The value of contrast-enhanced ultrasonography in the diagnosis of primary testicular non-neoplastic and neoplastic lesions in adults

doi:10.21203/rs.3.rs-2009835/v1

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The value of contrast-enhanced ultrasonography in the diagnosis of primary testicular non-neoplastic and neoplastic lesions in adults

https://doi.org/10.21203/rs.3.rs-2009835/v1

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Background: Different pathological types of testicular tumors are treated differently. For example, malignant germ cell tumors require radical orchiectomy, benign tumors only require mass enucleation and segmental infarction does not require treatment. Contrast-enhanced ultrasonography (CEUS) can more sensitively display tumor microvessels, thereby distinguishing between benign and malignant tumors.

Methods: This was a retrospective analysis of 35 patients with primary testicular non-neoplastic and neoplastic confirmed by pathology in our hospital from February 2017 to February 2022. Conventional ultrasonography and CEUS of primary testicular non-neoplastic lesions and neoplastic lesions of different pathological types in adults were retrospectively analyzed and their diagnostic values were compared with the pathological results.

Results: The sensitivity, specificity, positive predictive value, negative predictive value and accuracy rates for conventional ultrasound in the diagnosis of benign testicular tumors based on "onion skin-like" echo (epidermoid cysts) and peripheral annular blood flow were 30.8%, 100.0%, 100.0%, 71.9% and 75.0%, respectively. According to CEUS without enhancement (non-neoplastic lesions and epidermoid cysts) and uniform high enhancement with fast forward and slow backward (SLCT), the sensitivity, specificity, positive predictive value, negative predictive value and accuracy rates for diagnosing benign testicular tumors were 100.0%, 100.0%, 100.0%, 100.0% and 100.0%, respectively. Compared with conventional ultrasound, the difference was statistically significant (P=0.004).

Conclusions: CEUS could accurately distinguish between benign and malignant testicular tumors and also diagnosed specific pathological types (such as testicular focal infarction, epidermoid cysts, spermatocytic tumors, SLTC and lymphoma). Different pathological types of testicular tumors had different treatment options; thus, accurate preoperative diagnosis was of great significance and could guide the selection of appropriate treatment options.

Ultrasonography

Microbubbles

Hematoma

Testicular tumor

Pathology

Testicular tumors are the most common malignant tumors in adolescents and are classified into germ cell tumors (seminoma, embryonal carcinoma, yolk sac tumors, trophoblastic tumors, teratoma, mixed germ cell tumors, spermatocytic tumors and epidermoid cysts); sex cord-stromal tumors (Leydig cell tumors and Sertoli cell tumors) and some other rare types of tumors. Although there are many types of testicular tumors, most are germ cell tumors [1,2]. In the past, most testicular tumors were considered malignant (with seminomas being the most common) [3,4]. Needle biopsy can lead to local recurrence; therefore, this technique is generally not recommended for testicular tumors. Under the current treatment plan for testicular tumors, most testicular tumors (including benign ones) are subjected to radical orchiectomy which will inevitably lead to infertility, psychological problems and endocrine disorders [5]. Testicular non-neoplastic lesions (hematoma, necrosis), benign testicular tumors (Leydig cell tumors) and lymphoma do not require radical orchiectomy. Ultrasound has become the imaging modality of choice for scrotal disease [2,6], and can detect many small testicular masses, many of which are benign [7]. However, relative to the high sensitivity of ultrasound to detect testicular masses, the diagnostic specificity is low. If radical orchiectomy is performed, the testicles of many patients with testicular tumors are prone to be incised by mistake. In this study, we retrospectively analyzed conventional ultrasonography and contrast-enhanced ultrasonography (CEUS) of primary testicular non-neoplastic and neoplastic lesions in adults, in order to provide an accurate preoperative diagnosis to guide clinical treatment and avoid unnecessary orchiectomy.

