Near-infrared fluorescence-assisted superficial inguinal lymph-node excision for low-risk penile cancer.

OBJECTIVE: Identification of superficial inguinal lymph nodes during low-risk penile cancer surgery using near-infrared (NIR) fluorescence to improve the accuracy of lymph-node dissection and reduce the incidence of missed micrometastases and complications. METHODS: Thirty-two cases were selected, which were under the criteria of < T1, and no lymph-node metastasis was found with magnetic resonance imaging (MRI) detection. Two groups were randomly divided based on the fluorescence technique, the indocyanine green (ICG) group and the non-ICG group. In the ICG group, the ICG preparation was subcutaneously injected into the edge of the penile tumor 10 min before surgery, and the near-infrared fluorescence imager was used for observation. After the lymph nodes were visualized, the superficial inguinal lymph nodes were removed first, and then, the penis surgery was performed. The non-ICG group underwent superficial inguinal lymph-node dissection and penile surgery. RESULTS: Among the 16 patients in the ICG group, we obtained 11 lymph-node specimens using grayscale values of images (4.13 ± 0.72 vs. 3.00 ± 0.82 P = 0.003) along with shorter postoperative healing time (7.31 ± 1.08 vs. 8.88 ± 2.43 P = 0.025), and less lymphatic leakage (0 vs. 5 P = 0.04) than the 16 patients in the non-ICG group. Out of 11, 3 lymph nodes that are excised were further grouped into fluorescent and non-fluorescent regions (G1/G2) and found to be metastasized. CONCLUSION: Near-infrared fluorescence-assisted superficial inguinal lymph-node dissection in penile carcinoma is accurate and effective, and could reduce surgical complications.

Improved outcome in penile cancer with radiologically enhanced stratification protocol for lymph node staging procedures: a study in 316 inguinal basins with a mean follow-up of 5 years.

BACKGROUND: Lymph node metastasis is the main determinant of survival in penile cancer patients. Conventionally clinical palpability is used to stratify patients to Inguinal Lymph node dissection (ILND) if clinically node positive (cN +) or Dynamic sentinel node biopsy (DSNB) if clinically node negative (cN0). Studies suggest a false negative rate (FNR) of around 10% (5-13%) for DSNB. To our knowledge there are no studies reporting harder end point of survival and outcomes of all clinically node positive (cN +) patients. We present our outcome data of all patients with penile cancer including false negative rates and survival in both DSNB and ILND groups. METHODS: One hundred fifty-eight consecutive patients (316 inguinal basins), who had lymph node surgery for penile cancer in a tertiary referral centre from Jan 2008 to 2018, were included in the study. All patients underwent ultrasound (US) ± fine needle aspiration cytology (FNAC) and then MRI/ CT, if needed, to stage their disease. We used combined clinical and radiological criteria (node size, architecture loss, irregular margins) to stratify patients to DSNB vs ILND as opposed to clinical palpability alone. RESULTS: 11.2% i.e., 27/241 inguinal basins had lymph node positive disease by DSNB. 54.9% i.e., 39/71 inguinal basins (IBs) had lymph node-positive disease by ILND. 4 inguinal basins with no tracer uptake in sentinel node scans are being monitored at patient's request and have not had any recurrences to date. With a mean follow-up of 65 months (range 24-150), the false-negative rate (FNR) for DSNB is 0%. Judicious uses of cross-sectional imaging necessitated ILND in 2 inguinal basins with non-palpable nodes and negative US with false positive rate of 6.3% (2/32) for ILND. The same cohort of DSNB patients might have had 11.1% (3/27) FNR if only palpability criteria was used. 43 (28%) patients who did require cross sectional imaging as per our criteria had a low node positive rate of 4.7% (p = 0.03). Mean cancer specific survival of all node-positive patients was 105 months. CONCLUSION: The performance of DSNB improved with enhanced radiological stratification of patients to either DSNB or ILND. We for the first time report the comprehensive outcome of all lymph node staging procedures in penile cancer.

