Shifting risk-stratified early prostate cancer detection to a primary healthcare setting

Objective

To evaluate the feasibility of multivariable risk stratification for early prostate cancer (PCa) detection in a primary healthcare diagnostic facility with regard to its effects on the referral rate and subsequent PCa diagnoses compared to a PSA threshold of 3.0 ng/mL as the current referral indicator.

Patients and Methods

In 2014, the Erasmus MC Cancer Institute and the primary healthcare diagnostic facility STAR-SHL (located in Rotterdam city centre) initiated this observational study, in which general practitioners (GPs) could refer men who wished to undergo PCa screening to STAR-SHL for consultation by specially trained personnel. Referral recommendations to secondary healthcare were based on the outcome of application of the Rotterdam Prostate Cancer Risk Calculator (RPCRC) and were compared to the current Dutch GPs' PSA referral threshold of 3.0 ng/mL. For data collection on PCa diagnoses, the study cohort was linked to the Dutch nationwide pathology databank (PALGA).

Results

Between January 2014 and February 2021, 507 men were referred for consultation and in 495 men prostate-specific antigen (PSA) was tested. The median (interquartile range) follow-up from consultation to PALGA linkage was 43 (25–65) months. In total, 279 men (56%) had a PSA level ≥3.0 ng/mL, of whom 68% (95% confidence interval [95% CI] 63–74) were considered at low risk according to the RPCRC. Within 1 year after consultation, one of these men (0.52%; 95% CI 0.092–2.9) was diagnosed with clinically significant (cs)PCa (i.e., International Society of Urological Pathology Grade Group ≥2). Thereafter, another four (2.1%; 95% CI 0.82–5.3) low-risk men were diagnosed with csPCa. Of the high-risk men who were biopsied within 1 year after consultation (n = 61), 77% (95% CI 65–86) were diagnosed with PCa and 49% (95% CI 37–61) with csPCa.

Conclusion

In a primary healthcare diagnostic facility, the RPCRC could reduce up to 68% of referrals to secondary healthcare, as compared to a PSA referral threshold of 3.0 ng/mL. Deploying the RPCRC in this setting resulted in a high csPCa detection rate in those men biopsied. This strategy can be considered safe since the observational data showed low proportions of csPCa among men at low risk.     

Effect of b value and pre-admission of contrast on diagnostic accuracy of 1.5-T breast DWI: a systematic review and meta-analysis

Objectives

To evaluate the effect of the choice of b values and prior use of contrast medium on apparent diffusion coefficients (ADCs) of breast lesions derived from diffusion-weighted imaging (DWI), and on the discrimination between benign and malignant lesions.

Methods

A literature search of relevant DWI studies was performed. The accuracy of DWI to characterize lesions by using b value ≤600 s/mm² and b value >600 s/mm² was presented as pooled sensitivity and specificity, and the ADC was calculated for both groups. Lesions were pooled as pre- or post-contrast DWI.

Results

Of 198 articles, 26 met the inclusion criteria. Median ADCs were significantly higher (13.2–35.1 %, p?b values ≤600 s/mm² compared to >600 s/mm². The sensitivity in both groups was similar (91 % and 89 %, p?=?0.495) as well as the specificity (75 % and 84 %, p?=?0.237). Contrast medium had no significant effects on the ADCs (p?≥?0.08). The differentiation between benign and malignant lesions was optimal (58.4 %) for the combination of b?=?0 and 1,000 s/mm².

Conclusions

The wide variety of b value combinations applied in different studies significantly affects the ADC of breast lesions and confounds quantitative DWI. If only a couple of b values are used, those of b?=?0 and 1,000 s/mm² are recommended for the best improvement of differentiating between benign and malignant lesions.

Key Points

? The choice of b values significantly affects the ADC of breast lesions. ? Sensitivity and specificity are not affected by the choice of b values. ? b values 0 and 1,000 s/mm ² are recommended for optimal differentiation between benign and malignant lesions. ? Contrast medium prior to DWI does not significantly affect the ADC.     

