External Iliac Nodes Research Articles

Locoregional relapses in the ACCORD 12/0405-PRODIGE 02 study: Dosimetric study and risk factors

PurposeThe aim of this study is to correlate locoregional relapse with radiation therapy volumes in patients with rectal cancer treated with neoadjuvant chemoradiation in the ACCORD 12/0405-PRODIGE 02 trial. Patients and methodsWe identified patients who had a locoregional relapse included in ACCORD 12's database. We studied their clinical, radiological, and dosimetric data to analyze the dose received by the area of relapse. Results39 patients (6.5%) presented 54 locoregional relapses. Most of the relapses were in-field (n = 21, 39%) or marginal (n = 13, 24%) with only six out-of-field (11%), 14 could not be evaluated. Most of them happened in the anastomosis, the perirectal space, and the usual lymphatic drainage areas (presacral and posterior lateral lymph nodes). Only patients treated for a lower rectum adenocarcinoma had a relapse outside of the treated volume. 2 patients with T4 tumors extending into anterior pelvic organs had relapses in anterior lateral and external iliac lymph nodes. ConclusionsLowering the upper limit of the treatment field for low rectal tumors increased the risk of out of the field recurrence. For very low tumors, including the inguinal lymph nodes in the treated volume should be considered. Recording locoregional involvement, treated volumes, and relapse areas in future prospective trials would be of paramount interest to refine delineation guidelines.

Patterns of failure and implications for clinical target volume definition of locally advanced T4b rectal cancer identified with magnetic resonance imaging and treated using neoadjuvant chemoradiotherapy and surgery

Background and purposeElective irradiation of the external iliac lymph nodes (EIN) has always been advocated for T4b rectal cancer with anterior organ invasion without convincing evidence. This study aimed to explore the patterns of treatment failure for locally advanced T4b rectal cancer treated using neoadjuvant chemoradiotherapy (NCRT) and surgery. This information may help to clarify whether the current definition of the clinical target volume (CTV) is still appropriate. Materials and methodsWe retrospectively analyzed data from 126 patients with locally advanced T4b rectal cancer who received NCRT, without elective EIN irradiation, followed by surgery between January 2010 and October 2018. Pretreatment magnetic resonance imaging was used to identify the T4b disease in all cases. The locoregional recurrence (LRR) rate and EIN failure rate were evaluated, and the LRR locations were identified using a three-dimensional model. ResultsAfter a median follow-up of 53.9 months, LRR occurred in 11.1% of patients (14/126). All LRRs were located in the previously irradiated fields and below the S2–S3 junction. The EIN failure rate was 0.8% (1/126) among all patients and 1.8% (1/56) in the group with anterior genitourinary organ invasion. The estimated 4-year distant relapse-free survival, disease-free survival and overall survival were 79.3%, 73.2% and 86.9%, respectively. ConclusionsIt may be feasible to exclude the external iliac region from the CTV during NCRT for locally advanced T4b rectal cancer. However, further studies are needed to clarify whether the cranial border of the CTV can be lowered.

18F-FDG PET/CT Imaging in an Unusual Case of Cutaneous Melanoma Arising From Congenital Melanocytic Nevus in a Two-year-old Girl

Childhood malignant melanoma (MM) is extremely uncommon. We report an unusual case of cutaneous melanoma that developed from a medium-sized congenital melanocytic nevus (CMN) in a two-year-old girl. The patient had a history of CMN on the right hip, and she presented with a new ulcerative area with irregular borders and bleeding on CMN. Histopathological examination of the nevus revealed a MM. 18Florfluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography was performed for metastatic evaluation. The scan demonstrated metastatic increased 18F-FDG uptake in the right external iliac and inguinal lymph nodes.

MO221ONLY A SIMPLE CASE OF AKI IN AN ONCOLOGIC PATIENT?