Diagnostic Accuracy of MRI in Local Staging (T Category) of Penile Cancer and the Value of Artificial Erection: A Systematic Review and Meta-Analysis.

BACKGROUND. Treatment recommendations of penile cancers are determined primarily by the local extent of the primary tumor. Clinical palpation is used for local staging. OBJECTIVE. We reviewed diagnostic performance of MRI in local staging of penile cancer in three clinical scenarios (questions [Qs] 1 through 3, Q1-Q3) and one imaging scenario (Q4). Q1 asked whether MRI reliably distinguishes ≤ T1 from ≥ T2 disease. Q2 asked whether clinical staging reliably identifies ≤ T1 versus ≥ T2 disease and how clinical staging compares to MRI. Q3 asked if MRI is accurate for diagnosis of T3 disease. Q4 asked if artificial erection (by intracavernosal injection of prostaglandin E1) improved accuracy of MRI in T categorization. EVIDENCE ACQUISITION. MEDLINE, EMBASE, and Cochrane Library databases were searched through September 13, 2021, for studies evaluating local staging of penile cancer using MRI with surgical pathology as the reference standard. Diagnostic accuracy was calculated using a bivariate random-effects model and hierarchic summary ROC mode Meta-regression was performed to test for covariate effects of MRI and artificial erection in Q3 and Q4, respectively. EVIDENCE SYNTHESIS. Eight studies and 481 patients were included. The sensitivity and specificity of MRI for Q1 were 86% (95% CI, 73-94%) and 89% (95% CI, 77-95%), respectively. AUC for MRI (0.94; 95% CI, 0.92-0.96) did not differ from clinical staging (0.87; 95% CI, 0.84-0.90; p = .83). For Q3, MRI had sensitivity and specificity of 80% (95% CI, 70-87%) and 96% (95% CI, 85-99%), respectively. For Q4, sensitivity and specificity for MRI with versus without artificial erection were 85% (95% CI, 71-92%) and 93% (95% CI, 77-98%) versus 86% (95% CI, 68-95%) and 84% (95% CI, 70-93%), respectively (p = .50). CONCLUSION. MRI staging of penile cancer may be considered for ≤ T1 versus ≥ T2 disease but did not appear more accurate than clinical staging. High specificity of MRI for diagnosis of ≥ T3 disease suggests that MRI may be useful when organ-sparing approaches are planned. MRI with and without artificial erection showed similar accuracy in local staging. CLINICAL IMPACT. MRI, with or without artificial erection, may be valuable in routine preoperative evaluation of local staging of penile cancer, particularly when organ-sparing options are considered.

Myointimoma (angiocentric myofibroblastic tumor) of the glans penis in an adolescent: a case report and review of the literature.

BACKGROUND: Soft tumors of the penis are extremely rare in childhood and adolescence. Because there are no guidelines, each such case raises embarrassment over the extent and degree of aggressiveness of the diagnostic and therapeutic procedures. Herein, we describe a case of a teenager with a penile myointimoma along with a review of the literature. So far, only 10 cases have been reported in this age group. CASE PRESENTATION: The 15-year-old boy presented with a 6-months history of a slowly growing, palpable firm nodule in glans penis. Physical examination revealed a palpable, well circumscribed, firm, whitish painless mass, around 1 cm in diameter within the glans. Ultrasound revealed hypoechogenic, hypoperfused poorly defined area inside the glans. MRI did not confirm any other pathologic mass inside the glans and corpora cavernosa. An excisional biopsy was performed; its immunohistological features indicated myointimoma. DISCUSSION AND CONCLUSION: Given the rarity of this benign entity, the main importance is to distinguish myointioma from more clinically aggressive neoplasms. The key to a correct diagnosis is a careful histological examination, including immunohistochemistry. Local excision is safe and effective treatment modality.

[A Case of Multiple Penile Schwannoma].

