Inguinal Nodes Research Articles

Murine alveolar macrophages rapidly accumulate intranasally administered SARS-CoV-2 Spike protein leading to neutrophil recruitment and damage.

The trimeric SARS-CoV-2 Spike protein mediates viral attachment facilitating cell entry. Most COVID-19 vaccines direct mammalian cells to express the Spike protein or deliver it directly via inoculation to engender a protective immune response. The trafficking and cellular tropism of the Spike protein in vivo and its impact on immune cells remains incompletely elucidated. In this study, we inoculated mice intranasally, intravenously, and subcutaneously with fluorescently labeled recombinant SARS-CoV-2 Spike protein. Using flow cytometry and imaging techniques, we analyzed its localization, immune cell tropism, and acute functional impact. Intranasal administration led to rapid lung alveolar macrophage uptake, pulmonary vascular leakage, and neutrophil recruitment and damage. When injected near the inguinal lymph node medullary, but not subcapsular macrophages, captured the protein, while scrotal injection recruited and fragmented neutrophils. Widespread endothelial and liver Kupffer cell uptake followed intravenous administration. Human peripheral blood cells B cells, neutrophils, monocytes, and myeloid dendritic cells all efficiently bound Spike protein. Exposure to the Spike protein enhanced neutrophil NETosis and augmented human macrophage TNF-α (tumor necrosis factor-α) and IL-6 production. Human and murine immune cells employed C-type lectin receptors and Siglecs to help capture the Spike protein. This study highlights the potential toxicity of the SARS-CoV-2 Spike protein for mammalian cells and illustrates the central role for alveolar macrophage in pathogenic protein uptake.

The challenges in diagnosing isolated epididymal tuberculosis (TB) in an adolescent male: a case report

BackgroundGenitourinary tuberculosis (GUTB) is a common form of extrapulmonary TB (EPTB) in children. An example of GUTB is epididymal TB, which usually presents unspecific chronic clinical manifestations. Definitive diagnosis can be conducted based on bacteriologic confirmation and histopathologic results, but this is challenging due to the paucibacillary nature of EPTB. Therefore, we reported the challenges in diagnosing isolated epididymal TB in an adolescent male.Case presentationA 16-year-old male presented to respirology clinic with painful swelling of the left scrotum for 3 months before visiting to the hospital. The symptoms were associated with persistent coughing for 2 months, and physical examination of the left scrotum showed swelling accompanied by cardinal signs. A palpable hard mass was found on the left scrotum, with firm borders, measuring 7 × 4 cm. Laboratory examination and tumor markers were within normal limits, although leukocyturia was found, and the urine culture was negative. Genital ultrasound (US) showed epididymitis sinistra with septal hydrocele, while magnetic resonance imaging (MRI) indicated inhomogeneous left epididymitis with bilateral inguinal lymph node enlargement. Although TB evaluation presented a negative purified protein derivative (PPD) test and bacteriologic examination, chest X-ray (CXR) showed perihilar lymphadenopathy. Based on the clinical and radiologic results suggesting TB, the patient was diagnosed with isolated epididymal TB and received quadruple antituberculosis therapy (ATT) for 6 months. After treatment, the left testicle size started to shrink and was equal to the right testicle, also, there were no signs of inflammation, the body weight increased by 5 kg, and cough disappeared. Sperm analysis at the end of treatment indicated teratozoospermia, which was subsequently treated by the urologic surgery department.ConclusionsBiopsy and bacteriologic confirmation for TB epididymitis were challenging to perform in the clinical setting. Epididymal TB should be considered in adolescent males with complaints of chronic scrotal swelling and pain. Clinical judgment based on history taking, physical examination, and radiologic features supporting TB features could be helpful in accurate and fast diagnosis for favorable outcome.

IgG4-related disease presenting as a pancreatic mass: A case report

Immunoglobulin G4-related disease (IgG4-RD) is an increasingly recognized fibroinflammatory condition with characteristic clinical, serological, and histopathological features. It might involve any organ in the body with a special predilection for lymph nodes, salivary glands, the pancreas, and the retroperitoneum. Due to the non-specific features of the disease and the capability of mimicking many other medical conditions, the diagnosis of IgG4-RD could be delayed. Herin, we describe a case of a middle-aged man who presented with obstructive jaundice due to a pancreatic mass. Further evaluation revealed multiple cervical and inguinal lymphadenopathy, bilateral wedge-shaped lesions in the kidneys and substantial thickening of the aortic wall that was suggestive of aortitis/periaortitis. A histopathological examination of an inguinal lymph node showed increased infiltration of nodal immunoglobulin G4 (IgG4) plasma cells (>30/high-power field) with a high serum IgG4 immunoglobulin level. Based on that, the patient was diagnosed with IgG4-RD, and he was successfully treated with pulse steroid therapy with complete resolution of his symptoms and the radiological and laboratory findings. IgG4-RD is a protean condition with a large spectrum of clinical manifestations that could mimic many other serious medical conditions. Early recognition and management of immunosuppression are vital for complete recovery.