Subjects

This was a retrospective analysis of 35 patients with primary testicular non-neoplastic and neoplastic confirmed by pathology in our hospital from February 2017 to February 2022. The inclusion criteria were as follows: (1) confirmed by histopathology or cytopathology, (2) with complete routine ultrasound and CEUS data, (3) ages ≥ 18 years. The exclusion criteria were as follows: (1) incomplete data, a lack of histological and pathological results and/or incomplete ultrasound images; (2) patient received non-steroidal anti-inflammatory drugs, radiotherapy, chemotherapy or other forms of immunotherapy, and (3) ages < 18 years.

According to the pathological results, patients were divided into five groups: a testicular non-neoplastic lesions (hematoma and necrosis) group, an epidermoid cyst group, a malignant germ cell tumor group, a Sertoli-Leydig cell tumor (SLCT) group, and a lymphoma group. Patients in the testicular non-neoplastic lesion group were aged 35.0 − 68.0 years (mean: 48.3 ± 17.4 years). Patients in the epidermoid cyst group were aged 24.0 − 28.0 years (mean: 25.6 ± 1.7 years); while those in the malignant germ cell tumor group were aged 25.0 − 66.0 years (mean: 40.6 ± 13.7 years). Patients in the SLCT group were aged 36.0 − 64.0 years (mean: 46.2 ± 12.6 years) while those in the lymphoma group were aged 55.0 − 67.0 years (mean: 60.3 ± 4.9 years). The patients in the epidermoid cyst were significantly younger than those in the other four groups (P < 0.05). Patients in the lymphoma group were significantly older than those in the epidermoid cyst group, the malignant germ cell tumor group and the SLTC group (P < 0.05); there was no statistical difference between the other groups (P > 0.05). The largest diameter of the lesions in the testicular non-neoplastic lesions group was 1.82.9 cm (mean: 2.2 ± 0.6 cm). This compared to 0.9 − 3.3 cm (mean: 2.0 ± 0.9 cm) in the epidermoid cyst group, 1.6 − 7.5 cm (mean: 4.4 ± 10.9 cm) in the malignant germ cell tumor group, 0.3 − 3.2cm (mean: 1.5 ± 1.1cm) in the SLCT group and 2.5 − 9.3cm (mean: 5.1 ± 2.1cm) in the lymphoma group. The SLCT group had significantly smaller lesions than the malignant germ cell tumor group and the lymphoma group (P < 0.05). The lymphoma group had the largest lesions which were significantly larger than those in the testicular non-neoplastic lesions group, the epidermoid cyst group and the SLCT group (P < 0.05). The size of the lesions in the malignant germ cell tumor group was significantly different from that in the epidermoid cyst group and the SLCT group (P < 0.05); there was no statistical difference between the other groups (P > 0.05).

Equipment and agents

The contrast agent used in CEUS was SonoVue (Bracco SpA, Milan, Italy). The agent consisted of microbubbles containing sulfur hexafluoride (SF 6) encapsulated in phospholipids. The microbubbles had a mean diameter of 2.5 µm and pH values of 4.5 − 7.5. The SonoVue powder was thoroughly dissolved in 5 mL of normal saline; then, 2.4 mL of the solution was injected into the bolus through the cubital vein.

The ultrasound devices used included the Aplio500 (TOSHIBA CORPORATION, Tokyo, Japan), LOGIQ E9 GE (General Electric Company, Boston, MA, USA), EPIQ7 (Philips Electronic N.V, Amsterdam, The Netherlands), EUB-8500 (HITACHI, Tokyo, Japan), and Aixplorer (SuperSonic Imagine, Aix-en-Provence, France). The CEUS function was available on all these devices. If the mass was small, then a linear array probe was selected with a frequency of 5.0 − 12.0 MHz. If the mass was large, then the linear array probe could not be fully displayed; instead, an abdominal convex array probe was used with a frequency of 3.0 − 5.0 MHz.