A 48-year-old man presented with a painless nodule on the right ventral aspect of the penile shaft root. The patient visited the hospital and complained that the mass was growing. On physical examinations, a 5 cm mass without tenderness was palpated. An isoechoic mass about 4 cm in size was observed on ultrasonography. Inhomogeneous high signal intensity was observed on T2-weighted magnetic resonance imaging. A needle biopsy revealed schwannoma. During surgery for excision of the tumor, another small tumor was detected both tumors were resected. Both tumors were diagnosed as schwannoma by pathological examination. Out of 40 cases of penile schwannoma reported, eight were of multiple tumors. In our case, it was difficult to detect the other small tumor by preoperative diagnosis. Therefore, we recommend careful observation during surgery.

Role of MRI in Staging of Penile Cancer.

Penile cancer is one of the male-specific cancers. Accurate pretreatment staging is crucial due to a plethora of treatment options currently available. The 8th edition American Joint Committee on Cancer-Tumor Node and Metastasis (AJCC-TNM) revised the staging for penile cancers, with invasion of corpora cavernosa upstaged from T2 to T3 and invasion of urethra downstaged from T3 to being not separately relevant. With this revision, MRI is more relevant in local staging because MRI is accurate in identifying invasion of corpora cavernosa, while the accuracy is lower for detection of urethral involvement. The recent European Urology Association (EAU) guidelines recommend MRI to exclude invasion of the corpora cavernosa, especially if penis preservation is planned. Identification of satellite lesions and measurement of residual-penile-length help in surgical planning. When nonsurgical treatment modalities of the primary tumor are being considered, accurate local staging helps in decision-making regarding upfront inguinal lymph node dissection as against surveillance. MRI helps in detection and extent of inguinal and pelvic lymphadenopathy and is superior to clinical palpation, which continues to be the current approach recommended by National Comprehensive Cancer Network (NCCN) treatment guidelines. MRI helps the detection of "bulky" lymph nodes that warrant neoadjuvant chemotherapy and potentially identify extranodal extension. However, tumor involvement in small lymph nodes and differentiation of reactive vs. malignant lymphadenopathy in large lymph nodes continue to be challenging and the utilization of alternative contrast agents (superparamagnetic iron oxide), positron emission tomography (PET)-MRI along with texture analysis is promising. In locally recurrent tumors, MRI is invaluable in identification of deep invasion, which forms the basis of treatment. Multiparametric MRI, especially diffusion-weighted-imaging, may allow for quantitative noninvasive assessment of tumor grade and histologic subtyping to avoid biopsy undersampling. Further research is required for incorporation of MRI with deep learning and artificial intelligence algorithms for effective staging in penile cancer. Level of Evidence: 5 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2020;51:1612-1629.

Anatomical characterization of the inguinal lymph nodes using microcomputed tomography to inform radical inguinal lymph node dissections in penile cancer.

BACKGROUND & OBJECTIVES: Radical inguinal lymph node dissections (rILND) for penile cancer risk significant postoperative lymphocele and lymphedema. However, reducing the risk of lymphatic complications is limited by our understanding of lymphatic anatomy. Therefore, this study aims to elucidate the lymphatic anatomy within the current surgical borders of a rILND. METHODS: To visualize the position of the lymph nodes, tissue packets excised from the inguinal region of five fresh, male cadavers were imaged using microcomputed tomography (µCT). To standardize the position, rotation and size between specimens, each lymph node packet was aligned using a Generalized Procrustes analysis. RESULTS: There was a median of 13.5 lymph nodes (range = 8-18) per packet, with the majority (99%) clustered within a 6 cm radius of the saphenofemoral junction; a region 39%-41% smaller than current surgical borders. No difference existed between the number of nodes between sides, or distribution around the saphenofemoral junction. CONCLUSIONS: This study provides the first 3D, in situ, standardized characterization of lymph node anatomy in the inguinal region using µCT. By using knowledge of the normal lymphatic anatomy, this study can help inform the reduction in borders of rILND to limit disruption and ensure a complete lymphadenectomy.

A Review of Viral-Related Malignancies and the Associated Imaging Findings.

