Investigation of the distribution of inguinal lymph nodes and delineation of the inguinal clinical target volume using 18F-FDG PET/CT.

OBJECTIVE: Radiotherapy is a crucial treatment modality for pelvic cancers, but uncertainties persist in defining the clinical target volume (CTV) for the inguinal lymphatic drainage region. Suboptimal CTV delineation may compromise treatment efficacy and result in subpar disease control. This study aimed to investigate and map the distribution of lymph node metastases (LNM) in the groin area to facilitate an improved and detailed CTV definition using 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT). METHODS: Inguinal LNM in patients with biopsy-proven pelvic malignancies were identified using 18F-FDG PET/CT scan. The longitudinally nearest axial plane was determined based on six typical bony landmarks, and the axial direction relative to the femoral artery of LNM was recorded. The distances from the LNM to the nearest edge of the femoral artery were measured on the axial plane. An optimal margin to cover 95% of LNM was estimated to develop contouring recommendations. RESULTS: In this study, 500 positive LNM were identified by 18F-FDG PET/CT among 185 patients with primary pelvic malignancies. Relative to the femoral artery, lymph nodes were distributed laterally (10:00-11:00, n = 35), anteriorly (12:00-1:00, n = 213), and medially (2:00-4: 00, n = 252). For CTV delineation, the recommended distances from the femoral artery on the SFH were lateral 19 mm, anterior 19 mm, and medial 25 mm; on the SGT were lateral 26 mm, anterior 20 mm, and medial 25 mm; on the SPS were lateral 28 mm, anterior 29 mm, and medial 26 mm; on the IPS were anterior 29 mm and medial 28 mm; on the IIT were anterior 27 mm and medial 27 mm; on the ILT were anterior 25 mm and medial 23 mm. Use interpolation to contour the area between six axial slices, including any radiographically suspicious LNM. CONCLUSIONS: Using 18F-FDG PET/CT, we investigated the distribution pattern of inguinal LNM and propose a more comprehensive guideline for inguinal CTV delineation.

Preoperative prediction model of lymph node metastasis in the inguinal and femoral region based on radiomics and artificial intelligence.

OBJECTIVE: To predict preoperative inguinal lymph node metastasis in vulvar cancer patients using a machine learning model based on imaging features and clinical data from pelvic magnetic resonance imaging (MRI). METHODS: 52 vulvar cancer patients were divided into a training set (n=37) and validation set (n=15). Clinical data and MRI images were collected, and regions of interest were delineated by experienced radiologists. A total of 1688 quantitative imaging features were extracted using the Radcloud platform. Dimensionality reduction and feature selection were applied, resulting in a radiomics signature. Clinical characteristics were screened, and a combined model integrating the radiomics signature and significant clinical features was constructed using logistic regression. Four machine learning classifiers (K nearest neighbor, random forest, adaptive boosting, and latent dirichlet allocation) were trained and validated. Model performance was evaluated using the receiver operating characteristic curve and the area under the curve (AUC), as well as decision curve analysis. RESULTS: The radiomics score significantly differentiated between lymph node metastasis positive and negative patients in both the training and validation sets. The combined model demonstrated excellent discrimination, with AUC values of 0.941 and 0.933 in the training and validation sets, respectively. The calibration curve and decision curve analysis confirmed the model's high predictive accuracy and clinical utility. Among the machine learning classifiers, latent dirichlet allocation and random forest models achieved AUC values >0.7 in the validation set. Integrating all four classifiers resulted in a total model with an AUC of 0.717 in the validation set. CONCLUSION: Radiomics combined with artificial intelligence can provide a new method for prediction of inguinal lymph node metastasis of vulvar cancer before surgery.

Reduced Fascicle Area Demonstrated in Ilioinguinal Nerves Resected from Primary Inguinal Herniorrhaphy Patients as Evidence of Compression Neuropathy.