The sonographic features of lymph node venous networks and flow patterns in patients with primary chronic venous disease.

Our study aims to enhance the understanding of lymph node venous networks (LNVNs) by summarising their anatomical, sonographic features, and reflux patterns. We examined 241 legs from 141 patients with primary chronic venous disease (CVD) using duplex ultrasound. The findings indicated variations in the shape, size, vascularity, and echogenicity of LNVN. The superficial inguinal lymph node with reflux appeared slightly larger, exhibiting higher velocities in the hilar artery. Regarding connections, venous flow within LNVN was predominantly drained through the saphenofemoral junction (SFJ), anterior accessory great saphenous vein (AAGSV), and great saphenous vein (GSV). A significant number of LNVNs were observed to be associated with anterolateral thigh tributaries. The study also identified valve cusps within LNVN. This study revealed a 12% prevalence of primary LNVN. Understanding the anatomical and haemodynamic features of LNVN informs treatment strategies and potentially helps prevent the recurrence of varicose veins.

Characteristics of Radiotherapy Treatment on Penile Squamous Cell Carsinoma

Background: Squamous cell carcinoma (SCC) of penis is rare cancer that originates from epithelial cells in the inner prepuce or glans of the penis. This study aims to investigate how the picture of radiotherapy treatment in penile squamous cell carcinoma at Arifin Achmad Hospital from 2014 to 2019. Materials and methods: This is a descriptive study using secondary data from medical records and radiotherapy for squamous carcinoma patients at Arifin Achmad Hospital, Riau Province from 2014 to 2019. Results: The results showed that there were 28 penile squamous cell carcinoma patients where 3 of them were treated with radiotherapy at Arifin Achmad Hospital, Riau Province from 2014 to 2019. The picture of radiotherapy management of penile squamous carcinoma based on the largest age group was the age range of 45-60 years old (100%) with the largest tribe being Batak (66.6%), with enlarged inguinal lymph nodes (100%). Mostly, they were in stage 4 (100%) with total penectomy operative management (100%). Most clinical symptoms that occurred were pain, sores, and itching around the genitals. Conclusion: Most cases of penile squamous cell carcinoma treated with radiotherapy. The patients were in the age range of 45-60 years old where most of them were from the Batak tribe, with enlarged inguinal lymph nodes. The investigations showed there were abnormalities and the patients experiencing stage 4. They were treated operatively with total penectomy. The clinical symptoms were a pain in the public area, sores around the genitals, and itching. The patients had dysuria complications as well.

Assessment of lymph node area coverage with total marrow irradiation and implementation of total marrow and lymphoid irradiation using automated deep learning-based segmentation.

Total marrow irradiation (TMI) and total marrow and lymphoid irradiation (TMLI) have the advantages. However, delineating target lesions according to TMI and TMLI plans is labor-intensive and time-consuming. In addition, although the delineation of target lesions between TMI and TMLI differs, the clinical distinction is not clear, and the lymph node (LN) area coverage during TMI remains uncertain. Accordingly, this study calculates the LN area coverage according to the TMI plan. Further, a deep learning-based model for delineating LN areas is trained and evaluated. Whole-body regional LN areas were manually contoured in patients treated according to a TMI plan. The dose coverage of the delineated LN areas in the TMI plan was estimated. To train the deep learning model for automatic segmentation, additional whole-body computed tomography data were obtained from other patients. The patients and data were divided into training/validation and test groups and models were developed using the "nnU-NET" framework. The trained models were evaluated using Dice similarity coefficient (DSC), precision, recall, and Hausdorff distance 95 (HD95). The time required to contour and trim predicted results manually using the deep learning model was measured and compared. The dose coverage for LN areas by TMI plan had V100% (the percentage of volume receiving 100% of the prescribed dose), V95%, and V90% median values of 46.0%, 62.1%, and 73.5%, respectively. The lowest V100% values were identified in the inguinal (14.7%), external iliac (21.8%), and para-aortic (42.8%) LNs. The median values of DSC, precision, recall, and HD95 of the trained model were 0.79, 0.83, 0.76, and 2.63, respectively. The time for manual contouring and simply modified predicted contouring were statistically significantly different. The dose coverage in the inguinal, external iliac, and para-aortic LN areas was suboptimal when treatment is administered according to the TMI plan. This research demonstrates that the automatic delineation of LN areas using deep learning can facilitate the implementation of TMLI.