OBJECTIVE. Imaging plays an important role in the diagnosis and staging of malignancies. Many common lymphoproliferative and other solid tumor malignancies can be viral-related. CONCLUSION. This review discusses the imaging findings that can be associated with common viral-induced malignancies. Knowledge of these imaging presentations can help narrow the differential diagnosis to reach a specific diagnosis through a precise workup and proper management.

18F-FDG PET/CT as a prognostic factor in penile cancer.

PURPOSE: Penile cancer (PC) is a rare neoplasm with an aggressive behavior and variable prognosis. Lymph node (LN) involvement and pathological features of the primary lesion have been proven to be the most important survival factors. Positron emission tomography/computed tomography with fluorodeoxyglucose labelled with fluorine-18 (18F-FDG PET/CT) provides information on tumor staging and works as a prognostic factor, with promising results in other carcinomas. The aim of the present study is to evaluate PET/CT as a prognostic factor in PC. METHODS: Fifty-five patients (mean age 56.6 y) diagnosed with penile squamous cell carcinoma were prospectively evaluated from 2012 to 2014. All subjects underwent 18F-FDG PET/CT before treatment and were regularly followed after surgery. RESULTS: Out of the 53 patients selected, 17 (32.1%) had localized disease (cT1-2) and 24 (45.3%) had palpable nodes (cN+). Partial penile amputation was performed in 38 patients (71.7%) and inguinal lymphadenectomy (LND) in 30 (56.6%). From the LND group, 16 (53.3%) presented with positive neoplastic cells (pN+). Patients with more aggressive disease had a significantly (p = 0.019) higher 18F-FDG tumor uptake (pSUVmax), while inguinal LN uptake (nSUVmax) was able to recognize metastatic LN (p = 0.039). Some pathological prognostic features, when presented, have shown significant changes in pSUVmax values. Receiver operating characteristic (ROC) curves were performed and specific cutoff values of pSUVmax were evaluated to determine sensitivity and specificity. Regarding regional LNs, PET/CT presented a 76.2% accuracy in cN+ patients. After a 39-month follow up, pSUVmax of 16.6 (p = 0.0001) and nSUVmax of 6.5 (p = 0.019) were established as the ideal values to predict cancer-specific survival. The multivariate analysis confirmed nSUVmax as a predictor for LN metastasis (p = 0.043) and pSUVmax as a mean to estimate survival rate (p = 0.05). CONCLUSION: This study showed promising results on the use of 18F-FDG PET/CT as a prognostic tool for PC, using specific cutoff values of pSUVmax and nSUVmax.

Recent developments in penile cancer imaging.

PURPOSE OF REVIEW: This review discusses new findings in penile cancer imaging in relation to the European Association of Urology and National Comprehensive Cancer Network guidelines. RECENT FINDINGS: For imaging in penile cancer patients who are candidates for organ-sparing primary treatment, ultrasound with Doppler seems to be the method of choice in addition to physical examination. The sentinel node biopsy (SNB) procedure is used to detect small nodal metastases in clinically node-negative patients. In recent years, this procedure has been enhanced by 3D imaging using single photon emission computed tomography (SPECT) with computed tomography (CT) to improve preoperative localization and interpretation of sentinel nodes, as well as hybrid fluorescent and radioactive tracers to increase intraoperative localization of sentinel nodes. 18F-fluorodeoxyglucose PET (FDG-PET) with CT appears to be mainly useful for pelvic and distant staging in clinically node-positive patients. Other modalities with a potential future role in penile cancer are ultrasound with shear wave elastography, FDG-PET with MRI and ultrasmall paramagnetic iron oxide-enhanced MRI. SUMMARY: Imaging modalities in penile cancer have advanced throughout the years, assisting in treatment decision-making and during invasive procedures.

[A Case of Sarcomatoid Squamous Cell Carcinoma of the Penis].

