Gut feeling for the diagnosis of cancer in general practice: a diagnostic accuracy review.

OBJECTIVES: Diagnostic delay in cancer is a challenge in primary care. Although screening tests are effective in diagnosing some cancers such as breast, colorectal and cervical cancers, symptom-based cancer diagnosis is often difficult due to its low incidence in primary care and the influence of patient anxiety, doctor-patient relationship and psychosocial context. A general practitioner's gut feeling for cancer may play a role in the early diagnosis of cancer in primary care where diagnostic resources are limited. The aim of this study is to summarise existing evidence about the test accuracy of gut feeling (index test) in symptomatic adult patients presenting to general practice, compared with multidisciplinary team-confirmed diagnosis of cancer (reference standard). DESIGN: Diagnostic accuracy review following Cochrane methods was performed. DATA SOURCES: MEDLINE, EMBASE, Cochrane Library, the Database of Abstracts of Reviews of Effects and Medion databases. ELIGIBILITY CRITERIA: Cross-sectional, cohort and randomised studies of test accuracy that compared gut feeling (index test) with an appropriate cancer diagnosis (reference standard). No language or publication status restrictions were applied. We included all studies published before 25 March 2022. DATA EXTRACTION AND SYNTHESIS: Methodological quality was appraised, using Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) criteria. Meta-analysis with hierarchical summary receiver operating characteristic (HSROC) models was used. RESULTS: Of 1286 potentially relevant studies identified, six met the inclusion criteria. For two of the six studies, data could not be extracted despite contacting authors. No studies satisfied all QUADAS-2 criteria. After meta-analysis of data from the remaining studies, the summary point of HSROC had a sensitivity of 0.40 (95% CI: 0.28, 0.53) and a specificity of 0.85 (95% CI: 0.75, 0.92). CONCLUSIONS: Gut feeling for cancer when used in symptomatic adult patients in general practice has a relatively low sensitivity and high specificity. When the prevalence of cancer in the symptomatic population presenting in general practice exceeds 1.15%, the performance of gut feeling reaches the National Institute for Health and Care Excellence 3% positive predictive value threshold for action, which recommends urgent access to specialist care and further investigations. The findings support the continued and expanded use of gut feeling items in referral pathways.

Essential components of a definition for early antibiotic treatment failure: A scoping review.

BACKGROUND: Despite the broad global use of antibiotics, there is no established definition of early antibiotic treatment failure (EATF) to aid clinical evaluation of treatment, which leads to inconsistent assessments of drug effectiveness. AIM: This scoping review aims to identify common components of EATF definitions by synthesizing studies mentioning EATF and its relevant thesaurus matches. DESIGN: Scoping review. METHODS: This scoping review was conducted following the PRISMA Scoping review guidelines. A systematic literature search was conducted using MEDLINE (PubMed), CENTRAL, CINAHL, and Web of Science, as well as a manual Google search. Search terms were EATF and its thesaurus matches. After removing duplications, candidate studies were screened by title and abstract prior to full text searches, and quality analysis was performed on eligible studies using the Critical Appraisal Skills Programme. From each eligible study, the timing of evaluation, basic components, and detailed information for each definition of EATF were collected. The components of each definition for EATF were then summarized and counted, and finally the most common essential components were identified. RESULTS: Our systematic literature search found 2,472 candidate studies. After title and abstract screening, full text search and quality assessment, 61 studies, including 56 original studies and five reviews, were eligible for our analysis. Of these 56 original studies, 43 mentioned the timing of EATF evaluation 72 hours after the start of treatment with antibiotics. From these 43 studies, the most common indicators of EATF were extracted, among which a set of essential components for a definition of EATF were identified: mortality, vital signs, fever, symptoms, and additional treatment. CONCLUSIONS: Our scoping review uncovered five essential factors for EATF. Further study is needed to evaluate the validity of our findings.

Comparative analyses define differences between BHD-associated renal tumour and sporadic chromophobe renal cell carcinoma.