Methods: 30 male patients with primary inguinal hernias undergoing primary inguinal herniorrhaphy were prospectively recruited for ilioinguinal nerve resection and evaluation. Three samples of the resected ilioinguinal nerve (proximal, canal, and distal) were evaluated using Masson's trichrome stain to measure fascicle and total nerve cross-sectional area and detect changes in collagen. Results: The fascicle cross-sectional area in the canal segment was significantly decreased compared to the proximal control with a large effect size observed (p = 0.016, η2 = 0.16). There was no significant difference in the nerve cross-sectional area between locations, but there was a moderate to large effect size observed between locations (p = 0.165, η2 = 0.105). There was no significant difference in collagen content nor effect size observed between locations (p = 0.99, η2 = 1.503 × 10-4). Interpretation. The decrease in the fascicle cross-sectional area within the inguinal canal further suggests that there is chronic pressure applied by hernia tissue consistent with axon degeneration. Collagen content is uniformly distributed along the length of the nerve. Further studies with larger samples are needed to confirm the observed effect of nerve location on the total nerve cross-sectional area and axon loss.

MRI Texture Analysis of Inguinal Lymph Node Metastasis in Vulvar Cancer - Associations With Histopathology.

BACKGROUND/AIM: Texture analysis is a quantitative imaging technique that provides novel biomarkers beyond conventional image reading. This study aimed to investigate the correlation between texture parameters and histopathological features of lymph nodes in patients with vulvar cancer. PATIENTS AND METHODS: Overall, nine female patients (mean age 70.1±13.4 years, range=39-87 years) were included in the analysis. All patients had squamous cell carcinomas and underwent upfront surgery with inguinal lymph node resection. Immunohistochemical assessment was performed using several markers of the epithelial-mesenchymal transition. The presurgical magnetic resonance imaging (MRI) was analyzed with the MaZda package. RESULTS: In discrimination analysis, several parameters derived from T1-weighted images showed statistically significant differences between non-metastatic and metastatic lymph nodes. The highest statistical significance was reached by the texture feature "S(0,3)InvDfMom" (p=0.016). In correlation analysis, significant associations were found between MRI texture parameters derived from both T1-weighted and T2-weighted images and the investigated histopathological features. Notably, S(0,3)InvDfMom derived from T1-weighted images highly correlated with the Vimentin-score (r=0.908, p=0.001). CONCLUSION: Several associations between MRI texture analysis and immunohistochemical parameters were identified in metastasized lymph nodes of cases with vulvar cancer.

Robot-Assisted Video Endoscopic Inguinal Lymph Node Dissection for Penile Cancer: An Indian Multicenter Experience.

Objective: To report outcomes of multicenter series of penile cancer patients undergoing robot-assisted video endoscopic inguinal lymph node dissection (RA-VEIL). Materials and Methods: In this retrospective analysis from 3 tertiary care centers in India, consecutive intermediate-/high-risk carcinoma penis (CaP) patients with nonpalpable inguinal lymphadenopathy and/or nonbulky (<3 cm) mobile inguinal lymphadenopathy undergoing RA-VEIL were included. Patients with matted/bulky (>3 cm) and fixed lymphadenopathy were excluded. Demographic, clinical, and intraoperative data were recorded. Perioperative complications were graded by the Clavien-Dindo classification (CDC). The International Society of Lymphology (ISL) {0-III} grading was used for the assessment of lymphedema. Incidence and pattern of recurrences were assessed on follow-up. Results: From January 1, 2011, to September 30, 2023, 115 patients (230 groins) underwent bilateral RA-VEIL for CaP. The median age of the cohort was 60 (50-69) years. Clinically palpable (either unilateral or bilateral) inguinal lymphadenopathy was seen in 54 patients (47%). The "per groin" median operative time was 120 (100-140) minutes with median lymph node yield of 12 (9-16). No complications were recorded in 87.8% groins operated, with major complications (CDC 3) seen in 2.6% groins. At a median follow-up of 13.5 months, 13 patients had documented recurrences and there were 10 cancer-related deaths. No port-site recurrences were observed. No/minimal lymphedema (ISL 0/I) was seen in 94% legs. Conclusion: RA-VEIL demonstrates safety and oncologic efficacy in penile cancer patients presenting with clinically nonpalpable and/or nonbulky inguinal lymphadenopathy, with favorable functional outcomes.