Ultrasound-guided infraclavicular versus supraclavicular block

In this prospective study we compared ultrasound-guided (USG) infraclavicular and supraclavicular blocks for performance time and quality of block. We hypothesized that the infraclavicular approach would result in shorter performance times with a quality of block similar to that of the supraclavicular approach. Eighty patients were randomized into two equal groups: Group I (infraclavicular) and Group S (supraclavicular). All blocks were performed using ultrasound visualization with a 7.5-MHz linear probe and neurostimulation. The anesthetic mixture consisted of 0.5 mL/kg of bupivacaine 0.5% and lidocaine hydrocarbonate 2% (1:3 vol.) with epinephrine 1:200,000. Sensory block, motor block, and supplementation rates were evaluated for the musculocutaneous, median, radial, and ulnar nerves. Surgical anesthesia without supplementation was achieved in 80% of patients in group I compared with 87% in Group S (P = 0.39). Supplementation rates were significantly different only for the radial territory: 18% in Group I versus 0% in group S (P = 0.006). Block performance times were not different between groups (4.0 min in Group I versus 4.65 min in Group S; P = 0.43). Technique-related pain scores were not different between groups (I: 2.0; S: 2.0; P = 1.00). We conclude that USG infraclavicular block is at least as rapidly executed as USG supraclavicular block and produces a similar degree of surgical anesthesia without supplementation.     

Digital rectal examination and the diagnosis of prostate cancer--a study based on 8 years and three screenings within the European Randomized Study of Screening for Prostate Cancer (ERSPC), Rotterdam

Background

Evidence indicates that an abnormal digital rectal examination (DRE) is a risk factor for high-grade prostate cancer (PC).

Objective

To determine whether men with an initially suspicious DRE, a prostate-specific antigen (PSA) level ≥3.0 ng/ml, and a benign prostate biopsy are at higher risk for significant PC at rescreening than men with an initially normal DRE, and whether an adaptation of the rescreening interval is warranted for this group.

Design, Setting, and Participants

Within the European Randomized Study of Screening for Prostate Cancer (ERSPC), Rotterdam, 2218 men underwent biopsy of the prostate (from 1993 to 2000) with a benign result at initial screening. The serum PSA was determined every 4 yr. A PSA level of ≥3.0 ng/ml prompted a DRE and a lateralised sextant biopsy.

Measurements

Number and characteristics of PCs found at repeat screenings and as interval cancers (ICs) were compared between men with or without a suspicious DRE result at initial screening. Multivariate logistic regression analyses were performed to evaluate if an initially suspicious DRE was a significant predictor for detecting cancer at consecutive screenings.

Results and Limitations

After 4 yr, the total number of PCs detected in men with and without an initially suspicious DRE was, respectively, 27 (6%) versus 103 (6%) (p = 0.99). After 8 yr these numbers increased, respectively, to,45 (10%) versus 167 (10%) (p = 0.88). The proportion of clinically significant PCs was 2% and 3%, respectively, for the group with initially normal and abnormal DRE after 8 yr. Having a suspicious DRE result at initial screening was not a significant predictor for detecting PC after 4 yr [odds ratio (OR) = 1.15, p = 0.59) or 8 yr (OR = 1.41, p = 0.43)]. A limitation of this study is the relatively short follow-up of 8 yr.

Conclusions

During a follow-up of 8 yr after initial cancer-negative biopsy, an initially suspicious DRE did not influence the chance for detection of cancer or significant cancer at later screens. An adaptation of the rescreening interval on the basis of the initial DRE-outcome is not warranted in future population-based screening for prostate cancer.     