BACKGROUND: Birt-Hogg-Dubé (BHD) syndrome, caused by germline alteration of folliculin (FLCN) gene, develops hybrid oncocytic/chromophobe tumour (HOCT) and chromophobe renal cell carcinoma (ChRCC), whereas sporadic ChRCC does not harbor FLCN alteration. To date, molecular characteristics of these similar histological types of tumours have been incompletely elucidated. METHODS: To elucidate renal tumourigenesis of BHD-associated renal tumours and sporadic renal tumours, we conducted whole genome sequencing (WGS) and RNA-sequencing (RNA-seq) of sixteen BHD-associated renal tumours from nine unrelated BHD patients, twenty-one sporadic ChRCCs and seven sporadic oncocytomas. We then compared somatic mutation profiles with FLCN variants and RNA expression profiles between BHD-associated renal tumours and sporadic renal tumours. FINDINGS: RNA-seq analysis revealed that BHD-associated renal tumours and sporadic renal tumours have totally different expression profiles. Sporadic ChRCCs were clustered into two distinct clusters characterized by L1CAM and FOXI1 expressions, molecular markers for renal tubule subclasses. Increased mitochondrial DNA (mtDNA) copy number with fewer variants was observed in BHD-associated renal tumours compared to sporadic ChRCCs. Cell-of-origin analysis using WGS data demonstrated that BHD-associated renal tumours and sporadic ChRCCs may arise from different cells of origin and second hit FLCN alterations may occur in early third decade of life in BHD patients. INTERPRETATION: These data further our understanding of renal tumourigenesis of these two different types of renal tumours with similar histology. FUNDING: This study was supported by JSPS KAKENHI Grants, RIKEN internal grant, and the Intramural Research Program of the National Institutes of Health (NIH), National Cancer Institute (NCI), Center for Cancer Research.

Single-cell transcriptomes underscore genetically distinct tumor characteristics and microenvironment for hereditary kidney cancers.

Our understanding of how each hereditary kidney cancer adapts to its tissue microenvironment is incomplete. Here, we present single-cell transcriptomes of 108,342 cells from patient specimens including from six hereditary kidney cancers. The transcriptomes displayed distinct characteristics of the cell of origin and unique tissue microenvironment for each hereditary kidney cancer. Of note, hereditary leiomyomatosis and renal cell carcinoma (HLRCC)-associated kidney cancer retained some characteristics of proximal tubules, which were completely lost in lymph node metastases and present as an avascular tumor with suppressed T cells and TREM2-high macrophages, leading to immune tolerance. Birt-Hogg-Dubé (BHD)-associated kidney cancer exhibited transcriptomic intratumor heterogeneity (tITH) with increased characteristics of intercalated cells of the collecting duct and upregulation of FOXI1-driven genes, a critical transcription factor for collecting duct differentiation. These findings facilitate our understanding of how hereditary kidney cancers adapt to their tissue microenvironment.

Summary of the Clinical Practice Guidelines for Penile Cancer 2021 by the Japanese Urological Association.

Penile cancer is a rare cancer for which no medical guidelines have been established before in Japan. These guidelines aim to standardize, as much as possible, the therapeutic modality for penile cancer, for which empirical evidence is limited on a global scale, thereby bolstering therapeutic outcomes for patients with penile cancer. The new guidelines conform to the Minds Guide for Developing Clinical Practice Guidelines (2017) as much as possible. However, virtually no randomized comparative studies and meta-analyses based on such randomized studies have been conducted. Therefore, only the findings available at present were listed after conducting an exhaustive literature review of items with extremely low evidence levels and for which bodies of evidence and grades of recommendation were not evaluated. Clinical questions were set for items with a relatively large number of studies, including retrospective studies. However, since it is virtually impracticable to summarize bodies of evidence by systematic reviews, recommendation grades and evidence levels were discussed and determined by the consensus panel of the Preparatory Committee. The following were outlined: epidemiological, pathological, diagnostic, therapeutic, follow-up, and quality of life-related findings. Additionally, seven clinical questions were established to determine recommendation grades and evidence levels. We hope that these guidelines will prove to be useful to medical professionals engaged in clinical practice related to penile cancer in Japan and anticipate that critical reviews of the guidelines will lead to further refinement of the next edition.

Objective assessment of laparoscopic targeting skills using a Short-Time Power of Difference (STPOD) method.