Leg Lymphoedema After Inguinal and Ilio-Inguinal Lymphadenectomy for Melanoma: Results from a Prospective, Randomised Trial.

BACKGROUND: The Evaluation of Groin Lymphadenectomy Extent for Melanoma (EAGLE FM) study sought to address the question of whether to perform inguinal (IL) or ilio-inguinal lymphadenectomy (I-IL) for patients with inguinal nodal metastatic melanoma who have no clinical or imaging evidence of pelvic disease. Primary outcome measure was disease-free survival at 5 years, and secondary endpoints included lymphoedema. METHODS: EAGLE FM was designed to recruit 634 patients but closed with 88 patients randomised because of slow recruitment and changes in melanoma management. Lymphoedema assessments occurred preoperatively and at 6, 12, 18, and 24 months postoperatively. Lymphoedema was defined as Inter-Limb Volume Difference (ILVD) > 10%, Lymphoedema Index (L-Dex®) > 10 or change of L-Dex® > 10 from baseline. RESULTS: Prevalence of leg lymphoedema between the two groups was similar but numerically higher for I-IL at all time points in the first 24 months of follow-up; highest at 6 months (45.9% IL [CI 29.9-62.0%], 54.1% I-IL [CI 38.0-70.1%]) and lowest at 18 months (18.8% IL [CI 5.2-32.3%], 41.4% I-IL [CI 23.5-59.3%]). Median ILVD at 24 months for those affected by lymphoedema was 14.5% (IQR 10.6-18.7%) and L-Dex® was 12.6 (IQR 9.0-17.2). There was not enough statistical evidence to support associations between lymphoedema and extent of surgery, radiotherapy, or wound infection. CONCLUSIONS: Despite a trend for patients who had I-IL to have greater lymphoedema prevalence than IL in the first 24 months after surgery, our study's small sample did not have the statistical evidence to support an overall difference between the surgical groups.

Inguinal endometriosis: a case series and review of the literature.

BACKGROUND: Inguinal endometriosis is one of the most common forms of endometriosis. The present study introduces 8 cases of inguinal endometriosis and discusses probable theories of inguinal endometriosis by reviewing the literature. CASE PRESENTATION: 8 Iranian cases of inguinal endometriosis with a mean age of 36 years were presented. Catamenial groin pain and swelling were the most common complications. Also, patients usually had accompanying symptoms such as pelvic pain and dysmenorrhea. One-half of patients had a history of previous abdominal surgery. Ultrasound was diagnostic in 4 patients (50%), and magnetic resonance imaging was used in two patients (25%). Among 6 patients who underwent hormonal therapy, 4 experienced an endometriosis size increase. Inguinal endometriosis was right-sided in 87.5% of patients, and among 4 patients who underwent surgery, 75% had proximal site involvement of the round ligament. CONCLUSION: According to the rarity of inguinal endometriosis, it is more likely to be a misdiagnosis with other inguinal disorders such as inguinal hernia. Inguinal endometriosis should be considered in patients who undergo inguinal herniorrhaphy, with suspected findings such as thickening of the hernia sac wall, bloody fluid inside the sac, or thickening of the extraperitoneal round ligament during the surgery.

Robotic or open superficial inguinal lymph node dissection as staging procedures for clinically node negative high risk penile cancer.