A 74-year-old man presented to our hospital with the swelling of penis in May 2016. Physical examination revealed a goose egg-sized lump at the tip of the penis under foreskin. After dorsal skin incision we confirmed the 7 cm tumor on the inner preputial skin and then resected the tumor with circumcision. Histopathological examination revealed sarcomatoid squamous cell carcinoma of the penis. Computed tomography (CT) revealed swelling of bilateral inguinal lymph nodes, and we performed partial penectomy with bilateral superficial inguinal lymph node dissection in July 2016. Because of the positive surgical margin 2 cm away from the tumor we performed a total penectomy 2 weeks after the previous operation. Histopathological examination revealed no residual tumor and negative inguinal lymph nodes. In about 3 months postoperatively, he presented with a complaint of dyspnea and a CT scan showed right, pleural effusion and multiple lung metastases. He died of cancer 4 months postoperatively.

[Penile Metastasis from Invasive Bladder Carcinoma Diagnosed by Needle Biopsy : A Case Report and Literature Review].

A 62-year-old man presented to our hospital with the chief complaint of continuous penile pain and swelling for 4 months. Computed tomography and magnetic resonance imaging showed an invasive bladder tumor with penile, bone, and lymph node metastases. Needle biopsies of the bladder and penile lesions were obtained, and histological evaluation of these specimens revealed urothelial carcinoma, findings which are consistent with invasive bladder cancer with penile metastasis. After several therapeutic options were discussed with the patient, he decided toundergogeneral chemotherapy. However, the patient died about 16 days after admission without treatment because of his poor general condition.

[Application value of ultrasonography in penile diseases].

Penile disease is one of the male urological diseases. Although the penis is a small organ, once the problem occurs, it often brings great trouble to the patient. Therefore, the accurate diagnosis of penile disease is particularly important. High-frequency ultrasonography, with its advantages of noninvasiveness, safety, low cost, easy operation and reproducibility, can clearly show the structure and blood flow of the penis and has a significant value in the diagnosis and follow-up of penile diseases such as vascular erectile dysfunction, priapism, penile injury, penile neoplastic and non neoplastic nodules. Meanwhile, the development of new technologies such as shear wave elastography (SWE) and contrast enhanced ultrasound (CEUS) has made up for the shortcomings of traditional ultrasound imaging, expanded the application of ultrasound in penile diseases, and improved the efficiency of ultrasound diagnosis of the diseases. This article focuses on the application value of ultrasound in erectile dysfunction, priapism, penile cavernous injury and penile tubercle, as well as the latest progress in such new technologies as SWE and CEUS applied to penile diseases.

Investigating the role of SPECT/CT in dynamic sentinel lymph node biopsy for penile cancers.

PURPOSE: Currently, most centres use 2-D planar lymphoscintigraphy when performing dynamic sentinel lymph node biopsy in penile cancer patients with clinically impalpable inguinal nodes. This study aimed to investigate the role of SPECT/CT following 2-D planar lymphoscintigraphy (dynamic and static) in the detection and localization of sentinel lymph nodes in the groin. METHODS: A qualitative (visual) review was performed on planar followed by SPECT/CT lymphoscintigraphy in 115 consecutive patients (age 28-86 years) who underwent injection of 99mTc-nanocolloid followed by immediate acquisition of dynamic (20 min) and early static scans (5 min) initially and further delayed static (5 min) images at 120 min followed by SPECT/CT imaging. The lymph nodes detected in each groin on planar lymphoscintigraphy and SPECT/CT were compared. RESULTS: A total of 440 and 467 nodes were identified on planar scintigraphy and SPECT/CT, respectively. Overall, SPECT/CT confirmed the findings of planar imaging in 28/115 cases (24%). In the remaining 87 cases (76%), gross discrepancies were observed between planar and SPECT/CT images. SPECT/CT identified 17 instances of skin contamination (16 patients, 13%) and 36 instances of in-transit lymphatic tract activity (24 patients, 20%) that had been interpreted as tracer-avid lymph nodes on planar imaging. In addition, SPECT/CT identified 53 tracer-avid nodes in 48 patients (42%) that were not visualized on planar imaging and led to reclassification of the drainage basins (pelvic/inguinal) of 27 tracer-avid nodes. CONCLUSIONS: The addition of SPECT/CT improved the rate of detection of true tracer-avid lymph nodes and delineated their precise (3-D) anatomic localization in drainage basins.