PURPOSE: To ensure that the use of surgical training tools results in improvement of surgical skills, it is necessary to be able to measure and assess surgeons' skills. We established the Short-Time Power of Difference (STPOD) method as an evaluation tool for evaluating targeting technique. The STPOD method evaluates the distance from the actual movement of the forceps to the shortest linear path between two points in a short time period. We examined the effectiveness of the STPOD method as a new forceps kinematic analysis. METHODS: Six residents were categorized as novices and six urologists as experts. All participants performed box trainer training and LapPASS® Simulator training. During the procedure, objective scores (time, distance, and STPOD) were recorded. STPOD (Power) evaluated motion smoothness and STPOD (Stop) evaluated the stop time of the forceps. RESULTS: STPOD (Stop) on the right side of the experts was significantly lower than that of the novices in the box trainer. Furthermore, there were significant differences in the distances of left side and STPOD (Power) between the experts and the novices in the simulator. In the correlation of parameters between the box trainer and the simulator, time showed the strongest correlation, STPOD (Power) and distance showed a mild correlation. CONCLUSION: We showed the construct validity of STPOD (Power) and STPOD (Stop) using both the box trainer and the simulator. This method is a good evaluation tool for assessing a physician's skill; however, there are much more complex motions that are performed in actual surgery. Future studies are needed to focus on evaluation in an environment closer to actual surgery and comparing with other existing methods.

Case of inverted papillary urothelial carcinoma in the ureter.

INTRODUCTION: Urothelial neoplasms with a varus growth pattern are rare, and few urologists have encountered inverted urothelial carcinoma of the ureter. CASE PRESENTATION: An 82-year-old man was referred to our hospital for investigation of gross hematuria. Magnetic resonance imaging revealed nodules measuring 1-2 mm in diameter in the left upper ureter with slight reduction in signal intensity on diffusion-weighted imaging. Ureteroscopy showed a pedunculated smooth tumor that had the appearance of an inverted papilloma rather than the papillary shape typical of urothelial carcinoma. The tumor was biopsied and histopathological examination revealed a noninvasive, low-grade urothelial carcinoma with inverted multiple layers. Laparoscopic radical nephroureterectomy was subsequently performed, and a pedunculated tumor measuring 20 mm in diameter was found in the left upper ureter. The histopathological diagnosis was inverted papillary urothelial carcinoma, low-grade, pTa, pN0. CONCLUSION: This report provides the first clinical description of inverted papillary urothelial carcinoma of the ureter.

Training on a virtual reality laparoscopic simulator improves performance of live laparoscopic surgery.

INTRODUCTION: To determine whether training laparoscopic nephrectomy (LN) with a virtual reality (VR) simulator improves the performance of porcine LN. METHODS: Twelve urological residents were assigned to two groups: a training and a non-training group. All participants performed baseline assessments of LN skills and time on the LapPASS® simulator. The training group received preoperative LapPASS® training. Both groups then performed LN using a porcine model. The operations were videotaped and evaluated using the Global Operative Assessment of Laparoscopic Skills (GOALS) system. After porcine LN, the training group performed a final LN with the LapPASS® simulator. RESULTS: There was no significant difference in the operation time required for porcine LN. There were no significant differences in the total A (autonomy), B (bimanual dexterity), D (depth perception), or T (tissue handling) GOALS scores. However, the total E (efficiency) score in the training group was higher than that in the non-training group (P = .030). The final LN score with LapPASS® was significantly higher than the baseline (P = .004). CONCLUSIONS: The results of this study demonstrated that VR LN training improved performance in an actual operation. VR-based procedural simulation could become a vital part of the laparoscopic training program for residents.

[A Case of Lymphoepithelioma-Like Carcinoma of the Ureter].

Lymphoepithelioma-like carcinoma (LELC) of the ureter is very rare and only 14 previous cases have been reported. Here, we report a case of LELC of the ureter. A 76-year-old woman was admitted to our hospital complaining of gross hematuria. Left ureteral cancer was suspected by the imaging examination, and laparoscopic left total nephroureterectomy was performed. Histopathological examination showed pure type of LELC in the ureter. She is alive without disease recurrence at fifteen months after surgery.

