Detection bias in open-label trials of anticancer drugs: a meta-epidemiological study.

OBJECTIVES: In anticancer clinical trials, particularly open-label trials, central reviewers are recommended to evaluate progression-free survival (PFS) and objective response rate (ORR) to avoid detection bias of local investigators. However, it is not clear whether the bias has been adequately identified, or to what extent it consistently distorts the results. Therefore, the objective of this study was to evaluate the detection bias in oncological open-label trials by confirming whether local investigators overestimate the PFS and ORR compared with the findings of central reviewers. DESIGN: Meta-epidemiological study. DATA SOURCES: MEDLINE via PubMed from 1 January 2010 to 30 June 2021. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Open-label, parallel-group superiority, randomised trials of anticancer drugs that adjudicated PFS or ORR by both central reviewers and local investigators. REVIEW METHODS: We assessed the values for the same outcome (PFS and ORR) adjudicated by both central reviewers and local investigators. A random-effects model was used to estimate the ratio of HR (RHR) for PFS and the ratio of OR (ROR) for ORR between central reviewers and local investigators. An RHR lower than 1 and an ROR higher than 1 indicated an overestimation of the effect estimated by local investigators. RESULTS: We retrieved 1197 records of oncological open-label trials after full-text screening. We identified 171 records (PFS: 149 records, ORR: 136 records) in which both central reviewers and local investigators were used, and included 114 records (PFS: 92 records, ORR: 74 records) for meta-analyses. While the RHR for PFS was 0.95 (95% CI 0.91 to 0.98), the ROR of ORR was 1.00 (95% CI 0.91 to 1.09). The results remained unchanged in the prespecified sensitivity analysis. CONCLUSIONS: This meta-epidemiological study found that overestimation of local investigators has a small impact on evaluating PFS and ORR in oncological open-label trials. However, a limitation of this study is that it did not include data from all trials; hence, the results may not fully evaluate detection bias. The necessity of central reviewers in oncological open-label trials needs to be assessed by further studies that overcome this limitation. TRIAL REGISTRATION NUMBER: CTR-UMIN000044623.

Strong chu-hai, a Japanese ready-to-drink high-alcohol-content beverage, and hazardous alcohol use: A nationwide cross-sectional study.

BACKGROUND: A new ready-to-drink premixed high-alcohol-content beverage, called strong chu-hai, was launched in Japan, and more recently, in Taiwan and Australia. We aimed to examine the popularity and association of strong chu-hai with individual alcohol use, both of which remained unclear. METHODS: We conducted a cross-sectional study using data from the Japan "Society and New Tobacco" Internet Survey conducted from February 1 to 28, 2022, in Japan. We enrolled 27,993 respondents (aged 15 to 81 years; male 48.5%), including 15,083 current alcohol users. Using inverse probability weighting of data from the 2016 Comprehensive Survey of Living Conditions on Health and Welfare, we estimated the weighted proportions of strong chu-hai users among all respondents and constructed multivariable logistic regression models to estimate the weighted odds ratios (OR) and 95% confidence intervals (CI) of strong chu-hai use for hazardous and harmful alcohol use, defined as a score ≥8 of the Alcohol Use Disorder Identification Test, among current alcohol users. RESULTS: Among all respondents, 56.2% (weighted proportions: past, 35.9%; and current, 20.3%) drank strong chu-hai. Among drinkers, both past and current strong chu-hai use, compared to never use, were associated with hazardous and harmful alcohol use (past, OR 1.73, 95% CI 1.42 to 2.12; current, OR 2.19, 95% CI 1.79 to 2.69). CONCLUSIONS: Our study found that more than half of the respondents experienced strong chu-hai consumption, suggesting that it is widely used in Japan. In addition, both past and current strong chu-hai use were associated with hazardous and harmful alcohol use among current alcohol users.

Inadequate reporting of adjudicators in open-label trials of anticancer drugs between 2017 and 2021: a methodological review.