Abstract Background Nivolumab is a drug belonging to the class of Immune Checkpoint Inhibitors (ICPI), the use of which has improved the prognosis for patients with various advanced malignancies. These agents are associated with several "immune-mediated" adverse effects, although the literature on Nivolumab renal toxicity is poor and anecdotal. A rare immune-mediated renal adverse event is acute interstitial nephritis (AIN) that often imposes Nivolumab suspension. Case report We present the case of a 75-year-old woman with stage IV melanoma (inguinal and external iliac lymph node metastases without localization of the primitive lesion). At diagnosis, renal function was normal by age (Creatinine 0.89 mg/dl; CKD EPI eGFR 71 ml/min/1.73 m2). After lymphadenectomy, an adjuvant treatment with Nivolumab was initiated. At 4-month follow-up, the patient was hospitalized for AKI (creatinine 2.6 mg/dl; eGFR 17,3 ml/min/1.73 m2). Although, renal function decline was not accompanied by signs of systemic immunoactivation, Nivolumab was suspended. In the following weeks, only a partial renal function recovery was observed, still limiting immunotherapy reintroduction. Thus, the patient was referred to our Onconephrology Outpatient Unit for a multidisciplinary approach. We performed a urinalysis with microscopy study of the sediment and observed rare dysmorphic red blood cells and leukocytes. To exclude a glomerulopathy, a comprehensive screening for autoimmune diseases and 24 hours proteinuria were also measured and found not significant (Table 1). Renal ultrasound did not show any relevant alteration. Based on our original suspicion of AIN, although in absence of an history of fever, rush or eosinophilia, we introduced Prednisone 25 mg/day. In the following weeks, blood and urine tests showed a significant improvement in renal function (serum creatinine 1.06 mg/dL, eGFR CKD-EPI 51 mL/min/1.73m2) and the absence of red blood cells, leukocytes and proteinuria in the urinalysis. Based on nephrologist advice, the patient was then able to resume the cancer treatment with a maintenance dose of prednisone equal to 5 mg/day. Conclusion AIN is a rare adverse effect of ICPIs that mandates the close monitoring of renal function in patients under immunotherapy with these agents. AKI occurrence in patients treated with ICPIs should always lead to investigate a possible AIN, even in the absence of the classic symptom set of fever, rush and eosinophilia and with minimal changes in urinalysis. Based on our single observation, and after an accurate literature review, we suggest the initiation of a corticosteroid treatment in oncologic patients on an ICPI complicated with AKI and with suspicion of AIN at urinalysis. Moreover, this case report thickens the importance of a multidisciplinary approach to oncologic patients not only when a conventional nephrotoxic chemotherapy has to be started, but also in case of ICIPs use. The nephrologist advice, in fact, could be useful in both preventing and treating severe renal complications such as AIN, also allowing the oncologic therapy maintenance.

Sarcoid‐like reaction of the extrathoracic lymph node in a patient with lung adenocarcinoma treated with pembrolizumab

Immune checkpoint inhibitors (ICIs) have become the standard of care for the treatment of non‐small cell lung cancer (NSCLC). With the increasing use of ICIs, clinicians should be familiar with their immune‐related adverse events, including sarcoid‐like reactions, which have been associated with the use of ICIs in patients with cancer. Sarcoid‐like reactions are caused by uncontrolled T helper 1‐mediated immune responses resulting from ICIs, but their pathophysiology is not fully understood. Sarcoid‐like reactions are often clinically important because they mimic metastases from treated cancer. According to previous reports, sarcoid‐like reactions are typically observed in intrathoracic locations (lung and/or mediastinal lymph nodes) and the skin. In this study, we report an extremely rare case of extrathoracic sarcoid‐like reaction in the right external iliac lymph node following two cycles of pembrolizumab therapy in a patient with lung adenocarcinoma. The laboratory data and computed tomography images suggested that infectious and autoimmune diseases were not considered to be the causative agents. Residual bone metastasis might have caused T helper 1‐mediated immune responses by pembrolizumab, and contributed to sarcoid‐like reactions in the right external iliac lymph node. Sarcoid‐like reactions should be considered in the differential diagnosis of patients with lung cancer treated with ICIs who exhibit worsening extrathoracic lymph node swelling. Clinicians should be cautious not to mistake extrathoracic sarcoid‐like reactions of the lymph nodes for progression of the treated disease.

