was no active bleeding in any intraperitoneal organs, but a stab wound in the left renal lower pole, 2 cm in length, was recognized and considered as the cause of the hematoma. Therefore, the wound of the renal parenchyma, which was accompanied by neither urinary leakage nor fresh bleeding, was closed. The patient received a blood transfusion, because gross hematuria appeared three days postoperatively and severe anemia ensued. Then, enhanced CT scan revealed a left intrarenal pseudoaneurysm. By the following arterial angiography the renal pseudoaneurysm with arteriovenous fistula was confirmed and successfully occluded using selective arterial embolization twice. Transcatheter arterial embolization is considered safe and effective and should be chosen as a first-line therapy for controlling hemorrhage from renal arterial pseudoaneurysms.

Enhanced expression of asparagine synthetase under glucose-deprived conditions protects pancreatic cancer cells from apoptosis induced by glucose deprivation and cisplatin.

Although hypovasculature is an outstanding characteristic of pancreatic cancers, the tumor cells survive and proliferate under severe hypoxic, glucose-deprived conditions caused by low blood supply. It is well known that the hypoxia-inducible factor-1 pathway is essential for the survival of pancreatic cancer cells under hypoxic conditions. To discover how pancreatic cancer cells adapt to glucose deprivation as well as hypoxia, we sought glucose deprivation-inducible genes by means of a DNA microarray system. We identified 63 genes whose expression was enhanced under glucose-deprived conditions at >2-fold higher levels than under normal glucose conditions. Among these genes, asparagine synthetase (ASNS) was studied in detail. Although it is known to be associated with drug resistance in leukemia and oncogenesis triggered by mutated p53, its function is yet to be determined. In this study, we found that glucose deprivation induced the overexpression of ASNS through an AMP-activated protein kinase-independent and activating transcription factor-4-dependent manner and that ASNS protects pancreatic cancer cells from apoptosis induced by glucose deprivation itself. ASNS overexpression also induced resistance to apoptosis triggered by cisplatin [cis-diammine-dichloroplatinum (CDDP)] and carboplatin, but not by 5-fluorouracil, paclitaxel, etoposide, or gemcitabine. We show that glucose deprivation induces the activation of c-jun NH(2)-terminal kinase (JNK)/stress-activated protein kinase (SAPK) in a mock transfectant but not in an ASNS transfectant. Consequently, an inhibitor of JNK/SAPK decreased the sensitivity of pancreatic cancer cells to apoptosis by glucose deprivation and CDDP. These results strongly suggest that ASNS is induced by glucose deprivation and may play a pivotal role in the survival of pancreatic cancer cells under glucose-deprived conditions.

High-Acquisition-Rate Single-Shot Pump-Probe Measurements Using Time-Stretching Method.

Recent advances of ultrafast spectroscopy allow the capture of an entire ultrafast signal waveform in a single probe shot, which greatly reduces the measurement time and opens the door for the spectroscopy of unrepeatable phenomena. However, most single-shot detection schemes rely on two-dimensional detectors, which limit the repetition rate of the measurement and can hinder real-time visualization and manipulation of signal waveforms. Here, we demonstrate a new method to circumvent these difficulties and to greatly simplify the detection setup by using a long, single-mode optical fiber and a fast photodiode. Initially, a probe pulse is linearly chirped (the optical frequency varies linearly across the pulse in time), and the temporal profile of an ultrafast signal is then encoded in the probe spectrum. The probe pulse and encoded temporal dynamics are further chirped to nanosecond time scales using the dispersion in the optical fiber, thus, slowing down the ultrafast signal to time scales easily recorded with fast detectors and high-bandwidth electronics. We apply this method to three distinct ultrafast experiments: investigating the power dependence of the Kerr signal in LiNbO3, observing an irreversible transmission change of a phase change material, and capturing terahertz waveforms.

Evaluation of brilliance and visibility of fluorescence and chemiluminescence solution for training of preparing injections.

Personnel who prepare and administer chemotherapeutic agents have been reported to develop untoward effects. The use of appropriate techniques for preparing these agents is encouraged, and educational training systems that involve the use of a fluorescent or chemiluminescence reagent as placebos have been established to minimize potential exposure to these agents. However, the optimum conditions for the use and visibility of these placebos remain obscure. In this study, our results indicated that the fluorescence intensity of fluorescent reagent decreased when it was used at a concentration greater than 0.01%. Because drops created due to splashes and leaks are extremely small and easily evaporate, it is possible that the fluorescence resulting from such drops readily disappears despite using an anti-evaporation reagent. We also developed a method to evaluate the visibility of the small drop; using this method, we determined the distance at which the drop present on the pin could be seen by the observer. The distance at which the drop was clearly recognized as a pinpoint by using the fluorescence method was almost comparable to that for the chemiluminescence method. In the chemiluminescence method, the drop on the pin was faintly visible as a slightly bright area because of low background when observed at a certain distance that was much greater than that at which the drop was clearly visible; however, such an area was not observed in the fluorescence method. The results of our study will help in the selection of a training method depending on the situation.