Methodology

Conventional ultrasound and CEUS images of the primary testicular non-neoplastic and neoplastic lesions were retrospectively analyzed. The parameters of the conventional ultrasound images included the location, number, size, shape, echo, boundary, and color doppler flow imaging (CDFI). "Onion skin-like" echo was used as a diagnostic criterion for epidermoid cysts. Peripheral annular blood flow was used as the diagnostic criterion for SLCT and perforating vessels were used as the diagnostic criteria for lymphoma; other cases were diagnosed as malignant germ cell tumors. The findings were interpreted by two physicians with 10 years of experience in scrotal ultrasound and each preliminary diagnosis was made after the physicians reached an agreement. The parameters of CEUS included the enhancement time, enhancement level (high, equal, low, or none) and contrast-agent distribution (uniform or non-uniform). Non-enhancement on CEUS was used as a diagnostic criterion for testicular non-neoplastic lesions and epidermoid cysts. CEUS showing uniform high enhancement with fast forward and fast backward was used as the diagnostic criterion for SLCT. CEUS showing uniform hyperenhancement with fast forward and fast backward was used as the diagnostic criterion for lymphoma. CEUS showing heterogeneous enhancement was used as the diagnostic criterion for malignant germ cell tumors of the testis. The findings were interpreted by two physicians with five years of experience in scrotal ultrasound and each preliminary diagnosis was made after the physicians reached an agreement. All four physicians were blinded to the final diagnoses and other imaging information at the time of image interpretation and preliminary diagnoses.

Statistical analysis

Statistical analysis was performed using the SPSS 20.0 software package (Chicago, IL, USA). Count data were analyzed using the paired χ² test and the diagnostic accuracy of the examinations was assessed by 2-by-2 tables. Measurement data were expressed as the mean ± SD. One-way analysis of variance (ANOVA) was used for comparisons among multiple groups and the LSD-t test was used for comparison between groups. A P value < 0.05 was considered statically significant.

1. Clinicopathological data

(1) Pathological results: We included 35 patients with 36 masses. Except for one case of bilateral testicular lymphoma, the others were single; 20 cases were in the right testis and 15 cases were in the left testis. All 36 cases of primary testicular lesions were confirmed by surgery or needle biopsy or by cytological pathology. There were three cases of testicular non-neoplastic lesions (one case of spontaneous hematoma, two cases of segmental infarctions); 33 cases of testicular neoplastic lesions (five cases of epidermoid cysts, 10 cases of seminomas, one case of embryonal carcinoma, two cases of mixed germ cell tumors, two cases of spermatocytic tumors, eight cases of primary lymphomas, two cases of Sertoli cell tumors and three cases of Leydig cell tumors).

(2) Clinical manifestations: Two cases of epidermoid cysts and two cases of Leydig cell tumors were asymptomatic; there was one case of spontaneous hematoma and two cases of segmental infarction showed dull pain in the testis. The remaining cases were all due to scrotal enlargement (one lymphoma and one epidermoid cyst with scrotal pain, the rest were painless enlargement).

(3) Laboratory examinations: AFP and HCG were elevated in two mixed germ cell tumors, HCG was elevated in one seminoma, AFP was elevated in one embryonal carcinoma, and follicle-stimulating hormone and luteinizing hormone were elevated in one bilateral lymphoma. No obvious related abnormalities were detected.

2. Findings of conventional ultrasound and CEUS

(1) Testicular non-neoplastic lesions group: Two cases were hypoechoic, one case was isoechoic; two cases had unclear borders, one case had clear borders; one case was round, two cases were irregular; one case had a small amount of testicular hydrocele; CDFI showed no obvious blood flow signal. Because there was no trauma and other related medical history, conventional ultrasonography was unable to make a clear diagnosis in two cases, and one case was malignant (Figs. 1,2). CEUS showed no enhancement in all three cases (Figs. 1,2) leading to the possibility of segmental infarction or spontaneous hematoma.