Clinicopathological features and prognosis of nodal nevi

Objective: To investigate the clinicopathological characteristics, differential diagnosis and prognosis of nodal nevi (NN). Methods: Eighteen cases of NN diagnosed at Fudan University Shanghai Cancer Center, Shanghai, China from 2009 to 2019 were collected. The clinicopathological characteristics and follow-up data were retrospectively analyzed. Histopathologic evaluation and immunohistochemical studies were carried out. The Vysis Melanoma FISH Probe Kit, combined with 9p21(CDKN2A) and 8q24(MYC) assays were performed in 2 cases. Results: There were 2 males and 16 females in the case series. The age of the patients ranged from 36 to 70 years (average 48.2 years). Fifteen cases located in axillary lymph nodes, 1 in inguinal lymph node, 1 in cervical lymph node, and 1 in external iliac lymph node. NN was found in only one lymph node in each case. Histologically, the nevus cell aggregates were found in capsule of lymph nodes in all cases. Nevus cells grew along the capsule into trabeculae in 8 cases, with 3 of them scattered in parenchyma. In one of these 8 cases, nevus cell aggregates massively occupied the parenchyma of the lymph node. The largest lesions in the 18 NN cases measured from 0.2 to 6.5 mm. All of the NN cases were classified as conventional nevi. The majority of the cases were composed of uniform nevus-like cells and identical to cutaneous pigmented nevi without atypia, necrosis, or mitosis. In the NN case that massively occupied parenchyma, some areas had abundant nevus cells and displayed atypical cytologic features, including increased nucleo-cytoplasmic ratio, small nucleoli, and occasional mitotic figures. Immunohistochemistry was performed in 13 cases. All of them were positive for S-100, SOX10, Melan A, and p16. HMB45 showed weak staining in rare cells of only one case out of 13 cases. Ki-67 labeling index <1% was found in all 13 cases. Additionally, the results of FISH assay were both negative. All patients were followed up for 13 to 129 months (median 31.5 months). Except that one patient died of the salivary gland carcinoma, the other patients all survived without tumor during the follow-up period. Conclusions: NN is a benign melanocytic lesion in lymph node. It is important to distinguish NN from metastatic melanoma when nevus cells occur in parenchyma and subcapsular sinus of lymph nodes, or show some atypical cytologic features. The morphology of bland nevus cells in capsule and trabeculae is a valuable clue. Besides, immunohistochemical profiling and FISH assay are helpful in the differential diagnosis.

Clinical parameters and nomograms for predicting lymph node metastasis detected with 68 Ga-PSMA-PET/CT in prostate cancer patients candidate to definitive radiotherapy.