Ultrasound guidance speeds execution and improves the quality of supraclavicular block

In this prospective study, we assessed the quality, safety, and execution time of supraclavicular block of the brachial plexus using ultrasonic guidance and neurostimulation compared with a supraclavicular technique that used anatomical landmarks and neurostimulation. It was hypothesized that ultrasonic guidance would increase the proportion of successful blocks, decrease block execution time, and reduce the incidence of complications such as pneumothorax and neuropathy. Eighty patients were randomized into two groups of 40, Group US (supraclavicular block guided in real time by a two-dimensional ultrasonic image, with neurostimulator confirmation of correct needle position) and Group NS (supraclavicular block using the subclavian perivascular approach, also with neurostimulator confirmation). Blocks were performed using bupivacaine 0.5% and lidocaine 2% (1:1 vol) with epinephrine 1:200000 as the anesthetic mixture. The onset of motor and sensory block for the musculocutaneous, median, radial, and ulnar nerves was evaluated over a 30 min period. At 30 min 95% of patients in Group US and 85% of patients in Group NS had a partial or complete sensory block of all nerve territories (P = 0.13) and 55% of patients in Group US and 65% of patients in Group NS had a complete block of all nerve territories (P = 0.25). Surgical anesthesia without supplementation was achieved in 85% of patients in Group US and 78% of patients in Group NS (P = 0.28). No patient in Group US and 8% of patients in Group NS required general anesthesia (P = 0.12). The quality of ulnar block was significantly inferior to the quality of block in other nerve territories in Group NS, but not in Group US; the quality of ulnar block was not significantly different between Groups NS and US. The block was performed in an average of 9.8 min in Group NS and 5.0 min in Group US (P = 0.0001). No major complication occurred in either group. We conclude that ultrasound-guided neurostimulator-confirmed supraclavicular block is more rapidly performed and provides a more complete block than supraclavicular block using anatomic landmarks and neurostimulator confirmation. IMPLICATIONS: Ultrasound-guided neurostimulator-confirmed supraclavicular block is more rapidly performed and provides a block of better quality than supraclavicular block using anatomic landmarks and neurostimulator confirmation.     

Familial medullary carcinoma prevention, risk evaluation, and RET in children of families with MEN2

The ability to predict the risk of MEN2 and medullary thyroid carcinoma (MTC) by genetic RET proto-oncogene analysis has provided an essential tool in identifying patients in whom thyroid cancer can be prevented by prophylactic thyroidectomy but emphasizes the need for clear policy guidelines. Children of families with RET cysteine mutations (exons 10, 11, 13, and 16) may develop early metastatic tumours and require prophylactic thyroidectomy. The 918 mutation associated with MEN2B is associated with early aggressive behaviour and distant metastatic spread. This has led to active screening of affected families underlining the need for specific intervention strategies.

Aim

To evaluate the risk to children of families with MEN2 and to assess the risk and determine the treatment.

Methods

Twenty-five patients from 10 families with MEN2 phenotypes were screened for RET mutations. Polymerase chain reaction amplification was performed on all 21 exons of the RET proto-oncogene, followed by heteroduplex single-strand conformation polymorphism (HEX-SSCP) analysis. Polymerase chain reaction products demonstrating variation in the HEX-SSCP gels were subjected to automated DNA sequencing analysis.

Results

Eleven significant RET mutations were detected in affected families. Eight index cases received initial thyroidectomy for established MTC (plus 2 advised). In the family members screened, 3 prophylactic thyroidectomies (2 with early MTC) were performed and a further 2 recommended. An exon 10 C620W missense mutation (the “Janus” gene) was detected in a patient with Hirschsprung's disease plus 1 family member.

Conclusion

RET analysis of MEN has revolutionized the management of children of families with MEN2 and allowed surgical prediction and prophylaxis to take place. The presence of an exon 10 C620W mutation in association with Hirschsprung's disease was difficult to assess. We suggest possible guidelines for management of families with MTC and the role of genetic testing in their evaluation.     

Effects of Intermittent Femoral Nerve Injections of Bupivacaine, Levobupivacaine, and Ropivacaine on Mitochondrial Energy Metabolism and Intracellular Calcium Homeostasis in Rat Psoas Muscle

Background: Long-acting local anesthetics cause muscle damage. Moreover, long-acting local anesthetics act as uncoupler of oxidative phosphorylation in isolated mitochondria and enhance sarcoplasmic reticulum Ca2+ release. The aim of the study was to evaluate effects of perineural injections of local anesthetics on mitochondrial energetic metabolism and intracellular calcium homeostasis in vivo.