OBJECTIVES: In open-label trials, the details of the adjudicators are essential to evaluate the risk of detection bias. We aimed to describe how the adjudicators of progression-free survival (PFS) and objective response rate (ORR) have been reported in open-label trials of anticancer drugs. STUDY DESIGN AND SETTING: A literature search was conducted using MEDLINE via PubMed. We included open-label, parallel-group superiority randomized trials that investigated the PFS and ORR of anticancer drugs for solid tumors. After screening based on the titles and abstracts, 200 articles were randomly selected from 2017 to 2021. The researchers independently checked the eligibility and collected the adjudicators' information in the protocol, registry, and original article. RESULTS: One hundred fifty five studies reported the PFS and ORR. Approximately half of the studies did not report adjudicators (47.7% in PFS and 47.6% in ORR) in the published articles. The inconsistency between the protocol/registry and the published article was 31.0% for PFS and 33.5% for ORR. The prespecified outcomes were not reported in 5.2% of the studies evaluating PFS and 4.5% evaluating ORR. CONCLUSION: This methodological review found that adjudicators were poorly and inconsistently reported between the protocol/registry and the final publication in open-label trials of anticancer drugs.

Medical history of nocturnal enuresis during school age is an independent risk factor for nocturia in adults: The Nagahama study.

AIM: To evaluate the relationship between nocturia and medical history of nocturnal enuresis: two conditions where diurnal urination rhythm is disturbed. METHODS: The Nagahama study is a longitudinal population-based health survey involving people aged 30-75 years in Nagahama city, Japan. Our analysis included 5,402 participants who completed enuresis and International Prostate Symptom Score questionnaires. Associations between nocturnal enuresis and nocturia were evaluated cross-sectionally and longitudinally with three models: (1) univariate analysis; (2) adjusted for basic characteristics (e.g., age, sex, body mass index, activity, alcohol, and smoking); and (3) adjusted for basic and clinical variables (e.g., hyperglycemia, hyperlipidemia, hypertension, renal insufficiency, insomnia, obstructive sleep apnea, and mental health). RESULTS: In total, 1,613 participants (29.9%) had a medical history of enuresis. The mean night-time frequency was 0.73 at baseline and 0.85 at the 5-year follow-up. The cross-sectional analysis showed participants with a medical history of enuresis had night-time frequency more often than those without this history (0.84 vs. 0.68, p < .0001). Significant differences were observed in Models 2 (p < .0001) and 3 (p < .0001). The longitudinal analysis showed nocturia progression was significantly related to a history of enuresis, with odds ratios of 1.32 (p < .0001) in Model 1, 1.21 (p < .01) in Model 2, and 1.22 (p < .01) in Model 3. CONCLUSIONS: Medical history of enuresis during school age was significantly related to nocturia in adulthood in the cross-sectional analysis, and to progression to nocturia in the longitudinal analysis. These two conditions may possess a common causative association.

Lifestyle habits associated with nocturnal urination frequency: The Nagahama study.

BACKGROUND: Nocturia is a risk factor for poor quality of life and increased mortality. This study was aimed to clarifying dietary habits, eating behaviors, and sleep characteristics associated with nocturia to identify modifiable lifestyle factors for nocturia. METHODS: This cross-sectional study included 5683 community residents (64.5 ± 7.7 years old). The frequency of nocturnal urination was recorded for 1 week using a sleep diary. The frequency of food intake, unfavorable eating behaviors, and sleep characteristics that may have influence on salt intake and wasting were obtained using a structured questionnaire. RESULTS: The frequency of nocturnal urination was increased with age (ß = .312, P < .001). Other basic factors associated with the frequency were the male sex (ß = .090), hypertension (ß = .038), sleep apnea (ß = .030), B-type natriuretic peptide level (ß = .089), and spot urine sodium excretion (ß = -.058). Dietary factors independently associated with nocturnal urination frequency were coffee (≥1 time/day: ß = -.059, P < .001) and green vegetable consumption (≥1 time/week: ß = -.042, P = .001), whereas habitual intake of dairy products, miso soup, and alcohol were not associated with urination frequency. Later bedtime was inversely associated with nocturnal urination frequency independent of sleep duration (before 23:00: ß = -.096; before 24:00: ß = -.225; after midnight: ß = -.240; all P < .001). CONCLUSION: Coffee and green vegetable consumption and later bedtime but not sleep duration are lifestyle factors associated with nocturnal urination frequency.