Defining the extent of disease spread with imaging modalities is crucial for therapeutic decision-making and definition of treatment. This study aimed to investigate whether clinical parameters and nomograms predict prostate-specific membrane antigen (PSMA)-positive lymph nodes in treatment-naïve nonmetastatic prostate cancer (PC) patients. The clinical data of 443 PC patients (83.3% high-risk and 16.7% intermediate-risk) were retrospectively analyzed. Receiver operating characteristic (ROC) curves with areas under the curve (AUC) were generated to evaluate the accuracy of clinical parameters (prostate-specific antigen [PSA], T stage, Gleason score [GS], International Society of Urological Pathology [ISUP] grade) and nomograms (Roach formula [RF], Yale formula [YF], and a new formula [NF]) in predicting lymph node metastasis. The AUCs of the various parameters and clinical nomograms were compared using ROC and precision-recall (PR) curves. A total of 288 lymph node metastases were identified in 121 patients (27.3%) using 68 Ga-PSMA-11-positron emission tomography (PET)/computed tomography (CT). Most PSMA-avid lymph node metastases occurred in external or internal iliac lymph nodes (142; 49.3%). Clinical T stage, PSA, GS, and ISUP grade were significantly associated with PSMA-positive lymph nodes according to univariate logistic regression analysis. The PSMA-positive lymph nodes were more frequently detected in patients with PSA >20 ng/ml, GS ≥7 or high risk disease compared to their counterparts. The clinical T stage, serum PSA level, GS, and ISUP grade showed similar accuracy in predicting PSMA-positive metastasis, with AUC values ranging from 0.675 to 0.704. The median risks for PSMA-positive lymph nodes according to the RF, YF, and NF were 31.3% (range: 12.3%-100%), 22.3% (range: 4.7%-100%), and 40.5% (range: 12.3%-100%), respectively. The AUC values generated from ROC and PR curve analyses were similar for all clinical nomograms, although the RF and YF had higher accuracy compared to NF. The clinical T stage, PSA, GS, and ISUP grade are independent predictors of PSMA-positive lymph nodes. The RF and YF can be used to identify patients who can benefit from 68 Ga-PSMA-11 PET/CT for the detection of lymph node metastasis. Together with nomograms, 68 Ga-PSMA-11 PET/CT images help to localize PSMA-positive lymph node metastases and can thus assist in surgery and radiotherapy planning.

P039 Muscle wasting &amp; weakness: a rare presentation of sarcoidosis

Background/Aims Sarcoidosis is a rare multisystem disease characterised by the presence of noncaseating granulomas. It most commonly affects the lungs though can affect any other organ system. Rarely, it can manifest as an acute myopathy. We describe a case of a patient presenting with muscle weakness and constitutional symptoms who was eventually diagnosed with sarcoidosis. Methods A 48-year-old male with a background of lumbar spondylosis and BPH, presented with a 6-week history of progressive upper and lower limb weakness, myalgia and reduced mobility. He also described an 18-month history of progressive fatigue, drenching night sweats and 10-kilogram weight loss. His symptoms meant he was unable to work as a firefighter. Examination demonstrated profound muscle wasting and reduced power in the proximal muscles of his upper and lower limbs. There was no evidence of rash, synovitis or lymphadenopathy. Blood tests showed a normocytic anaemia (Hb 100 g/L) and raised C-reactive peptide (180 mg/L) and erythrocyte sedimentation rate (100 mm/hour). The creatine kinase ranged between 20-42 units/litre. He had a weakly positive anti-nuclear antibody (1:80). The remaining autoantibody screen was negative including ENA, DSDNA, ANCA, rheumatoid factor and anti-CCP. Complement proteins were unremarkable. Furthermore, an extended myositis panel revealed no myositis-specific or myositis-associated antibodies. Serum calcium and angiotensin-converting enzyme (ACE) levels were normal. Blood cultures and virology screen including for HIV, hepatitis B, hepatitis C, CMV, EBV, COVID-19 and respiratory viruses were all negative. A chest radiograph was also unremarkable. Results He subsequently underwent electromyography which revealed generalised myopathy. An MRI of the lower limb proximal musculature showed evidence of muscle oedema worse on the right-side but no definitive evidence of myositis. A PET-CT followed revealing FDG-avid generalised lymphadenopathy and polyarticular uptake, but little uptake in the skeletal muscles. He underwent an external iliac lymph node core biopsy which demonstrated multiple noncaseating granulomas and lymphadenitis. Cultures for Tuberculosis were negative and there was no evidence of a lymphoproliferative disorder. A muscle biopsy was desired but not possible due to lack of availability because of the COVID-19 pandemic. The patient was diagnosed with sarcoidosis and commenced on three pulses of intravenous methylprednisolone followed by a weaning regimen of high-dose oral prednisolone and subcutaneous methotrexate. This resulted in a sustained improvement in his symptoms and normalisation of inflammatory markers. Conclusion Symptomatic myopathy is present in only 0.5-2.5% of sarcoidosis patients. This unique case highlights the heterogeneity of this disease and the vital role different diagnostic modalities play in achieving the correct diagnosis. It is also pertinent that the lymphadenopathy, found incidentally via imaging, led to the diagnosis. Although notoriously a diagnosis of exclusion, this case emphasises the importance of considering sarcoidosis even in the absence of respiratory symptoms, a raised ACE or hypercalcaemia. Disclosure C. Tomlinson: None. A. Khan: None. D. Mukerjee: None. N. Bhadauria: None.