(2) Epidermoid cysts group: All five cases showed round-like and uneven echoes with clear boundaries, one case showed typical "onion skin-like" echoes and epidermoid cysts were clearly diagnosed; two cases showed peripheral coarse calcifications (Fig. 3) and two cases showed spot-like strong echoes. CDFI showed that except one case with no blood flow signal (diagnosed as an epidermoid cyst due to an "onion skin-like" echo), the other four cases showed blood flow signals (possibly a twinkle artifact) and were diagnosed as malignant tumors by conventional ultrasonography (Fig. 3). CEUS showed no enhancement in five cases (Fig. 3) and epidermoid cysts were diagnosed.

(3) Malignant germ cell tumor group: Two cases showed solid predominant cystic and solid mixed echoes, one case was isoechoic, and the rest were hypoechoic; two cases had unclear borders and the rest had clear borders; two cases had irregular shapes, and the rest were round or oval; three cases had bilateral testicular microlithiasis and two cases had bilateral testicular hydrocele. CDFI: Except for 1 case of embryonal carcinoma with poor blood flow signals (Fig. 4), the others all showed rich blood flow signals (Figs. 5,6). Of these, five cases showed perforating vessels which tended to be diagnosed as lymphoma; the rest were considered to be malignant, although the specific pathological type could not be determined. CEUS showed that 10 cases had heterogeneous high enhancement, with necrotic areas inside (Figs. 4,5). With regards to fast forward and fast backward; three cases showed uniform high enhancement (two cases with fast forward and fast backward, one case with fast forward and slow backward). Heterogeneous hyperenhancement can be considered characteristic of malignant germ cell tumors. Two cases of spermatogenic tumors showed sparse and low enhancement and one case showed a large area without enhancement (Fig. 6). Spermatogenic tumors were the only tumors with sparse and low enhancement among all the enhanced tumors; this could be regarded as its characteristic imaging appearance.

(4) SLCT group: Three cases were hypoechoic and two cases were isoechoic; all showed a clear boundary and a round mass; one case had a small amount of ipsilateral testicular hydrocele. CDFI: five cases showed abundant blood flow signals, of which three cases showed peripheral annular blood flow (Fig. 7). In this study, peripheral annular blood flow was only seen in SLCT; this can therefore be regarded as its characteristic imaging appearance, leading to a diagnosis of SLCT. CEUS had characteristic features: all showed uniform high enhancement (no necrotic area) (Fig. 7), fast forward and slow backward.

(5) Lymphoma group: All cases were hypoechoic with a clear boundary; three cases were irregular in shape, five cases were round or oval; one case had a small amount of bilateral testicular hydrocele. CDFI: eight cases showed abundant blood flow signals (Fig. 8), three of which were diagnosed as lymphoma due to perforating vessels; the rest were similar to malignant germ cell tumors, which were difficult to identify. CEUS: Except for one case with high enhancement and significant necrosis (perforating vessels in CDFI), the rest showed uniform high levels of enhancement (Fig. 8), fast forward and fast backward. Lymphoma was considered if the mass was larger and no necrotic areas were evident, comprehensive fast forward and fast backward, the patient was of older age and there were other manifestations (negative for tumor markers).

The sensitivity, specificity, positive predictive value, negative predictive value and accuracy rates of conventional ultrasound for the diagnosis of benign testicular tumors based on "onion skin-like" echo (epidermoid cysts) and peripheral annular blood flow were 30.8%, 100.0%, 100.0%, 71.9% and 75.0%, respectively. According to CEUS without enhancement (non-neoplastic lesions and epidermoid cysts) and uniform high enhancement with fast forward and slow backward (SLCT), the sensitivity, specificity, positive predictive value, negative predictive value and accuracy rates for diagnosing benign testicular tumors were 100.0%, 100.0%, 100.0%, 100.0% and 100.0%, respectively. Compared with conventional ultrasound, these differences were statistically significant (P = 0.004).