OBJECTIVE: To evaluate perioperative and oncologic outcomes of a cohort of clinically node negative high-risk penile cancer patients undergoing robotic assisted inguinal lymph node dissection (RAIL) compared to patients undergoing open superficial inguinal lymph node dissection (OSILND). PATIENTS AND METHODS: We retrospectively reviewed the clinical characteristics and outcomes of clinically node negative high-risk penile cancer patients undergoing RAIL at MDACC from 2013-2019. We sought to compare this to a contemporary open cohort of clinically node negative patients treated from 1999 to 2019 at MDACC and Moffit Cancer Center (MCC) with an OSILND. Descriptive statistics were used to characterize the study cohorts. Comparison analysis between operative variables was performed using Fisher's exact test and Wilcoxon's rank-sum test. The Kaplan-Meier method was used to estimate survival endpoints. RESULTS: There were 24 patients in the RAIL cohort, and 35 in the OSILND cohort. Among the surgical variables, operative time (348.5 minutes vs. 239.0 minutes, P < 0.01) and the duration of operative drain (37 vs. 22 days P = 0.017) were both significantly longer in the RAIL cohort. Complication incidences were similar for both cohorts (34.3% for OSILND vs. 33.3% for RAIL), with wound complications making up 33% of all complications for RAIL and 31% of complications for OSILND. No inguinal recurrences were noted in either cohort. The median follow-up was 40 months for RAIL and 33 months for OSILND. CONCLUSIONS: We observed similar complication rates and surgical variable outcomes in our analysis apart from operative time and operative drain duration. Oncological outcomes were similar between the two cohorts. RAIL was a reliable staging and potentially therapeutic procedure among clinically node negative patients with penile squamous cell carcinoma with comparable outcomes to an OSILND cohort.

Regional lymph node mapping in patients with penile cancer undergoing radical inguinal lymph node dissection - a retrospective cohort study.

BACKGROUND: Radical inguinal lymph node dissection (rILND) is the most available treatment to cure penile cancer (PC) with limited inguinal-confined disease. However, guidelines regarding acceptable boundaries of rILND are controversial, and consensus is lacking. The authors aimed to standardize the surgical boundaries of rILND with definite pathological evidence and explore the distribution pattern of inguinal lymph nodes (ILNs) in PC. METHODS: A total of 414 PC patients from two centers who underwent rILND were enrolled. The ILN distribution was divided into seven zones anatomically for pathological examination. Student's t test and Kaplan-Meier survival analysis were used. RESULTS: ILNs displayed a funnel-shaped distribution with high density in superior regions. ILNs and metastatic nodes are present anywhere within the radical boundaries. Positive ILNs were mainly concentrated in zone I (51.7%) and zone II (41.3%), but there were 8.7% and 12.3% in inferior zones V and VI, respectively, and 7.1% in the deep ILNs. More importantly, a single positive ILN and first-station positive zone was detected in all seven regions. Single positive ILNs were located in zones I through VI in 40.4%, 23.6%, 6.7%, 18.0%, 4.5%, and 1.1%, respectively, and 5.6% presented deep ILN metastasis directly. CONCLUSIONS: The authors established a detailed ILN distribution map and displayed lymphatic drainage patterns with definite pathological evidence using a large cohort of PC patients. Single positive ILNs and first-station metastatic zones were observed in any region, even directly with deep ILN metastasis. Only rILND can ensure tumor-free resection without the omission of positive nodes.

Comparison of Early Inguinal Lymph Node Dissection and Neoadjuvant Chemotherapy in Penile Cancer Patient with Bulky Nodal Metastasis: A Cohort Study.