Limited versus Extended Pelvic Lymph Node Dissection for Prostate Cancer: A Randomized Clinical Trial

BackgroundPelvic lymph node dissection (PLND) is the most reliable procedure for lymph node staging. However, the therapeutic benefit remains unproven; although most radical prostatectomies at academic centers are accompanied by PLND, there is no consensus regarding the optimal anatomical extent of PLND. ObjectiveTo evaluate whether extended PLND results in a lower biochemical recurrence rate. Design, setting, and participantsWe conducted a single-center randomized trial. Patients, enrolled between October 2011 and March 2017, were scheduled to undergo radical prostatectomy and PLND. Patients were assigned to limited or extended PLND by cluster randomization. Specifically, surgeons were randomized to perform limited or extended PLND for 3-mo periods. InterventionRandomization to limited (external iliac nodes) or extended (external iliac, obturator fossa and hypogastric nodes) PLND. Outcome measurements and statistical analysisThe primary endpoint was the rate of biochemical recurrence. Results and limitationsOf 1440 patients included in the final analysis, 700 were randomized to limited PLND and 740 to extended PLND. The median number of nodes retrieved was 12 (interquartile range [IQR] 8–17) for limited PLND and 14 (IQR 10–20) extended PLND; the corresponding rate of positive nodes was 12% and 14% (difference −1.9%, 95% confidence interval [CI] −5.4% to 1.5%; p = 0.3). With median follow-up of 3.1 yr, there was no significant difference in the rate of biochemical recurrence between the groups (hazard ratio 1.04, 95% CI 0.93–1.15; p = 0.5). Rates for grade 2 and 3 complications were similar at 7.3% for limited versus 6.4% for extended PLND; there were no grade 4 or 5 complications. ConclusionsExtended PLND did not improve freedom from biochemical recurrence over limited PLND for men with clinically localized prostate cancer. However, there were smaller than expected differences in nodal count and the rate of positive nodes between the two templates. A randomized trial comparing PLND to no node dissection is warranted. Patient summaryIn this clinical trial we did not find a difference in the rate of biochemical recurrence of prostate cancer between limited and extended dissection of lymph nodes in the pelvis.This study is registered on ClinicalTrials.gov as NCT01407263.

Equivalent dose in 2 Gy (EQD2) to pelvic lymph nodes using volume based prescription for three brachytherapy applicators - a dosimetric retrospective analysis.

BackgroundPelvic lymph node (PLN) metastasis has been included in the FIGO staging, so there is a need to determine the dose contribution from brachytherapy to ascertain the total delivered dose to the pelvic lymph nodes in cervical cancer. The aim of the study was to calculate the equivalent dose in 2 Gy (EQD2) of the pelvic lymph nodes (PLNs) based on volume prescription using three applicators.Materials and methodsForty-one patients who had undergone external beam radiotherapy followed by brachytherapy using tandem ovoids (TO), tandem ring (TR) and TO + free hand interstitial needles (TO + FH) applicators were taken for this study. 26 Gy in 4 fractions was prescribed to HRCTV. The external iliac node (ELN), internal iliac node (ILN) and obturator (OBT) were contoured and the median EQD2 of the lymph nodes was calculated.ResultsThe median bilateral EQD2 values of ELN were 1.55 Gy (TR), 1.75 Gy (TO), 1.9 Gy (TO + FH), of ILN these were 2.57 Gy (TR), 3.27 Gy (TO), 3.04 Gy (TO + FH), and of OBT these were 3.69 Gy (TR), 4.46 Gy (TO), 4.69 Gy (TO + FH), respectively. The total median EQD2 values of TR, TO and TO + FH were 52.71 Gy, 53.03 Gy, and 53.88–62.73 Gy, respectively.ConclusionOur study calculated the median EQD2 to the pelvic lymph nodes using three types of applicators in brachytherapy. This could serve as reference to decide on the EBRT boost dose while treating patients with enlarged pelvic lymph nodes.