Most testicular tumors are malignant germ cell tumors [3,4]; thus, biopsy is generally not an option for testicular tumors this technique can lead to a higher recurrence rate. Therefore, radical orchiectomy is generally performed directly for testicular tumors, which will inevitably lead to some benign tumors and lymphomas being mistakenly cut from the testis. Non-neoplastic lesions of the testis generally do not require surgery. Benign tumors of the testis generally only require tumor enucleation, while lymphoma requires a comprehensive treatment that does not require surgery, mainly involving chemotherapy and radiotherapy. Therefore, the pathological diagnosis of testicular tumors by preoperative ultrasound (and not just a diagnosis as being benign or malignant) is of significant value in guiding surgery and preserving the testis of some patients. In this study, we found that CEUS accurately identified benign and malignant testicular lesions and also allowed the preliminary diagnosis of different pathological types of testicular tumors, including testicular focal infarction, epidermoid cysts, spermatogenic tumors, SLTC and lymphoma.

1. Testicular non-neoplastic lesions

Testicular non-neoplastic lesions include some focal infarcts and hematomas. The diagnosis of testicular hematoma is easier in the presence of a history of testicular trauma. However, a spontaneous testicular hematoma without a history of trauma is difficult to diagnose and is easily misdiagnosed as a testicular tumor [8]. In this study, one case of spontaneous hematoma had dull pain in the testis after bathing. Conventional ultrasound identified irregular hypoechoic signals in the right testis. Because there was no history of trauma, this was considered to be a malignant tumor. CEUS showed no enhancement in the mass and a diagnosis of spontaneous hematoma was made. Ultrasound-guided aspiration was used to draw out blood and the mass was gradually absorbed and reduced during ultrasound follow-up; this was consistent with changes associated with a hematoma. Testicular necrosis resulting from complete testicular torsion is relatively easy to diagnose [9]. Focal testicular necrosis secondary to a history of orchitis or vascular injury can also be diagnosed by ultrasonography [10,11]. Spontaneous testicular segmental infarcts are easily misdiagnosed as tumors in the absence of a relevant medical history, thus leading to unnecessary surgical resection [12–14]. In this study, two cases of segmental infarction showed solid echoes on conventional ultrasound. Because there was no relevant medical history, conventional ultrasound could not determine whether these were tumors or not. CEUS showed no enhancement, consistent with typical infarction. Due to the large infarct size, the infarct was resected. Therefore, for a spontaneous hematoma or segmental infarction with solid echoes on ultrasound, CEUS typically shows no enhancement, and can be clearly diagnosed as a non-neoplastic lesion, thereby avoiding unnecessary surgery.

(2) Testicular epidermoid cysts

Testicular epidermoid cysts are a rare form of benign tumor that account for only 2.1% of all testicular tumors [15]. In recent years, testicular epidermoid cysts have been classified as prepubertal teratomas [16]. Usually these are asymptomatic or represent a palpable painless testicular mass. Unlike testicular malignancies, epidermoid cysts can be cured with only local excision [17]. However, it is still difficult to differentiate epidermoid cysts from malignant testicular tumors on imaging [18]. The conventional ultrasound appearance of a typical epidermoid cyst is an "onion skin-like" echo [19] with a well-defined circular non-homogeneous echo with no blood flow signals on CDFI. In this study, only one case was diagnosed with an epidermoid cyst due to an "onion skin-like" echo (no blood flow signal was seen). The remaining four cases were diagnosed as malignant tumors by conventional ultrasonography because of internal blood flow signals (possibly misdiagnosing the ‘twinkling artifact’ as blood flow). The “twinkling artifact” tends to occur behind irregular crystals (epidermoid cysts contain keratin and cholesterol crystals). If CEUS shows no enhancement, then the diagnosis is an epidermoid cyst. CEUS can help inexperienced sonographers identify twinkling artifacts to accurately diagnose epidermoid cysts and perform testicular-sparing local excision of the mass.

(3) Malignant germ cell tumors.

