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Bladder cancer is believed to develop through reversible premalignant stages followed by irreversible steps, and ending in invasive cancer giving rise to distant metastases. Because of the variation in the clinical course it has also been suggested that different forms of cancer develop along different molecular pathways leading to tumor presentations of various malignant potential. Today we treat and prognosticate bladder cancer on the basis of clinical and histologic findings that are insufficient to assess all the biologic potential of these tumors. Understanding the pathogenesis of bladder cancer might lead to a more precise identification of particular tumors with regard to clinical aggressiveness, resulting in individualized strategies for treatment and prophylaxis. Bladder cancer is seldom diagnosed in its preclinical stage, it is instead detected at cystoscopy and virtually never recognized as an incidental finding on autopsy. Therefore its ''natural history'' largely reflects that of ''treated'' disease. The true incidence of premalignant and malignant epithelial changes is not known. Incidences of hyperplasia and dysplasia of &#44 10% and &#44 5%, respectively and only occasional findings of cancer itself were reported in two autopsy series. Urothelial dysplasia is generally believed to be premalignant and a putative precursor of invasive cancer but unfortunately there has been a lack of standardization in terms of terminology and diagnosis. There is also a need for an agreed definition of the boundary between premalignancy, i.e. urothelial changes that have some but not all the features of carcinoma in situ, and malignancy, especially when considering potentially harmful treatments to prevent this transition. Most new diagnostic tools available and being tested today compare new detection techniques with traditional methods such as cytology or conventional histology of malignant rather than premalignant changes. There is probably also a short preclinical latency, as implied by the incidental findings of bladder cancer at autopsy, which makes it necessary to define how and when to promote early detection and treatment. Future studies therefore have to concentrate on methods for early detection of disease as well as characterization of host susceptibility, evaluation of exposure to carcinogens and potential effects of preventive measures. It is also likely that the improved tools of molecular prognostication will allow us to design trials more precisely in order to tailor therapeutic strategies. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate how the subjective impression of English speech would change when pause duration at punctuation marks was varied. Two listening experiments were performed in which written English speech segments were rated on a variety of evaluation items by both native-English speakers and non-native speakers (native-Chinese speakers and native-Japanese speakers). The ratings were then subjected to factor analysis. In the first experiment, the pauses in three segments were made into the same durations, from 0.075 to 4.8 s. Participants rated the segments on 23 evaluation items on a rating scale from 1 to 10. A varimax rotation after PCA (principal component analysis) led to two factors that were related to speech style. These two factors could be interpreted as representing speech naturalness and speech rate. Speech segments with a pause duration of 0.6 s received the highest naturalness evaluation, while perceived speech rate decreased as the physical pause duration increased, without any changes in utterance segments. In the second experiment, a full-factorial design of pause durations (0.15, 0.3, 0.6, 1.2, and 2.4 s) within and between sentences, i.e., for commas and for periods, was implemented in two speech segments. The original speech segments and speech segments without any pauses were also included as control conditions. From ratings on 12 evaluation items, similar to Experiment 1, two factors representing speech naturalness and speech rate were obtained. The results showed again that the perceived speech rate decreased with an increase only in pause duration. As for speech naturalness, the highest evaluations occurred when pause durations were 0.6 s within sentences, and either 0.6 or 1.2 s between sentences. This recommends fixing all pause durations to 0.6 s as a practical way to train non-native speakers to make their spoken English appear more natural., Competing Interests: Author YN is employed by Sound Corporation, Fukuoka, Japan. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liu, Nakajima, Chen, Arndt, Kakizoe, Elliott and Remijn.)