Retrograde transvenous thoracic duct embolization for lymphatic leakage after retroperitoneal tumor and lymph node resection: a case report and literature review

BackgroundPostoperative lymphatic leakage is a complication of ineffective conservative treatment for retroperitoneal mass. Herein, we report a case of lymphatic leakage that arose after retroperitoneal tumor resection and that was treated with retrograde transvenous thoracic duct embolization.Case presentationA 28-year-old man with persistent abdominal pain was diagnosed with a large retroperitoneal metastatic tumor measuring 10 cm and a subdiaphragmatic lymph node originating from a testicular tumor. After high orchidectomy and neoadjuvant chemotherapy, the subdiaphragmatic lymph node and retroperitoneal tumor were resected together with the abdominal aorta; the latter was reconstructed using a prosthetic graft. Postoperatively, the patient developed chylothorax. No improvement was observed after conservative treatment that included fasting and somatostatin therapy. The leakage site could not be identified using antegrade lymphangiography of the bilateral inguinal lymph nodes, but was detected using retrograde transvenous lymphangiography. The leakage site was successfully embolized.ConclusionThis case report describes successful treatment with retrograde transvenous thoracic duct embolization for chylothorax following resection of a retroperitoneal tumor and lymph node. This approach is a less invasive and more effective mode of treatment for chylothorax and should be considered before surgical thoracic duct ligation when the leakage point cannot be identified using the antegrade approach.

(133) Non-Occupational SCC of the Scrotum; Case Presentation and Management

Abstract Introduction Although the incidence of scrotal malignancies is extremely low Squamous cell carcinoma (SCC) is the most common scrotal malignancy. Its overall annual incidence is approximately 1.5 per 1,000,000 persons in Western countries. It was first linked to the chronic irritation of scrotal skin by the effect of soot in occurring in chimney sweepers hence known as the first described occupational disease. Occupational scrotal SCC was also later described in association with other occupations with chronic carcinogen exposure including cotton mule spinners, paraffin and tar workers, creosote workers, shale oil workers, lathe workers, pitch workers and machine tool setters and operators. Currently most cases result from poor hygiene and chronic inflammation Objective Herein we present a very rare case of SCC of the scrotum referred to us from Dermatology department Methods This 55 years old male patient was referred from dermatology department. He had no underlying occupational hazard. He has been treated for several months of itchy inflammation of the scrotumfor 6 months. Scrotal punch biosy showed moderately differentiated SCC. Clinically there was malignant scrotal ulcer of 4x3 cm with no palpable inguinal lymph nodes. CT staging confirmed localized tumor with no LN or metastatic deposits. Complete excision with 2 cm safety margin confirmed to be negative by frozen section. Final histopathology come to be moderately differentiated SCC pT2Nx. All margins and underlying Dartos were free of tumor infiltration. Results Complete excision could be achieved with intra-operative negative frozen section. Uneventful post-operative course with complete healing of scrotal wound. Conclusions Although rare, scrotal SCC continues to be serious urogenital malignancy which should be suspected even in the absence of occupational exposure. Cooperation and awareness of Dermatologists is important for early detection and management of such rare malignancy. Complete excision with safety margin is usually sufficient for cure. Inguinal Lymphadenectomy is indicated if grossly infiltrated Disclosure No.

Formulation and In-vivo Characterization of 177Lu-tin-colloid as a Radiosynovectomy Agent.