Incremental value of MRI for preoperative penile cancer staging.

PURPOSE: To evaluate the incremental value of magnetic resonance imaging (MRI), compared to clinical examination, for penile cancer (PC) local staging. MATERIALS AND METHODS: Twenty-five consecutive patients with histologically proven PC were evaluated prospectively. MRI staging was performed on 1.5 and 3.0T scanners using high-resolution T2 -weighted and postcontrast T1 -weighted images. Two blinded observers interpreted MR images. Clinical local staging was performed by experienced urologists. The pathology report was used as the standard of reference. RESULTS: The interobserver agreement for MRI staging, using a kappa test for T-staging was moderate, 0.52 (95% confidence interval [CI] = 0.24-0.78), P = 0.001, although a high correlation for N-staging, 0.72 (95% CI = 0.42-1.00), P = 0.001, was detected. Clinical staging was correct in 52.0% (13/25) of patients. After pathological staging, five (20.0%) lesions were upstaged and seven (28.0%) lesions were downstaged compared to clinical examination. MRI accurately defined T-staging in 18/25 lesions (72.0%). After pathologic staging, five (20.0%) were upstaged and two downstaged (8.0%), compared to MRI. Fifteen patients were submitted to inguinal and pelvic lymphadenectomy and considered for comparison of accuracy of nodal staging by physical examination and MRI. Clinical staging accurately staged 7/15 patients (46.7%). After histopathologic analysis, six cases had nodal staging upgraded and two cases were downgraded. MRI correctly staged 13/15 (86.7%). Using a chi-square for comparison, differences in proportion of corrected staging between clinical examination and MRI were not significant for T-staging (P = 0.14), but were significant for nodal staging (P = 0.02). CONCLUSION: According to our results, MRI improves local staging of PC patients, particularly for those with limited physical examination. LEVEL OF EVIDENCE: 1 J. Magn. Reson. Imaging 2017;45:118-124.

Management of non-visualization following dynamic sentinel lymph node biopsy for squamous cell carcinoma of the penis.

OBJECTIVES: To review the management and clinical outcomes of uni- or bilateral non-visualization of inguinal lymph nodes during dynamic sentinel lymph node biopsy (DSNB) in patients diagnosed with penile cancer and clinically impalpable inguinal lymph nodes (cN0), and to develop an algorithm for the management of patients in which non-visualization occurs. PATIENTS AND METHODS: This is a retrospective observational study over a period of 4 years, comprising 166 patients with penile squamous cell carcinoma undergoing DSNB and followed up for a minimum of 6 months. All cases diagnosed with uni- or bilateral non-visualization of sentinel nodes in this cohort were identified from a penile cancer database. The management of the inguinal lymph nodes after non-visualization and the oncological outcomes including local and regional recurrence rates were documented. RESULTS: Out of 166 consecutive patients undergoing DSNB, 20 patients (12%) had unilateral non-visualization after injection of intradermal 99m Tc. Of these 20 patients, seven underwent repeat DSNB at a later date, with six having successful visualization. One patient had persistent non-visualization and proceeded to a superficial modified inguinal lymphadenectomy (SML). None of these patients experienced recurrence at follow-up. A further seven patients underwent modified SML with on-table frozen-section analysis of the lymph node packet; none of these patients were found to have micrometastatic disease in the inguinal lymph nodes, although one patient developed metastatic inguinal node disease at a later date. Six patients elected to undergo clinical surveillance and have remained disease-free. CONCLUSION: Patients with impalpable inguinal lymph nodes undergoing DSNB with ≥G2 T1 disease should ideally have bilateral visualization of the sentinel lymph nodes, reflecting the drainage pattern from the primary tumour. In the present series, 12% of patients were found to have unilateral non-visualization after DSNB. Among patients offered a repeat DSNB at a later date, localizing the sentinel node was successful in 86% of cases. Patients with favourable histological characteristics can be placed on clinical surveillance. Those with high-risk disease can be offered a repeat DSNB procedure on the proviso that SML may be carried out if there is repeated non-visualization. Larger cohorts are required to validate this proposed algorithm.