PURPOSE: Penile cancer is a rare malignancy, where extranodal extension in inguinal or pelvic lymph nodes is associated with decreased 5-year cancer-survival rate in this study, we try to assess survival and quality of life in a penile cancer patient with bulky lymph node. METHODS: We retrospectively reviewed data from penile cancer patients with bulky lymph nodes who underwent treatment between July 2016 and July 2021 at tertiary referral hospital care. The inclusion criteria (age >18 yr, histologically proven penile cancer, and completion of last treatment 6 months prior to this study) yielded a cohort of 20 eligible penile cancer patients with bulky lymph nodes (> 4 cm/bilateral mobile/unilateral fixed). Only patients who had completed therapy at least 6 months prior to the study were included. After obtaining consent, they were asked to complete the EORTC QLQ-C30 questionnaire to evaluate the patient's quality of life. RESULTS: Out of 20 patients, 5 patients underwent direct ILND and 15 patients underwent chemotherapy. Median follow-up after primary diagnosis was 114+32 months in patients with early ILND and 52+11 months in patients who underwent delayed lymph node dissection. Out of 5 patients who underwent early ILND, all of them survived during follow-up, and achieved cancer-free status without residual tumor and with excellent functional outcomes (Karnofsky 90). There was no significant difference in social function (p-value = 0.551), physical function (p-value = 0.272), role function (p-value = 0.546), emotional function (p-value = 0.551), cognitive function (p-value = 0.453), and global health status (p-value = 0.893) between patient which treated with early ILND and Neoadjuvant Chemotherapy. However, patients who underwent early ILND showed a relatively better clinical outcome. CONCLUSION: Early ILND followed by adjuvant chemotherapy for penile cancer with palpable lymph nodes is more favourable than neoadjuvant TIP chemotherapy.

Surgical templates for inguinal lymph node dissection in cN0 penile cancer: A comparative study.

PURPOSE: Modified and superficial inguinal lymph node dissection (MILD and SILD) are the 2 widely used templates for surgical staging of clinically node negative (cN0) penile cancer (PeCa); however, no previous reports have compared their outcomes. We compared these 2 surgical templates for oncological outcomes and complications. MATERIALS AND METHODS: We retrospectively reviewed records of cN0 PeCa patients who underwent MILD/SILD at our cancer care center from January 2013 to December 2019. Patients who developed a penile recurrence during follow up were excluded from analysis of oncological outcomes. The 2 groups (MILD and SILD) were compared for baseline clinico-pathological characteristics. The primary outcome was the groin recurrence free survival (gRFS). Secondary outcomes included the false negative rate (FNR) and disease free survival (DFS) for both templates and also the post-operative wound related complication. RESULTS: Of the 146 patients with intermediate and high risk N0 PeCa, 74 (50.7%) and 72 (49.3%) underwent MILD and SILD respectively. The 2 groups were comparable with regards to the distribution of T stage, tumor grade and the proportion of intermediate and high-risk patients. At a median follow up of 34 months (47 for SILD and 23 for MILD), a total of 5 groin recurrences were encountered; all of them occurred in the MILD group. The gRFS and DFS for the MILD group was 93.2% and 91.8% respectively; while that for the SILD group was 100% and 94.4% respectively. Too few events had occurred to determine any statistically significant difference. The FNR for MILD and SILD was 26.3% and 0% respectively. The overall complication rate was significantly higher in the SILD group (46% vs 20.3%, p=0.001), especially for Clavien Dindo 3A complications. CONCLUSION: MILD can fail to pick up micro-metastatic disease in a small proportion of cN0 PeCa patients, while SILD provides better oncological clearance with no groin recurrences. This oncological superiority comes at the cost of a higher incidence of wound-related complications.

Long-term oncological and surgical outcomes after Video Endoscopic Inguinal Lymphadenectomy (VEIL) in patients with penile cancer.