Malignant germ cell tumors mainly include seminomas, embryonal carcinomas, spermatocytic tumors and mixed germ cell tumors. Such tumors account for most testicular tumors and require radical orchiectomy [1,4]. In this study, we found that malignant germ cell tumors were larger in size; this was due to their rapid growth rate. These are difficult to detect when tumors are small in the early stages; they can only be detected when tumors have undergone enlargement. The main clinical manifestation is painless swelling of the scrotum; however, this is also a common feature of testicular tumors and has no specificity. Studies have shown that AFP and HCG have certain values in the judgment of testicular tumor types [1,3], Seminomas and spermatocytic tumors generally express normal tumor markers and a small number of seminomas have slightly elevated levels of HCG. AFP is known to be elevated in embryonal carcinomas and yolk sac tumors. This study showed that one case of seminoma had elevated HCG, one case of embryonal carcinoma had elevated AFP, and two cases of mixed germ cell tumors had elevated AFP and HCG (both cases featured embryonic carcinoma, yolk sac, and seminoma). It has been suggested that AFP and HCG have a certain value for embryonal carcinoma and mixed germ cell tumors but have limited value for most seminomas and spermatocytic tumors; however, seminoma is the most common form of testicular tumor. Malignant germ cell tumors show malignant features on conventional ultrasound (mostly with well-circumscribed hypoechoic and rich blood flow signals) but have similarities with lymphomas and SLCT. All cases in this group were diagnosed as malignant by conventional ultrasound, although the specific type was difficult to identify. Of these, five cases with malignant germ cell tumors showed perforating vessels; these tended to be diagnosed as lymphoma. Because of the obvious necrosis of embryonal carcinomas and mixed germ cell tumors, CEUS showed heterogeneous hyperenhancement. Furthermore, obvious necrotic areas were seen inside; this differed from lymphoma and SLCT. Seven cases of seminoma showed heterogeneous enhancement, and three cases of uniform hyperenhancement were easily misdiagnosed as lymphoma. The age of the patients with such homogeneously enhanced seminoma did not exceed 48 years, and the median age of patients with primary testicular lymphomas was approximately 70 years [20]. The minimum age of the lymphoma patients in this group was 55 year. Thus, age can be used as a distinguishing feature. Spermatocytic tumors are a rare form of malignancy and account for 0.61% of all testicular germ cell tumors [21]. Spermatocytic tumors and seminomas have similar cytological appearances; thus, it is difficult to differentiate between seminoma and lymphoma with conventional ultrasound [22]. However, the performance of CEUS is different. Spermatocytic tumors are the only tumors with sparse and low enhancement (with obvious necrotic areas within) among all forms of enhanced tumors and can be regarded as the characteristic manifestation of spermatocytic tumors. This manifestation of spermatocytic tumors is related to myxoid degeneration, edema, hemorrhage and necrosis [23].

(4) SLCT

Most SLCTs are benign tumors [24]. To preserve the endocrine function of the testis, the general choice of treatment is enucleation of the testicular mass [25,26]. Tumors are generally small, asymptomatic and are mostly detected by ultrasonography. A small number of patients present with gynecomastia and infertility although when tumors are larger, they present with painless enlargement of the scrotum [27,28]. In this study, no endocrine symptoms were detected in five cases (testosterone and estradiol assays were not performed), three cases were referred for a painless testicular mass, and two cases were found incidentally by ultrasound. Ultrasound findings were well-defined, round-like, isoechoic or hypoechoic, with abundant blood flow, similar to those of lymphoma and seminoma. In our study, peripheral annular blood flow was only seen in SLCT; therefore, this can be regarded as a characteristic manifestation. Accordingly, three cases were diagnosed with SLCT. CEUS has characteristic manifestations: all patients showed uniform high enhancement without necrosis, fast forward and slow backward. Comprehensive judgment can be made in combination with testosterone and estradiol measurements [28,29].