Advancements in staging and imaging for penile cancer.

PURPOSE OF REVIEW: We review recent advancements in staging and imaging of penile cancer, including surveillance after therapy. RECENT FINDINGS: For cN0 patients, the sentinel lymph node biopsy is currently considered the preferred way for invasive staging. It has largely replaced other modalities such as staging inguinal lymphadenectomy. Its diagnostic value increases when combined with other staging modalities such as ultrasound with fine-needle aspiration cytology (US-FNAC) or fluorodeoxyglucose-PET with computed tomography (PET/CT). In patients with palpably suspicious nodes (cN+), imaging is more useful. PET/CT has shown good accuracy in a limited number of small studies. US-FNAC can confirm nodal metastatic disease. A staging inguinal lymphadenectomy is of therapeutic value but is associated with significant morbidity. Omitting staging inguinal lymphadenectomy was recently described; one study showed well tolerated use of sentinel lymph node biopsy combined with intraoperative ultrasound-guided resection of suspicious nodes in cN+ patients. Therapeutic inguinal lymphadenectomy was only performed in the 42% of groins with metastases confirmed by disorder. For M-staging, PET/CT has shown good sensitivity, and its role should be further evaluated. Follow-up and surveillance rely on physical examination and US-FNAC. SUMMARY: Over the past decade, staging and treatment of penile cancer have become less invasive, while survival tends to improve.

(Near-Infrared) Fluorescence-Guided Surgery Under Ambient Light Conditions: A Next Step to Embedment of the Technology in Clinical Routine.

BACKGROUND AND PURPOSE: In open surgery procedures, after temporarily dimming the lights in the operation theatre, the Photo Dynamic Eye (PDE) fluorescence camera has, amongst others, been used for fluorescence-guided sentinel node (SN) biopsy procedures. To improve the clinical utility and logistics of fluorescence-guided surgery, we developed and evaluated a prototype modified PDE (m-PDE) fluorescence camera system. METHODS: The m-PDE works under ambient light conditions and includes a white light mode and a pseudo-green-colored fluorescence mode (including a gray-scaled anatomical background). Twenty-seven patients scheduled for SN biopsy for (head and neck) melanoma (n = 16), oral cavity (n = 6), or penile (n = 5) cancer were included. The number and location of SNs were determined following an indocyanine green-(99m)Tc-nanocolloid injection and preoperative imaging. Intraoperatively, fluorescence guidance was used to visualize the SNs. The m-PDE and conventional PDE were compared head-to-head in a phantom study, and in seven patients. In the remaining 20 patients, only the m-PDE was evaluated. RESULTS: Phantom study: The m-PDE was superior over the conventional PDE, with a detection sensitivity of 1.20 × 10(-11) M (vs. 3.08 × 10(-9) M) ICG in human serum albumin. In the head-to-head clinical comparison (n = 7), the m-PDE was also superior: (i) SN visualization: 100 versus 81.4 %; (ii) transcutaneous SN visualization: 40.7 versus 22.2 %; and (iii) lymphatic duct visualization: 7.4 versus 0 %. Findings were further underlined in the 20 additionally included patients. CONCLUSION: The m-PDE enhanced fluorescence imaging properties compared with its predecessor, and provides a next step towards routine integration of real-time fluorescence guidance in open surgery.

Value and efficiency of sentinel lymph node diagnostics in patients with penile carcinoma with palpable inguinal lymph nodes as a new multimodal, minimally invasive approach.