Objectives: The present study aimed to identify patients with locally advanced rectal cancer in whom preoperative radiotherapy (RT) can be omitted., Methods: This study was a retrospective multi-institutional study for patients with pathological stage II and III rectal cancer who underwent surgery without preoperative therapy between January 2008 and December 2012. Clinicopathological factors were examined by univariate and multivariate analyses to clarify independent risk factors of local recurrence (LR)., Results: The 5-year cumulative local recurrence rate (LRR) of 815 patients was 11.2%. Independent predictive factors of LR were determined by a multivariate analysis to be a tumor location of <10 cm from the anal verge, a tumor diameter of ≥50 mm, undifferentiated histological type, and advanced T-N substage (T3N+ or T4Nany). In lower rectal cancer located <10 cm from the anal verge (n = 510), the 5-year cumulative LRR of patients without any remaining three factors was 4.4%, with one factor was 13.0%, with two factors was 22.2%, and with all three factors was 41.6%., Conclusions: Preoperative RT may be omitted in patients with lower rectal cancer with no risk factors. However, in addition to the present risk factors, we need to further examine the extramural vascular invasion (EMVI) status and circumferential resection margin (CRM) using magnetic resonance imaging (MRI) findings. The trial was registered with UMIN Clinical Trails Registry, number 000006039., Competing Interests: Conflicts of Interest There are no conflicts of interest., (Copyright © 2021 by The Japan Society of Coloproctology.)

Purpose: The purpose of this study was to investigate the relationship between the fluorescence on indocyanine green fluorescent imaging (ICG-FI) and the histopathological findings of regional lymph node (LN) metastasis of splenic flexural colon cancer., Methods: From July 2013 to December 2018, consecutive patients with splenic flexural colon cancer with a preoperative diagnosis of N0 who underwent laparoscopic surgery were enrolled. The distribution of cancer sites in metastatic LNs (completely/not completely occupied by metastatic foci) was evaluated with hematoxylin and eosin-stained preparations. We compared the relationship between the distribution of cancer site and fluorescence of paraffin block in metastatic LNs., Results: Seventy-two patients were enrolled, of whom 13 (18.1%) had metastatic LNs. A total of 25 metastatic LNs were evaluated. The median short axis of the occupied LNs was 4.5 mm, which was significantly larger than that of the non-occupied LNs (3.0 mm; p = 0.036). In the near-infrared observation of the paraffin block, the completely occupied LNs showed no fluorescence, regardless of the LN size, but 8 of 10 non-occupied LNs showed fluorescence (p < 0.001). Even the non-occupied LNs that showed fluorescence, the cancer site did not show fluorescence., Conclusions: The occupied LNs showed no fluorescence, but 80% of the non-occupied LNs showed fluorescence. Even in non-occupied LNs that showed fluorescence, the cancer site did not show fluorescence. This demonstrated LN dissection should not be omitted, even if no fluorescence is noted on intraoperative ICG-FI.

A 63-year-old man showed massive ascites, massive pleural effusion, severe lower-extremity edema, and repeated esophageal variceal bleeding. Two-year previously, he received 13-courses of oxaliplatin-based chemotherapy (OBC) followed by associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) for multiple colorectal cancer liver metastases but developed a solitary remaining liver metastasis and multiple lung metastases 2 months after the ALPPS, for which multiple regimens of chemotherapy were conducted. The symptoms were considered attributable to the OBC-associated portal-hypertension. Water-retention symptoms were mitigated by the use of tolvaptan but the variceal bleeding necessitated frequent endoscopic treatments and disallowed restarting antineoplastic treatment. Transjugular intrahepatic portosystemic shunt (TIPS) was considered undesirable because TIPS in this patient might have prohibited future repeat hepatectomy. Thus, the patient underwent splenectomy and surgical portosystemic shunting. Since then, the portal-hypertension symptoms were completely resolved. Thereafter, chemotherapy was able to be recommenced. Moreover, repeat hepatectomy was performed. A literature review demonstrated that radiological and/or surgical interventions for the OBC-associated portal-hypertension have been reported in 31 cases to date. However, this report is the first to show a case of successful treatment of the OBC-associated portal-hypertension with splenectomy and surgical portosystemic shunting, which allowed subsequent chemotherapy followed by repeat hepatectomy.

Regorafenib is widely used for patients with metastatic colorectal cancer, following disease progression with standard therapies.However, regorafenib has severe toxicities; therefore, careful monitoring and treatment are necessary.Several studies have investigated the efficacy of initial dose reductions.We started regorafenib doses from 80 mg, with a duration of 1 week on and 1 week off, after which we gradually increased the dosage and duration.From September 2015 to March 2017, we treated 7 consecutive patients who received regorafenib following standard chemotherapy for metastatic colorectal cancer.The average age was 73 years and average BMI was 23.3.The average total dose was 15,960(2,240-28,000)mg, and the average treatment duration was 243(50-379)days.The mean survival from the start of regorafenib was 399(median 407, 262-622)days.Adverse events of Grade 3 or higher were observed in 1 patient(14%).