A higher De Ritis ratio (AST/ALT) is a risk factor for progression in high-risk non-muscle invasive bladder cancer.

BACKGROUND: High-risk non-muscle invasive bladder cancer (NMIBC) is thought to be associated with a higher risk of recurrence and progression. A recent study revealed that a high De Ritis ratio was a risk factor in some solid malignancies. This study examined the importance of the De Ritis ratio as a prognostic marker in high-risk NMIBC. MATERIALS AND METHODS: A total of 138 patients who were initially diagnosed with high-risk NMIBC between January 2012 to December 2016 were enrolled in this study. The criteria for the high-risk classification followed the EAU guidelines. The recurrence-free and progression-free survival of the higher and lower De Ritis ratio groups were compared. The cut-off value of the De Ritis ratio was set at 1.35, based on a receiver operator curve analysis. RESULTS: The median observation period was 50.3 months. Among these patients, 32 (23.1%) patients developed recurrent disease and 15 (10.9%) patients showed progression. A multivariate analysis revealed that non-BCG treatment was an independent risk factor for recurrence, and a higher De Ritis ratio was an independent risk factor for cancer progression. CONCLUSIONS: The De Ritis ratio might be a risk factor for progression in high-risk NMIBC.

Correlation of urinary loss rate after catheter removal and long-term urinary continence after robot-assisted laparoscopic radical prostatectomy.

OBJECTIVES: To assess the correlation of urine loss rate after catheter removal with long-term continence after robot-assisted radical prostatectomy. METHODS: We enrolled 163 patients on whom robot-assisted radical prostatectomy was carried out and whose urine loss rate we were able to evaluate after catheter removal. Urinary incontinence was evaluated from immediately after removal of the catheter to the date of discharge, and at 1, 3, 6 and 12 months after surgery. Urine loss rate was defined as the urine loss volume divided by the total urine volume. RESULTS: The continence rates of patients with ≤1% urine loss rate on the day of catheter removal were 100% at 6 and 12 months after surgery. A multivariate analysis proved that ≤10% urine loss rate on the day of catheter removal was a significant predictor of continence at 3 months after surgery. Furthermore, the continence rate at 12 months of patients who did not achieve ≤10% urine loss rate on the day of catheter removal was 79.5%. Among them, the continence rate at 12 months of patients who achieved ≥15% urine loss rate improvement from the day of catheter removal to the next day was 95.2%; the factor differed significantly between the continence and incontinence groups at 12 months after surgery. CONCLUSIONS: The urine loss rate on the day of catheter removal is significantly related to the acquisition of urinary continence. Furthermore, our findings suggest that long-term urinary continence can be expected, even in the event of poor urine loss rate on the day of catheter removal, if it improves on the next day.

Complete response of hereditary leiomyomatosis and renal cell cancer (HLRCC)-associated renal cell carcinoma to nivolumab and ipilimumab combination immunotherapy by: a case report.

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a rare autosomal dominant disorder that results from a germline mutation in the fumarate hydratase gene (FH). Individuals with FH mutations are at risk of developing renal cell carcinoma (RCC). Patients with HLRCC-associated RCC (HLRCC-RCC) have aggressive clinical courses, but there is as yet no standardized therapy for advanced HLRCC-RCC. We report an aggressive RCC case in a 49-year-old man. Nine weeks after undergoing a total nephroureterectomy of the right kidney, he had a metastasectomy at port site. Within 14 weeks of the initial surgery, multiple recurrent tumors developed in the right retroperitoneal space. The pathological diagnosis was FH-deficient RCC. Genetic testing identified a heterozygous germline mutation of FH (c.641_642delTA), which confirmed the diagnosis of HLRCC-RCC. He received combination therapy with the immune checkpoint inhibitors (ICIs) nivolumab and ipilimumab as the first-line therapy. After 31 weeks of ICI treatment, a complete response was achieved. The disease-free condition has been prolonged for 24 months since the initial surgical treatment. This is the first case report of successful treatment of HLRCC-RCC with nivolumab plus ipilimumab. This combination immunotherapy is expected to be an effective approach to treat patients with advanced-stage HLRCC-RCC.

Gap between UAS and ureteroscope predicts renal stone-free rate after flexible ureteroscopy with the fragmentation technique.