Arthritis is an inflammatory disorder that affects one or more joints of the body for various reasons, including autoimmune disorders, trauma, or infection. In many cases, traditional long-term treatment with various drug combinations (NSAIDs, diseasemodifying antirheumatic drugs, systemic corticosteroids, etc.) can provide relief, but many joints require additional local treatment. Radiosynovectomy (RSV) is an alternative method to current treatment options. Both the global supply shortage of 90Y in recent years and the increasing use of 177Lu-labeled radiopharmaceuticals in the field of nuclear medicine have made it possible to develop 177Lu-labeled microparticles and test them in small groups as RSV agents. This study aimed to develop the 177Lu labeled tin colloid formulation and demonstrate its invivo characterization. Particle size, shape, and labelling efficiency of the four formulations developed were determined. The formula with the highest labelling efficiency was selected for further studies. The quality of the formulation was evaluated based on radionuclidic, radiochemical, and microbial purity. In-vitro stability was evaluated by determining the labelling efficiency. In-vitro stability was tested in PBS and synovial fluid. The biological characterization was assessed using SPECT/CT after injecting the formulation into the normal knee joints of the rabbits. Aggregated colloidal particles were spherical with a particle size of <5 μm. Labelling efficiency and radiochemical purity were >95 and 97.65% (Rf=0.2), respectively. The formulation was stable in vitro for up to 72 hours, both in PBS and synovial fluid. The formulation was homogeneously distributed in the joint at 0 and 1 hour after injection, and radioactivity- related involvement and inguinal lymph node involvement due to possible leakage were not detected in the late period. No pyrogenic/allergic side effects were observed during this period. 177Lu-tin-colloid was successfully prepared under optimized reaction conditions with high binding efficiency and radiochemical purity. The radiolabeled colloid was found to be stable in-vitro both in PBS and synovial fluid at room temperature. Serial PCET/CT images revealed that the activity was completely retained within the synovial cavity, with no activity leakage out of the joint until 48 hours after the injection. With the support of the results from further clinical studies, it may be possible for the formulation to enter clinical use.

T-cell non-Hodgkin lymphoma of lymphoblastic type revealed by a chronic swollen testicle managed in the urology department of Laquintinie Hospital in Douala, Cameroon

Background: Non-Hodgkin T-cell lymphomas typically develop in lymph node territories, and primary extra nodal locations are rare. The clinical presentation is nonspecific, dominated by signs of compression. Imaging aids in suspicion, and histology confirms the diagnosis. Clinical Observation: A 61-year-old patient initially hospitalized for the management of upper gastrointestinal bleeding six months ago was referred to the urology outpatient clinic due to a chronic swollen testicle persisting for a year. A non-contributory testicular ultrasound showed peri scrotal lymphedema with inguinal lymphadenopathy, right orchid epididymitis, and left epididymitis. Blood tests were normal. Despite antibiotic therapy, there was no improvement in the clinical condition. Physical examination revealed painless and mobile cervical, axillary, and inguinal lymph nodes. Pelvic MRI suspected a probable lymphoma. A lymph node biopsy in the left groin confirmed a non-Hodgkin T-cell lymphoma of lymphoblastic type infiltrating the capsule. The patient was transferred to haematology for further management. Conclusion: T-cell lymphoblastic lymphoma is primarily characterized by nodal involvement. There is a diagnostic delay that is anatomopathological in nature. Management involves polychemotherapy.

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

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. 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. 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. Early ILND followed by adjuvant chemotherapy for penile cancer with palpable lymph nodes is more favourable than neoadjuvant TIP chemotherapy.

Preoperative Albumin-to-Alkaline Phosphatase Ratio as an Independent Predictor of Lymph Node Involvement in Penile Cancer.

Background and Objectives: To investigate the role of preoperative albumin-to-alkaline phosphatase ratio (AAPR) in predicting pathologic node-positive (pN+) disease in penile cancer (PC) patients undergoing inguinal lymph node dissection (ILND). Materials and Methods: Clinical data of patients with squamous cell carcinoma (SCC) PC + ILND at a single high-volume institution between 2016 and 2021 were collected and retrospectively analyzed. An AAPR was obtained from preoperative blood analyses performed within 30 days from their scheduled surgery. A ROC curve analysis was used to assess AAPR cutoff, in addition to the Youden Index. Logistic regression analysis was utilized for an odds ratio (OR), 95% confidence interval (CI) calculations, and an estimate of pN+ disease. A p value < 0.05 was considered to be as statistically significant. Results: Overall, 42 PC patients were included in the study, with a mean age of 63.6 ± 12.9 years. The AAPR cut-off point value was determined to be 0.53. The ROC curve analysis reported an AUC of 0.698. On multivariable logistic regression analysis lymphovascular invasion (OR = 5.38; 95% CI: 1.47-9.93, p = 0.022), clinical node-positive disease (OR = 13.68; 95% CI: 4.37-43.90, p < 0.009), and albumin-to-alkaline phosphatase ratio ≤ 0.53 (OR = 3.61; 95% CI: 1.23-12.71, p = 0.032) were predictors of pN+ involvement. Conclusions: Preoperative AAPR may be a potentially valuable prognostic marker of pN+ disease in patients who underwent surgery for PC.