PURPOSE: The international guidelines recommend sentinel lymph node biopsy (SLNB) for lymph node staging in penile cancer with non-palpable inguinal lymph nodes (LN) but it is not recommended with palpable inguinal LN. The aim of this study was to evaluate the reliability and morbidity of SLNB in combination with an ultrasound-guided resection of suspect inguinal LNs as a new multimodal, minimally invasive staging approach in these patients. METHODS: We performed SLNB in 26 penile cancer patients with 42 palpable inguinal LNs. Prior to the combined staging procedures the patients underwent an ultrasound examination of the groins as well as planar lymphatic drainage scintigraphy and SPECT/CT scans. During the surgical procedure, the radioactive-labelled sentinel lymph nodes and, in addition, sonographically suspect LNs, were resected under ultrasound guidance. Follow-up screening was done by ultrasound examination of the groins according to the guidelines of the European Association of Urology. RESULTS: Nineteen groins of 42 preoperatively palpable inguinal findings were histologically tumor-positive. SLNB alone showed lymphogenic metastases in 14 groins. Sonography revealed five further metastatic groins, which would not have been detected during SLNB due to a tumor-related blockage of lymphatic drainage or a so-called re-routing of the tracer. During follow-up, none of the 28 groins with tumor-negative LN status showed any LN recurrence in this combined investigation technique. The median follow-up period was 46 (24 to 92) months. Morbidity of this procedure was low at 4.76 % in relation to the number of groins resp. 7.69 % in relation to the number of patients. CONCLUSIONS: The results show that this combined procedure is a reliable multimodal diagnostic approach for treatment of penile cancer patients with palpable inguinal LNs. It is associated with low morbidity rates. SLNB alone would lead to a significantly higher false-negative rate in these patients. The encouraging results of this work can extend the range of indications for nuclear medicine in the form of SLNB using radioactive tracers in this patient group.

DaPeCa-3: promising results of sentinel node biopsy combined with (18) F-fluorodeoxyglucose positron emission tomography/computed tomography in clinically lymph node-negative patients with penile cancer - a national study from Denmark.

OBJECTIVES: To estimate the diagnostic accuracy of sentinel node biopsy (SNB) combined with preoperative (18) F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) for inguinal lymph node (LN) evaluation in patients with invasive penile squamous cell carcinoma (PSCC) with no clinical evidence of inguinal metastases (cN0) at two tertiary centres with complete clinical follow-up. PATIENTS AND METHODS: From April 2010 in Centre one and from January 2013 in Centre two, we prospectively enrolled patients diagnosed with invasive PSCC and scheduled for SNB at the only two university centres treating penile cancer in Denmark. All patients had FDG PET/CT before SNB. The sentinel LNs were preoperatively located by planar lymphoscintigraphy in 134 groins (68 patients) and by single-photon emission CT/CT in 120 groins (61 patients). The primary endpoints were the sensitivity, specificity, and false-negative rate of SNB combined with FDG PET/CT. The secondary endpoint was SNB-related morbidity. RESULTS: We examined 254 groins in 129 patients by SNB combined with FDG PET/CT. The median (interquartile range, IQR) follow-up of survivors was 23 (14-35) months. Of 201 LN-negative groins, two were false negatives, and despite radio-chemotherapy treatment, both patients died from penile cancer. Four of 23 radiotracer-silent groins, had a FDG PET/CT-positive LNs and were surgically explored. In one of four of the explored groins, a positive LN was found. Combined FDG PET/CT-SNB sensitivity was 94.4% (95% confidence interval [CI] 81-99%) per groin. The false-negative rate was 5.6% (95% CI 1-19%) per groin. In 15 patients (11.6%) there were 25 SNB-related complications of Clavien-Dindo grades I-IIIa. The only Clavien-Dindo IIIa complication was an inguinal lymphocele treated by aspiration. CONCLUSION: In this study, we present a favourable SNB false-negative rate of 5.6% in a national cohort of clinically LN-negative patients with invasive PSCC with a pre-SNB FDG PET/CT scan. The combination of FDG PET/CT and SNB seems to be a promising diagnostic approach. Even so, a false-negative SNB was fatal in two of two cases and we are determined to continue the development of our SNB technique. The SNB-related morbidity was limited.