PURPOSE: To assess the effect of our new classification on surgical outcomes after flexible ureteroscopy (fURS) for kidney stones. METHODS: We retrospectively examined 128 patients after single renal fURS procedures performed using ureteral access sheaths (UASs) with the fragmentation technique. Based on the gap (calculated by subtracting the ureteroscope diameter from the UAS diameter), enrolled patients were divided into three groups: small (< 0.6 mm), medium (0.6 to < 1.2 mm), and large space groups (≥ 1.2 mm). Stone-free (SF) status was defined as either complete absence of stones (SF) or the presence of stones < 4 mm in diameter on non-contrast computed tomography (NCCT). RESULTS: The SF rate was significantly lower in the small space group (50% in small, 97.9% in medium, 89.2% in large; p = 0.001). Perioperative complications over Clavien-Dindo Grade I were observed in 16.7%, 4.2%, and 8.1% of patients, respectively (p = 0.452). The ratio of stone volume and operative time (efficiency of stone removal) was significantly higher in the large space group compared to the small and medium space groups (0.009 ± 0.003 ml/min, 0.013 ± 0.005 ml/min, 0.027 ± 0.012 ml/min, respectively; p < 0.001). CONCLUSION: Our findings that gaps > 0.6 mm (1.8 Fr), including the combination of a 9.5-Fr UAS and a small caliber ureteroscope, improve SF rates, and larger gaps facilitate stone removal efficiency providing the basis for future development of clinical protocols aimed at improving outcomes.

A lower psoas muscle index predicts a poorer prognosis in metastatic hormone-naïve prostate cancer.

Introduction: A recent investigation revealed that sarcopenia was associated with a poorer prognosis in some solid malignancies, including prostate cancer. In most reports, sarcopenia was defined as a low psoas volume on CT. This study investigated the association of sarcopenia, determined according to the psoas muscle volume and density on CT, with the prognosis in patients with metastatic hormone-naïve prostate cancer (mHNPC). Methods: A total of 66 patients initially diagnosed with mHNPC were enrolled in this study. Skeletal muscle was evaluated according to the psoas muscle index density (PMID) on computed tomography scans. The psoas muscle volume was calculated at the level of L3 and CT density was evaluated as the mean CT density at the psoas muscle area. We divided the patients into higher and lower PMID groups. Results: The lower PMID group (on both sides) showed a poorer overall survival than the higher PMID group (Right: 32.5 vs 99.0 months in Rt PMID, P = .014; Left: 36.0 vs 100.0 months in Lt PMID, P = .029). The lower PMID group (on both sides) showed a shorter time to CRPC (Right: 9.0 vs 42.0 months in Rt PMID, P = .006; Left: 9.0 vs 31.0 months in Lt PMID, P = .005). A multivariate analysis showed that lower Rt PMID and Lt PMID were independent risk factors for poorer OS (HR:2.02, 95%CI: 1.04-3.90, P = .037, HR:2.29, 95%CI: 1.18-4.47, P = .015, respectively). For CRPC, both Rt and Lt lower PMID also showed independent risk factors for shorter time to CRPC (HR:2.39, 95%CI: 1.23-4.62, P = .010, HR:2.43, 95%CI: 1.23-4.78, P = .010, respectively). Conclusions: Among mHNPC patients, both lower PMID groups showed a poorer overall survival and shorter time to CRPC than the higher PMID groups.

Prognostic value of automated bone scan index for predicting overall survival among bone metastatic castration resistant prostate cancer patients treated with radium-223.

Introduction: The objective of this study was to evaluate automated bone scan index (aBSI) as a prognostic biomarker for overall survival (OS) in bone-metastatic, castration-resistant prostate cancer (mCRPC) patients treated with radium-223 (Ra-223). Materials and methods: We identified 42 men treated with Ra-223 for mCRPC. We investigated aBSI as an independent prognostic factor by multivariate analysis. Moreover, we evaluated the prognostic value of the aBSI after 12 weeks after the first cycle of Ra-223 administration and aBSI change from baseline to after 12 weeks (ΔBSI). Results: Median baseline PSA and aBSI were 42.8 ng/mL and 1.5%, respectively. Median OS was 20.7 months. Multivariate analysis showed that baseline aBSI was a significant prognostic factor for OS. The aBSI at 12 weeks after first Ra-223 administration also exhibited significant prognostic value for OS, while we found no evidence of prognostic value for ΔBSI. Conclusions: Baseline aBSI may be a significant prognostic factor for OS in bone-metastatic CRPC patients treated with Ra-223.