Le myofibroblastome palissadique intraganglionnaire : une cause rare d’adénopathie inguinale

IntroductionLymphadenopathies are a major cause of consultation in internal medicine, with various causes of diagnosis. Unexplained persistent lymphadenopathy must be biopsied to rule out malignant tumor. Case reportWe report the case of a 53-year-old man, with inguinal lymphadenopathy evolving for more than one year. The patient had no associated symptoms and his blood tests were unremarkable. Due to the progression of the adenopathy and its hypermetabolism on PET-CT, an excisional biopsy was performed. Histological analysis revealed an intranodal proliferation of spindle cells with a palisading pattern. β-catenine and smooth muscle actin labelling were positive, leading to the diagnosis of intranodal palisaded myofibroblastoma, a benign tumour. ConclusionIntranodal palisaded myofibroblastoma is a rare benign cause of adenopathy, with often inguinal lymph node localization and slow growth and without risk of recurrence after surgical removal.

Splenectomy at early stage of autoimmune arthritis delayed inflammatory response and reduced joint deterioration in mice.

The spleen plays a role in innate and adaptive immunity, and autoimmune diseases like rheumatoid arthritis (RA). We investigated the effect of splenectomy in early and moderate stages of autoimmune arthritis in a mouse model. To induce recombinant human G1-induced arthritis (GIA), BALB/c mice were immunized intraperitoneally three times in 4-week intervals with the rhG1 antigen. Mice were splenectomized on day 7 (SPE1) or day 35 (SPE2) after the initiation of immunization; tested for clinical severity, joint radiological and histological changes, serum levels of inflammatory cytokines and autoantibodies, and rhG1-specific immune responses; and compared to those in control mice with spleen left intact. Circulating Tregs and T-helper subset ratios in the spleen and inguinal lymph nodes (LNs) were also examined using flow cytometry. The onset of severe inflammatory response was significantly delayed in SPE1 and SPE2 groups compared to control mice at early stages of GIA, which was associated with increased circulating Tregs. After the third immunization, as disease progressed, the severity scores were robustly increased in all mice. Nevertheless, in splenectomized mice, we observed reduced joint deterioration and cartilage damage, more Th2 cells in LNs, and reduced levels of pro-inflammatory cytokines and autoantibodies in their sera. Mesenteric LN cells of splenectomized mice exhibited weaker response in vitro against the rhG1 antigen compared to control mice spleen. In conclusion, splenectomy in the early stages of GIA delayed the inflammatory response, suggesting a protective effect against the development and progression of severe destructive arthritis.

A comparative study of indocyanine green instillation in inguinal node versus foot web space using da Vinci indocyanine green FireFly™ technology in identifying thoracic duct during robotic-assisted transthoracic oesophagectomy.

Chyle leak is a serious complication following oesophagectomy with incidence varies from 1% to 9%. Near infra-red fluorescence imaging of thoracic duct (TD) can provide real-time dynamic imaging during the surgery. In this study, we intend to compare indocyanine green (ICG) dye instillation through inguinal node with subcutaneous first web space instillation for visualisation of TD during robotic-assisted minimally invasive oesophagectomy (RAMIE) procedure. A prospective study of 50 patients underwent RAMIE with da Vinci X System. After general anaesthesia, patients were divided into inguinal node and foot first web space ICG instillation group. The former group had 1 ml of ICG dye instilled on bilateral inguinal nodes under ultrasound guidance and while the other group received 1 mL of ICG dye injected at bilateral foot first web space and then underwent surgery. TD was visualised using ICG FireFly™ fluorescence technology, first at the time of docking and subsequently for every 5 min until 60 min of instillation time and analysed. Twenty-five patients were enrolled in each group. The mean docking time for thoracic phase was 13.76 ± 3.43 min. TD was visualised in 72% (18/25) of cases of first web space instillation group, whereas 100% in ultrasound guidance inguinal node instillation group. None of the patients had a chyle leak. ICG FireFly™ fluorescence technology for the identification of TD during oesophageal mobilisation is safe and effective and provides real-time dynamic visualisation with high accuracy in ultrasound-guided bilateral inguinal node instillation group. It is an effective method for the surgeons planning to negotiate their initial learning curve in RAMIE procedures.