Methods: Femoral nerve block catheters were inserted in adult male Wistar rats. Rats were randomized and received seven injections (1 ml/kg) of bupivacaine, levobupivacaine, ropivacaine, or isotonic saline at 8-h intervals. Rats were killed 8 h after the last injection. Psoas muscle was quickly dissected from next to the femoral nerve. Local anesthetic concentrations in muscle were determined. Oxidative capacity was measured in saponin-skinned fibers. Oxygen consumption rates were measured, and mitochondrial adenosine triphosphate synthesis rate was determined. Enzymatic activities of mitochondrial respiratory chain complexes were evaluated. Local calcium release events (calcium sparks) were analyzed as well as sarcoplasmic reticulum calcium content in saponin-skinned fibers.

Results: Eight hours after the last injection, psoas muscle concentration of local anesthetics was less than 0.3 [mu]g/g tissue. Adenosine triphosphate synthesis and adenosine triphosphate-to-oxygen ratio were significantly decreased in the muscle of rats treated with local anesthetics. A global decrease (around 50%) in all of the enzyme activities of the respiratory chain was observed. Levobupivacaine increased the amplitude and frequency of the calcium sparks, whereas lower sarcoplasmic reticulum calcium content was shown.     

Tattooing Breast Cancers Treated with Neoadjuvant Chemotherapy

Background In breast carcinomas treated with neoadjuvant chemotherapy, intraoperative identification of residual tumors may be difficult. A well-tolerated, low-diffusion charcoal suspension has been designed to tattoo breast tumors. In this study, we investigated whether this tattooing technique is efficient for localizing the tumor after treatment with chemotherapy. Methods In a series of 109 patients with large breast tumors, a 4% or 10% charcoal suspension was injected at the time of the initial biopsy before preoperative chemotherapy. Results Tolerance was good. After three or four cycles of chemotherapy, 91 patients underwent conservative treatment, and the surgical specimen was examined intraoperatively. The charcoal was detected in 94% of the cases. The charcoal was seen in the nodule or at the periphery in the surgical specimen without any acute inflammatory reaction or diffusion. Conclusions On the basis of these results, this micronized charcoal suspension at a defined granulometry and a concentration of 10% seems to be ideal for tattooing breast carcinomas over a period of 3 months in patients in whom neoadjuvant chemotherapy is planned.     

Persistent neuropathic pain after inguinal herniorrhaphy depending on the procedure (open mesh v. laparoscopy): a propensity-matched analysis

Background

A greater incidence of persistent pain after inguinal herniorrhaphy is suspected with the open mesh procedure than with laparoscopy (transabdominal preperitoneal), but the involvement of neuropathy needs to be clarified.

Methods

We examined the cumulative incidence of neuropathic persistent pain, defined as self-report of pain at the surgical site with neuropathic aspects, within 6 months after surgery in 2 prospective subcohorts of a multicentre study. We compared open mesh with laparoscopy using different analysis, including a propensity-matched analysis with the propensity score built from a multivariable analysis using a generalized linear model.

Results

Considering the full patient sample (242 open mesh v. 126 laparoscopy), the raw odds ratio for neuropathic persistent pain after inguinal herniorrhaphy was 4.3. It reached 6.8 with the propensity-matched analysis conducted on pooled subgroups of 194 patients undergoing open mesh and 125 undergoing laparoscopy (95% confidence interval 1.5–30.4, p = 0.012). A risk factor analysis of these pooled subgroups revealed that history of peripheral neuropathy was an independent risk factor for persistent neuropathic pain, while older age was protective.

Conclusion

We found a greater risk of persistent pain with open mesh than with laparoscopy that may be explained by direct or indirect lesion of nerve terminations. Strategies to identify and preserve nerve terminations with the open mesh procedure are needed.