We investigated the correlation between computed tomography (CT) density of ureteral stones and their mineral composition. A total of 346 patients who underwent ureteroscopic lithotripsy for calculi all fragments of which were acquired at a single institution from 2009 to 2011 were analyzed. The maximum and mean CT densities were measured preoperatively. A mineral analysis revealed calcium oxalate in 203 (58.7 %), mixed calcium oxalate and calcium phosphate in 78 (23.0 %), calcium phosphate in 18 (5.2 %), uric acid in 8 (2.3 %), struvite in 3 (0.9 %), and cysteine in 5 (1.4 %). The mean Hounsfield units (HUs) of the CT density were 1046 HUs in calcium oxalate, 1101 HUs in mixed calcium oxalate and calcium phosphate, 835 HUs in calcium phosphate, 549 HUs in uric acid, 729 HUs in struvite, and 698 HUs in cystine. The HUs in calcium oxalate were significantly higher than those in uric acid (p < 0.01) and struvite (p < 0.01). Those in monohydrate stones were significantly higher, compared with dehydrate stones (p < 0.05). We analyzed the largest number of stones than each published study to correlate their mineral composition and CT density. Calcium component stones showed significantly higher CT densities than other types.

Background: Tyrosine kinase inhibitors (TKIs) have become the mainstay of treatment for advanced renal cell carcinoma (RCC), but it has been unclear whether the antitumor effect of TKIs depends on the organ where the RCC metastasis is located. We previously reported that the FDG accumulation assessed by FDG PET/CT, was a powerful index for evaluating the biological response to TKI. In this study we investigated the differences in FDG accumulation and the response to TKI as assessed by FDG PET/CT among various organs where RCC were located., Methods: A total of 48 patients with advanced RCC treated with a TKI (25 with sunitinib and 23 with sorafenib) were evaluated by FDG PET/CT before and at 1 month after a TKI treatment initiation. The maximum standardized uptake value (SUVmax) of all RCC lesions were measured and analyzed., Results: We evaluated 190 RCC lesions. The pretreatment SUVmax values (mean ± SD) were as follows: in the 49 lung metastases, 4.1 ± 3.3; in the 40 bone metastases, 5.4 ± 1.6; in the 37 lymph node metastases, 6.7 ± 2.7; in the 29 abdominal parenchymal organ metastases, 6.6 ± 2.7; in the 26 muscle or soft tissue metastases, 4.4 ± 2.6; and in the nine primary lesions, 8.9 ± 3.9. Significant differences in the SUVmax were revealed between metastases and primary lesions (p = 0.006) and between lung metastases and non-lung metastases (p < 0.001). The SUVmax change ratios at 1 month after TKI treatment started were -14.2 ± 48.4% in the lung metastases, -10.4 ± 23.3% in the bone metastases, -9.3 ± 47.4% in the lymph node metastases, -24.5 ± 41.7% in the abdominal parenchymal organ metastases, -10.6 ± 47.4% in the muscle or soft tissue metastases, and -24.2 ± 18.3% in the primary lesions. There was no significant difference among the organs (p = 0.531)., Conclusions: The decrease ratio of FDG accumulation of RCC lesions evaluated by PET/CT at 1 month after TKI treatment initiation was not influenced by the organs where the RCC metastasis was located. This result suggests that TKIs can be used to treat patients with advanced RCC regardless of the metastatic site.

A case of renal cell carcinoma presenting with paraneoplastic syndrome is reported. A 69-year-old man with uncontrolled diabetes was incidentally found to have a left thoracic tumor and a right renal tumor. He had intermittent fever of 39℃ or more and laboratory data showed diabetes and high C-reactive protein level. A radical nephrectomy was performed, but the neoplastic syndrome did not improve. After a second surgery consisting of complete resection of solitary bone metastasis the symptoms resolved immediately. At 6 months postoperatively, he had no reoccurence. Generally prognosis of patients with bone metastasis from renal cell carcinoma has been said to be poor, but surgical control of bone metastasis may be a key factor for the prognosis of patient with metastatic RCC in the era of targeted therapy.