(5) Testicular lymphoma

Primary testicular lymphomas are a rare form of extranodal lymphoma that accounts for 1 − 9% of all testicular malignancies [30,31]. The age of onset is generally over 50 years and the median age at diagnosis of primary testicular lymphoma was reported to be 70 years [20]. The clinical manifestation was painless enlargement of the scrotum; this was a consistent observation throughout this study. Lymphoma requires ultrasound-guided needle biopsy for diagnosis, followed by comprehensive treatment with chemotherapy and radiotherapy. Conventional ultrasonography of testicular lymphoma presents as a well-demarcated, round-like hypoechoic region with abundant blood flow. This condition can be easily misdiagnosed as seminoma. It has been reported in the literature that perforating vessels (testicular long blood vessels run normally in the mass) have certain value in the diagnosis of testicular lymphoma [32]. However, in this study, only 37.5% (3/8) of lymphomas had perforating vessels, and five cases of malignant germ cell tumors had perforating vessels; thus, the diagnostic value of these perforating vessels is limited. With regards to c-enhanced ultrasound, except for one case with high enhancement and significant necrosis (perforating vessels in CDFI), the remaining cases showed uniform high enhancement (with no necrotic areas), fast forward and fast backward. Testicular lymphoma was considered if the mass was larger and no necrotic area was evident, fast forward and fast rewind, older age and negative tumor markers.

The present study had some limitations that needed to be considered. First, this was a single-center retrospective study with a small sample size; further research with a multi-center design and a large sample size is now required. Second, this study was limited by its retrospective design and differences in matched models; we did not perform CEUS-based quantitative analysis. Third, the testicular lesions selected in this study were accompanied by pathological results. Therefore, many suspected non-neoplastic testicular lesions that did not undergo surgery were not included; this may have led to some selection bias. Fourth, because of the extremely high accuracy of the diagnosis of testicular tumors by the professional andrology sonographers in our center, they have won the trust of andrologists. Most testicular tumors have not undergone magnetic resonance examination; consequently, there is no other images available for comparative analysis.

In conclusion, CEUS could accurately distinguish between benign and malignant testicular tumors and could diagnose specific pathological types (such as testicular focal infarction, epidermoid cysts, spermatocytic tumors, SLTC and lymphomas). Different pathological types of testicular tumors had different treatment options. Accurate preoperative diagnosis was of great significance and could guide the surgical selection of appropriate treatment options.

Ethics approval and consent to participate

Authors reporting experiments on humans and/or the use of human tissue samples must confirm that all experiments were performed in accordance with relevant guidelines and regulations. A ll methods were carried out in accordance with relevant guidelines and regulations. All experimental protocols were approved by Ethics Committee of The First Ningbo Hospital. This retrospective study was approved by the Ethics Committee of The First Ningbo Hospital (Reference: 2021RS105). Informed consent was obtained from all subjects and/or their legal guardian(s).

Consent for publication: Not applicable.

Availability of data and materials: All data generated or analysed during this study are included in this published article.

Competing interests: The authors declare that they have no competing interests.

Funding: Not applicable.

Authors' contributions: (I) Conception and design: S Zhang, N Xue and G Wang; (II) Administrative support: S Zhang; (III) Provision of study materials or patients: N Xue, S Zhang and G Wang; (IV) Collection and assembly of data: N Xue; (V) Data analysis and interpretation: S Zhang, N Xue and G Wang; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

Acknowledgements: Not applicable.

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No competing interests reported.

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Reviewers invited by journal
08 Sep, 2022
Editor assigned by journal
01 Sep, 2022
Editor invited by journal
01 Sep, 2022
Submission checks completed at journal
01 Sep, 2022
First submitted to journal
29 Aug, 2022

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The value of contrast-enhanced ultrasonography in the diagnosis of primary testicular non-neoplastic and neoplastic lesions in adults

Status:

Version 1

Abstract

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Introduction

Methods

Subjects

Equipment and agents

Methodology

Statistical analysis

Results

Discussion

(4) SLCT

Declarations

References

Additional Declarations

Status:

Version 1