Bladder urothelial carcinoma producing insulin-like growth factor II: A case report.

INTRODUCTION: Non-islet cell tumor hypoglycemia is a rare paraneoplastic syndrome associated with tumors. Although it mainly occurs in solid tumors of mesenchymal and epithelial origin, but rarely also in hematopoietic and neuroendocrine origin. CASE PRESENTATION: We describe a 65-year-old man with a muscle-invasive bladder urothelial carcinoma, which rapidly progressed against systemic chemotherapy consisting of gemcitabine and cisplatin. Notably, the patient developed hypoglycemia at the terminal stage of the disease. Pathological diagnosis was giant cell urothelial carcinoma, which was strongly positive for insulin-like growth factor-II in immunohistochemistry. We established patient-derived xenograft from insulin-like growth factor-II producing bladder urothelial carcinoma that caused non-islet cell tumor hypoglycemia. Although we evaluated the efficacy of the neutralizing antibody, there was no statistically significant inhibitory effect on tumor growth. CONCLUSION: To the best of our knowledge, this is the first report of insulin-like growth factor-II-producing urothelial carcinoma that have been recapitulated in a patient-derived xenograft model.

Standardized and Simplified Retroperitoneal Lymph Node Dissection During Retroperitoneal Laparoscopic Radical Nephroureterectomy for Urothelial Carcinoma of the Upper Ureter or Renal Pelvis: En Bloc Resection Technique.

OBJECTIVE: To describe our en bloc technique of retroperitoneal lymph node dissection (RPLND) during retroperitoneal laparoscopic radical nephroureterectomy for upper urinary tract urothelial carcinoma and evaluate perioperative outcomes. METHODS: From 2002 to 2015, 114 patients with urinary tract urothelial carcinoma located at the pelvis or upper or middle ureter underwent retroperitoneal laparoscopic radical nephroureterectomy at 2 institutions. Performance of RPLND began in February 2009. The template of RPLND included the renal hilar and para-aortic lymph nodes (left side) and the renal hilar, paracaval, retrocaval, and intra-aortocaval lymph nodes (right side). After incising Gerota fascia longitudinally, the aorta (left side) or inferior vena cava (right side) was exposed, and the lymphatic and surrounding fatty tissue in the template and kidney was dissected in a single monoblock. Preoperative data were compared between the RPLND and the no-RPLND groups using propensity score matching. RESULTS: In total, 32 matched pairs were evaluated. RPLND was successfully accomplished without open conversion in all cases. The operative time in the RPLND group was approximately 100 minutes longer than that in the no-RPLND group, but there was no significant difference in the blood loss volume or complication rate. The pathologic stages were similar in both groups. The mean number of retrieved lymph nodes was 10.7 (range 3-27), and lymph node metastasis was detected in 5 (16%) cases. CONCLUSION: Retroperitoneoscopic en bloc RPLND permits complete and radical removal of the lymphatic tissue contained in the RPLND template. Our en bloc technique is a safe and feasible procedure with comparable blood loss and complication rates.

[Prostate Cancer Diagnosed during Androgen Replacement Therapy for Late-Onset Hypogonadism Treatment: A Case Report].

We report a 60-year-old man with prostate cancer diagnosed during androgen replacement therapy (ART) for late onset hypogonadism after surgery for pituitary adenoma. He was refered to the department of urology since prostate specific antigen values were elevated after 6 months of ART. After the diagnosis of prostate cancer, ART was discontinued, and robot-asssited laparoscopic radical prostatectomy with pelvic lymphadenoctomy was performed. Pathological examination revealed Gleason score 4 + 5 prostate adenocarcinoma with seminal vesicle invasion and lymph node metastasis(pT3bN1). He has stayed biochemically and radiologically disease-free 33 months postoperatively.

[The Efficacy of a Released Ultrasonic Lithotripsy in Percutaneous Nephrolithotomy : Randomized Trial Comparing Swiss LithoClast® Master Versus Swiss LithoClast®].