A ureteral access sheath (UAS) can facilitate ureteroscopy (URS) and the retrieval of stone fragments while reducing the intrarenal pressure, thereby improving irrigate flow and decreasing the length of an operation. Ureteral stenting after URS is unnecessary for uncomplicated cases. This study examined the early removal of postoperative ureteral catheterization after URS for cases that used a UAS. A total of 93 patients underwent ureteroscopic lithotripsy with the early removal of ureteral catheterization. Sixty-three of these patients underwent surgery with the use of UAS and were analyzed in this study. Postoperative hydronephrosis was assessed using ultrasonography 3 days after the operation and computed tomography 2 weeks after operation in all patients. Post-operative complications including fever, prolonged hospitalization, frequent usage of painkillers and the re-insertion of ureteral stent were also investigated. Hydronephrosis was detected 3 days after the operation in 34 patients (54.0 %) and 2 weeks after the operation in four patients (6.3 %). No hydronephrosis was detected after a 2-month follow-up in these four patients. The mean operation time in the hydronephrosis group was significantly higher at 58.9 min than in the non-hydronephrosis group at 45.5 min (p < 0.05). Post-operative fever (38 °C) was seen in one case, the frequent usage of painkillers was seen in four cases, a prolonged hospital stay was seen in five cases, and ureteral stent re-insertion was observed in one case. The early removal of ureteral catheterization can be safely performed for the patients that undergo URS with UAS.

We report a 44-year-old female with lymphangiomyomatosis (LAM) of the kidney and retroperitoneum. Abdominal ultrasonography revealed a right kidney tumor, and she was referred to our department. Computed tomography (CT) revealed a para-aortic phyma in addition to the tumor. We performed retroperitoneal tumorectomy and partial resection of the right kidney via laparotomy. Pathological findings suggested LAM. LAM usually induces pulmonary lesions and its prognosis is relatively unfavorable. Female hormones are considered to be involved in the aggravation of LAM. The lesion may not have reached the lung in this postmenopausal woman because of the absence of these hormones.

The toxicity of platinum-based chemotherapies is a common problem for patients with advanced urothelial carcinoma. We performed a prospective study to assess the efficacy and safety of the combination chemotherapy of methotrexate, epirubicin and nedaplatin (MEN) as first-line treatment in patients with advanced urothelial carcinoma. Eligible patients had pathologically proven measurable unresectable or metastatic urothelial carcinoma. Between February 2003 and February 2006, 11 patients with a mean age of 70 years were treated every 3 weeks with methotrexate (30 mg/m(2) on day 1) and epirubicin (50 mg/m(2) on day 1) and nedaplatin (80 mg/m(2) on day 2). A median of 2.6 cycles were administered. None of the 11 patients achieved a complete response (CR), but 6 patients (55%) achieved a partial response (PR) with a median duration of response of 10 months, and no responses occurred in 4 patients. The median survival time was 11 months. Grade 4 hematological toxicities included neutropenia in 1 case (9%), thrombocytopenia in 2 cases (19%) and anemia in 1 case (9%). None of the 11 patients had febrile neutropenic episodes, and no toxic death was observed. Our results suggest that the combination chemotherapy of methotrexate, epirubicin and nedaplatin (MEN) was effective and acceptable treatment in patients with advanced urothelial carcinoma.

Although giant cell tumor of bone (GCT) is characterized by the extensive multinucleated giant cells among mononuclear stromal cells, proliferation of these cells and multinucleation are not without limit in certain cases. Few studies on oncogenesis of GCT have focused on the negative growth control, including growth arrest and apoptosis. The purpose of this study was to investigate the mechanism of cell death in multinucleated giant cells and stromal cells of GCT. In this study, we have demonstrated that GCT cells can undergo apoptosis. The cells in surgical specimen were positively stained in situ nick end labeling methods, and electron micrographs showed the morphological changes associated with apoptosis in some of stromal cells and multinucleated giant cells. A candidate responsible for this apoptosis was then examined using cultured GCT cells. We focused on Fas that is a major trigger of apoptosis. Cultured GCT cells expressed detectable amount of Fas on their surface. Although GCT cells did a little undergo apoptosis following treatment with anti-Fas alone, combination treatment with cyclohexamide led to an increase in apoptosis of the GCT cells. These data suggested that the sensitizing activity of cyclohexamide on anti-Fas mediated cytotoxicity could happen in vitro.