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

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. 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. 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. 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.

Primary preputial reconstruction following surgical excision of cutaneous mast cell tumours without penile amputation in eight dogs

ABSTRACT Case history: Medical records from a single referral hospital (Davies Veterinary Specialists, Hitchin, UK) were reviewed to identify dogs (n = 8) with preputial cutaneous mast cell tumours (CMCT) that underwent surgical excision and primary preputial reconstruction, preserving the penis and urethra, after clients declined alternatives such as penile amputation and urethrostomy, from June 2017–June 2022. Clinical findings: Tumours had a median diameter of 21.5 (min 15, max 30) mm, were located cranioventrally (3/8), caudoventrally (1/8), laterally (2/8) and dorsally (2/8) relative to the prepuce and were diagnosed as CMCT based on cytology. No dogs had hepatic or splenic metastasis on cytology but inguinal lymph node metastasis was identified in 3/4 dogs sampled. Treatment and outcome: The owners of all dogs had declined penile amputation and scrotal urethrostomy. The CMCT were excised and primary reconstruction of the prepuce performed. Surgical lateral margins of 10, 20 or 30 mm were used and the deep margin excised the inner preputial lamina or underlying muscular fascia. The deep margin for caudoventral CMCT involved excision of the underlying SC adipose tissue. Preputial advancement was performed in 3/8 dogs to achieve adequate penile coverage. Histopathology confirmed all CMCT were Kiupel low grade, Patnaik grade II with complete margins in 6/8 dogs but identified metastasis only in one inguinal lymph node from one dog. Two dogs encountered minor complications (infection and a minor dehiscence) and one dog had a major complication (infection with major dehiscence). Median follow-up duration was 125 weeks, excluding one dog with 4 weeks of follow-up. None of the dogs experienced local recurrence or died of mast cell disease during the available follow-up period. Clinical relevance: This clinical study evaluated a surgical alternative to penile amputation and advanced reconstructive techniques for Kuipel low/Patnaik grade II preputial CMCT when these procedures were declined by owners. Surgical excision of preputial CMCT with lateral margins of 10, 20 or 30 mm with primary preputial reconstruction is achievable with low morbidity and a good outcome when penile amputation and scrotal urethrostomy is not an option.

Predesigned chimeric deep inferior epigastric perforator and inguinal lymph node flap for combined breast and lymphedema reconstruction: A comprehensive algorithmic approach

The combined use of a deep inferior epigastric perforator (DIEP) flap coupled with vascularized inguinal lymph nodes (VILNs) for simultaneous breast and lymphedema reconstruction has already been well established, and promising results have been reported. However, a standardized approach for the planning and shaping of this combined flap is still lacking. We aimed to propose a comprehensive algorithmic approach for delayed unilateral breast and lymphedema reconstruction using a predesigned abdominal flap associated with inguinal lymph node transfer. We present in detail the preoperative measurements and surgical technique of the chimeric flap, which combines a predesigned DIEP template and a preselected inguinal lymph node flap, based on the preoperative computed tomography angiography and SPEC-CT findings, respectively; four different flap types are described according to the location of the pedicles of the two flap components. Our results of a series of 34 consecutive female patients with unilateral mastectomy and arm lymphedema, who underwent this combined predesigned reconstructive procedure, are retrospectively analyzed and reported. We recorded a high survival rate of the chimeric flaps in our series, with only one case of partial ischemic loss of a DIEP skin island. In the majority of our patients, the pedicles of the combined flaps were located in opposite positions. After a mean 35-month follow-up, we recorded a 47% mean volume difference reduction of the lymphedematous compared to the unaffected arm; no donor-site lymphedema was documented. Self-evaluation questionnaires showed high patient satisfaction rates regarding breast reconstruction. This algorithmic approach provides standardized guidance for accurate design and transfer of the DIEP-VILN chimeric flap while achieving highly satisfactory outcomes for both breast and lymphedema reconstruction.