OBJECTIVE: To report outcomes from the largest multicenter series of penile cancer patients undergoing video endoscopic inguinal lymphadenectomy (VEIL). MATERIALS AND METHODS: Retrospective multicenter analysis. Authors of 21 centers from the Penile Cancer Collaborative Coalition-Latin America (PeC-LA) were included. All centers performed the procedure following the same previously described standardized technique. Inclusion criteria included penile cancer patients with no palpable lymph nodes and intermediate/high-risk disease and those with non-fixed palpable lymph nodes less than 4 cm in diameter. Categorical variables are shown as percentages and frequencies whereas continuous variables as mean and range. RESULTS: From 2006 to 2020, 210 VEIL procedures were performed in 105 patients. Mean age was 58 (45-68) years old. Mean operative time was 90 minutes (60-120). Mean lymph node yield was 10 nodes (6-16). Complication rate was 15.7%, including severe complications in 1.9% of procedures. Lymphatic and skin complications were noted in 8.6 and 4.8% of patients, respectively. Histopathological analysis revealed lymph node involvement in 26.7% of patients with non-palpable nodes. Inguinal recurrence was observed in 2.8% of patients. 10y- overall survival was 74.2% and 10-y cancer specific survival was 84.8%. CSS for pN0, pN1, pN2 and pN3 were 100%, 82.4%, 72.7% and 9.1%, respectively. CONCLUSION: VEIL seems to offer appropriate long term oncological control with minimal morbidity. In the absence of non-invasive stratification measures such as dynamic sentinel node biopsy, VEIL emerged as the alternative for the management of non-bulky lymph nodes in penile cancer.

Primary spontaneous inguinal endometriosis: Two cases with emphasis on the diagnostic approach.

OBJECTIVE: While endometriosis is common, inguinal endometriosis with hernia is rarely observed, making its preoperative diagnosis challenging. CASE REPORT: We report two cases of inguinal endometriosis with different presentations and focus on tailored surgical treatment. The two patients in our series presented with painful swelling in the right groin area. Surgery and pathological examination confirmed the diagnosis of endometriosis in both cases. Herniorrhaphy and excision of the extraperitoneal round ligament were performed in one patient with concomitant inguinal endometriosis and indirect inguinal hernia. CONCLUSION: We highlight the importance of the preoperative evaluation of concomitant pelvic endometriosis, round ligament involvement, and endometriosis within the inguinal hernia sac. Inguinal endometriosis with or without hernia should be considered even in reproductive-aged women without a previous medical and surgical history. Postoperative hormonal therapy, including dienogest, can be considered to prevent disease recurrence.

Inguinal lymph node metastases from rectal adenocarcinoma: a systematic review.

PURPOSE: Inguinal lymph nodes are a rare but recognised site of metastasis in rectal adenocarcinoma. No guideline or consensus exists for the management of such cases. This review aims to provide a contemporary and comprehensive analysis of the published literature to aid clinical decision-making. METHODS: Systematic searches were performed using the PubMed, Embase, MEDLINE and Scopus and Cochrane CENTRAL Library databases from inception till December 2022. All studies reporting on the presentation, prognosis or management of patients with inguinal lymph node metastases (ILNM) were included. Pooled proportion meta-analyses were completed when possible and descriptive synthesis was utilised for the remaining outcomes. The Joanna Briggs Institute tool for case series was used to assess the risk of bias. RESULTS: Nineteen studies were eligible for inclusion, encompassing 18 case series and one population-based study using national registry data. A total of 487 patients were included in the primary studies. The prevalence of ILNM in rectal cancer is 0.36%. ILNM are associated with very low rectal tumours with a mean distance from the anal verge of 1.1 cm (95% CI 0.92-1.27). Invasion of the dentate line was found in 76% of cases (95% CI 59-93). In patients with isolated inguinal lymph node metastases, modern chemoradiotherapy regimens in combination with surgical excision of inguinal nodes are associated with 5-year overall survival rates of 53-78%. CONCLUSION: In specific subsets of patients with ILNM, curative-intent treatment regimens are feasible, with oncological outcomes akin to those demonstrated in locally advanced rectal cancers.

Reply to May et al. The Goal of Achieving High-Quality Surgical First-Line Therapy in Patients with Penile Cancer Is Important; However, Some Collective Efforts Are Still Required in Order to Reach It. Comment on "Brassetti et al. Combined Reporting of Surgical Quality and Cancer Control after Surgical Treatment for Penile Tumors with Inguinal Lymph Node Dissection: The Tetrafecta Achievement. Curr. Oncol. 2023, 30, 1882-1892".

We have carefully read the comment by May et al. [...].