Use of metallic and polymeric ureteral stents in malignant ureteral obstruction.

Background: Malignant ureteral obstruction (MUO) is often caused by advanced intra-abdominal cancers. Effective management must be attempted, but the treatment policy is unclear. Metallic ureteral stents are one of the latest options in managing MUO. Metallic ureteral stents are superior to traditional polyurethane stents. The present study retrospectively reviewed our four institutions' experiences with treating MUO using metallic ureteral stent. Methods: A total of 45 patients who required metallic ureteral stent placement for MUO at Yokohama City University Medical Center (Yokohama, JAPAN) between January 2014 and May 2016 were analyzed. We defined stent failure as having to change the ureteral stent before the scheduled ureteral stent exchange time or having to perform percutaneous nephrostomy (PCN). Complications were defined as an unscheduled hospital visit or hospitalization caused by incompatibility, infection, and pain of the metallic ureteral stent, etc., unrelated to the primary disease. We compared stent failure and the overall survival (OS) between metallic and polymeric ureteral stents. To evaluate the workload of the medical staff, we used the NASA Task Load Index (NASA-TLX) in a total of 11 urologists. Results: During the observation period, 8 (17.8%) patients in the metallic ureteral stent group and 10 (27.8%) in the control group developed stent failure. Complications were noted in 14 (31.1%) patients in the metallic ureteral stent group and 15 (41.7%) patients in the control group. A Kaplan-Meier analysis and log-rank test showed no significant differences between two groups in the overall survival (P = 0.673). One or more complications developed in 19 (32.2%) patients in the metallic ureteral stent group and 18 (38.3%) patients in the control group (P = 0.409). Renal dysfunction after the replacement of the ureteral stent developed in 9 (15.3%) patients in the metallic ureteral stent group and 14 (29.8%) patients in the control group. No patients developed a urinary tract infection (UTI) that required hospitalization in the metallic ureteral stent group, whereas 3 (6.4%) patients in the control group had a UTI that was treated with hospitalization. The average workload score in the six subscales was analyzed, and the scores for mental demand and performance were higher in the metallic ureteral stent group, although there was no significant difference between the metallic and polymeric ureteral stent groups. Conclusions: Metallic ureteral stents showed favorable ureteral stent patency and reduced the workload for urologists.

How to reduce the risk of organ injuries during surgical instrument insertion in laparoscopic surgery: Pushing/pressing force analysis using forceps with sensors.

INTRODUCTION: In laparoscopic surgery, surgical instruments are inserted from a trocar to the target organ in a blind fashion, which carries a risk of organ injury. To clarify the risks associated with surgical instrument insertion, we measured grip strength and pushing/pressing force during surgical instrument insertion in laparoscopic surgery. METHODS: Using forceps with sensors inside a trocar, 10 urologists performed a laparoscopic procedure in pigs, in which they were asked to touch the abdominal wall. The surgeons closed their eyes during the procedure and stopped moving the forceps when they felt them come into contact with the abdominal wall. They were ordered to grip the forceps strongly or softly and to move them rapidly or slowly during the procedure. Grip strength and the pushing/pressing force when the forceps hit the abdominal wall were measured and analyzed. RESULTS: The mean pushing/pressing force when the surgeons gripped the forceps strongly and moved them rapidly (strong/rapid), strongly/slowly, softly/rapidly, and softly/slowly were 2.8, 2.0, 1.7, and 1.1 N, respectively. The pushing/pressing force was significantly greater when the surgeons gripped the forceps strongly, regardless of the forceps speed (P < .001). The pushing/pressing force was significantly greater when the surgeons moved the forceps rapidly, regardless of grip strength (P < .001). CONCLUSIONS: When surgeons insert laparoscopic instruments through trocars, the instruments should be gripped softly and moved slowly to avoid organ injuries.