P127 Sphingosine-1-Phosphate Receptor Blockade with Etrasimod alters Lymphocyte Trafficking in Crohn's Disease: Insights from High-Dimensional Phenotypic Mapping

Abstract Background The blockade of lymphocyte trafficking from the lymph nodes (LNs) towards the intestinal mucosa is an effective approach for the treatment of ulcerative colitis (UC). Etrasimod is an oral, once-daily (QD), selective sphingosine 1-phosphate (S1P)1,4,5 receptor (S1PR) modulator, which is currently also under investigation for Crohn’s disease (CD). The therapeutic mechanism of action of S1PR modulators in the context of inflammatory bowel disease (IBD) is not completely understood. It is hypothesized that both B and T- cell populations are affected by this treatment and are retained in the peripheral LNs, reducing circulating lymphocytes and resulting in fewer immune cells available to traffic in the gastrointestinal tract. Etrasimod has been reported to induce a partial and selective reduction of lymphocyte subsets in the blood of healthy subjects, but the direct effect of S1PR modulators on LN leukocytes has not been evaluated. The aim of this study was to investigate changes in leukocyte subpopulations in peripheral LNs and peripheral blood (PB) in response to S1PR inhibition with etrasimod in patients with CD. Methods CD patients with moderate to severe disease activity, participating in the Phase 2, double-blinded, non-placebo-controlled portion of the CULTIVATE trial, were eligible for this sub-study. At baseline and after 14 weeks of etrasimod induction treatment (2 or 3 mg/day), 10cc of PB and 4 ultrasound guided biopsy samples of an inguinal LN were obtained. The isolated peripheral blood mononuclear cells (PBMCs) and LN leukocyte populations, were analyzed at single cell level via high-dimensional immunophenotyping through mass cytometry (CyTOF) at both timepoints. Results We observed that in the LNs, the numbers/percentages of naïve, central and effector memory T-helper cells, as well as, of CD8+ naïve T-cells were increased after treatment with etrasimod. There was a decrease in the proportion of these cell populations in peripheral blood. Circulating naïve and memory B-cells were reduced, while these subsets where also slightly reduced in the LN compartment. Innate immune cell populations were not significantly altered. Conclusion Etrasimod induction treatment resulted in an increase of both naïve and central memory T-lymphocyte subsets in inguinal LNs, with a corresponding decrease in the periphery. The effect on the frequency of B-cells was not consistent in the LNs and PB, while innate immunotypes and T-regs, were not significantly affected. Despite the limited sample size, these selective effects were consistent with previously published PB immunophenotyping studies with etrasimod. This study was conducted as a collaboration between Amsterdam UMC and Pfizer.

Gradual and synergistic correlation of tumor thickness and histological grade in penile invasive carcinomas

Histological grade and depth of invasion are among the best outcome pathological predictors in penile cancer. The TNM system is based on a combination of both for some stages. It is assumed that high-grade and deep tumors carry the worst prognosis, and the opposite occurs with superficial and low-grade neoplasms. However, there is no systematic evaluation of the phenomenon. We studied 147 patients from the Hospital de Oncologia - Instituto Mexicano del Seguro Social (period 2000 to 2013). They were treated by total or partial penectomies. Lymph node involvement was evaluated by bilateral inguinal node dissection (126 cases) or ultrasonography (21 cases). Tumor thickness was measured in mm from tumor surface to deepest invasion point, using a cut-point for superficial (≤10 mm) vs deep (>10 mm) tumors. Histological grade was from 1 to 3 according to WHO and AFIP criteria and considering G1 and G2 as low-grade and G3 as high-grade. Average age was 62 (26–98) years old. Tumor thickness mean was 15 mm (2–30 mm). G1, G2 and G3 tumors corresponded to 19 (13 %), 48 (33 %), and 80 (54 %) cases, respectively. Follow-up ranged from 10 to 82 months (median: 57 months). Fifty-three (36 %) patients died of disease. There was an overall correlation of tumor thickness and grade in most of the cases. Low-grade tumors were encountered in 92 % (12/13 cases) of superficial tumors. Deep tumors showed high-grade in 75 % of cases (73/97 cases). Superficial tumors with low histological grade had negative inguinal nodes and no mortality whereas deep tumors showing high histological grade were associated with high metastatic risk to lymph nodes (62/73 cases) and mortality (52/73 cases). Out of 24 deep tumors with low histological grade, seven had nodal spread (29 %) but only one died of disease. No outcome difference was found in HPV associated vs HPV independent tumors. Tumor thickness and grade are important synergistic and predictive pathological factors in relation to prognosis.