We prospectively randomized total 29 patients with renal stones into two groups between Aug 2014 and March 2016. The US group was treated using a ultrasonic lithotripter (Swiss LithoClast® Master) and the PN group was treated with a pneumatic lithotripter (Swiss LithoClast® ). We compared treatment outcomes in these groups. The US group consisted of 17 patients and the PN group 12 patients. There was no significant difference between the groups in baseline characteristics (age, sex, body mass index, side, stone size, and density). There was no significant difference in total operative time (p＝0.63), stone-free rate (p＝ 0.19), hemoglobin deficit (p＝0.49), or rate of postoperative sepsis (p＝0.99) between the two groups. However, intracorporal stone disintegration and removal time was significantly shorter in the US group than the PN group (p＝0.029). These results suggest that the ultrasonic lithotripter can be superior to the existing pneumatic lithotripter in saving intracorporal stone disintegration and removal time in percutaneous nephrolithotomy.

[THE OPTIMAL TROCAR PLACEMENT FOR LAPAROSCOPIC EXCISION OF URACHAL REMNANTS].

(Objective) Although laparoscopic excision of urachal remnants has been applied widely, the standard surgical method has yet to be established. The aim of this study, therefore, was to evaluate perioperative outcome and surgical techniques, including the trocar placement at our institution. (Subjects and methods) A total of 20 patients with urachal remnant were treated using laparoscopic surgery between October 2002 and August 2016. 3 trocars were inserted in the peritoneal cavity. Camera trocar was placed at right side of umbilicus and two working trocars were placed at the upper side of umbilicus and right lower quandrant. A 5 mm, 30° angled lens camera was used during operation. (Results) The mean age was 27 years old. There were 16 males and 4 females. The classifications of urachal remnants were urachal sinus (n=18) and urachal diverticulum (n=2). Umbilical excision was performed in 18 case and partial cystectomy were required in 4 cases. 4 trocars were inserted in only one case due to severe adhesion in the peritoneal cavity. Laparoscopic excision was successfully completed in all cases. The mean operative time was 220 minutes and the mean blood loss was minimal. The complications occurred in 5 cases including small intestinal injury (n=2), peritonitis (n=1), wound infection (n=1), intestinal obstruction (n=1) and acute renal failure (n=1) (intestinal obstruction and acute renal failure were occurred in the same case). (Conclusion) Although there are problems such as shortening the operative time and reducing complications, our unique port placement enables good surgical view and easy suturing during partial cystectomy.

[CHYLOUS LEAKAGE AFTER LAPAROSCOPIC RENAL AND ADRENAL SURGERY].

(Objectives) It is recognized that Chylous leakage is a rare complication but is a relevant clinical problem after major abdominal surgery. It was occasionally reported in urologic surgery, but the data about its incidence and treatment outcome is still lacking. In this study, we reviewed our cases of chylous leakage after laparoscopic adrenalectomy or nephrectomy. (Patients and methods) From January 2005 to September 2014, laparoscopic adrenalectomies or nephrectomies were performed in 300 patients. The factors that affected the development of chylous leakage were analyzed. (Results) The overall incidence of chylous leakage was 4.3% (13 of 300 cases). All chylous leakage was seen on the left side, and it was commonly developed in patients with lymph node dissection or excessive hilar dissection around the left renal pedicle. Importantly, all cases were successfully managed conservatively by a low fat diet with or without octreotide. (Conclusions) Our results suggest that chylous leakage is not a rare complication after laparoscopic adrenalectomy or nephrectomy, but most cases can be treated conservatively. Chylous leakage can occur in patients with lymphadenectomy or hilar dissection on the left side.

Laparoscopic Partial Cystectomy With Excision of Mesh Migration Into the Bladder Following Repair of Inguinal Hernia.

Migration of hernia mesh into the bladder is a rare complication of inguinal hernioplasty. We present the case of an 85-year-old man who complained of hematuria and fever some 20 years after right hernioplasty. Cystoscopy and computed tomography revealed mesh migration into the right anterior wall of the bladder. Laparoscopic partial cystectomy with excision of the migrated mesh was performed successfully. To our knowledge, this is the first case of mesh migration into the bladder treated by laparoscopic partial cystectomy.