Prospective observational study evaluating acute and delayed treatment related toxicities of prophylactic extended field volumetric modulated arc therapy with concurrent cisplatin in cervical cancer patients with pelvic lymph node metastasis.

To evaluate the treatment related acute and delayed toxicities of extended field Volumetric modulated arc therapy (VMAT) with concurrent chemotherapy in patients of locally advanced cervical cancer with pelvic lymph nodes. From 2014 to 2016, 15 patients of locally advanced cervical cancer with Fluoro-deoxyglucose positron emission tomography (FDG-PET) positive pelvic lymph nodes were treated with extended field Simultaneous integrated boost (SIB)-VMAT 45 Gy/55 Gy/25#/5weeks and concurrent cisplatin. Acute toxicities were documented according to common terminology criteria for adverse events version 4 (CTCAE v.4). Dose volume parameters and patient characteristics were analyzed for association with toxicities. Median age of patients at diagnosis was 48 years. 40% (6 patients) were stage IIB & 60% (9 patients) were stage IIIB. Median number of involved pelvic lymph nodes was 2 (range, 1-4), commonest location was external iliac lymph node region (86%). Median number of concurrent chemotherapy cycles received was five. Treatment was well tolerated and there were no grade ≥ 3 acute toxicities. Commonest acute toxicities observed were vomiting (≥grade2 -13.3%) followed by & nausea (grade ≥ 2 in 6%) and were associated with volume of bowel bag receiving 45 Gy. Constitutional symptoms (≥grade 2) were observed in 6% patients and had no dosimetric associations. At a median follow up of 43 months, delayed ≥ grade1, 2, 3 toxicity were observed in 80%, 0%, and 0% respectively with diarrhea being the commonest. Prophylactic para aortic extended field VMAT with concurrent chemotherapy for locally advanced cervical cancer is well tolerated with acceptable acute toxicity profile. Significant grade 3 acute/delayed toxicities were not observed in this cohort of patients.

Late testicular relapse two decades after primary extragonadal germ cell tumor with uncommon metastases: a case report

BackgroundExtragonadal germ cell tumor (EGCT) is a relatively rare condition, reportedly representing 3–7% of all germ cell tumors. We report a patient who had metachronous testicular tumor with uncommon metastases 20 years after primary retroperitoneal EGCT treatment, along with a corresponding literature review.Case presentationA 49-year-old Japanese man visited our department in November 2017 with chief complaints of indolent right scrotum enlargement and a right inguinal mass. History showed that the patient visited our department of gastroenterology with chief complaints of blackish feces and ill complexion in February 1997. Computed tomography (CT) showed a right retroperitoneal tumor, which was removed in the same month. Histopathological examination showed a teratoma and yolk sac tumor. He was diagnosed with primary retroperitoneal EGCT and received three courses of chemotherapy (bleomycin/etoposide/cisplatin; BEP). Periodic imaging and the determination of tumor markers (alpha-fetoprotein [AFP], human chorionic gonadotropin [HCG], and lactate dehydrogenase [LDH]) showed no recurrence or metastasis during the 5 years postoperatively. Subsequently, he did not visit the outpatient ward. In August 1999, he underwent surgery of right hydrocele. Contrast-enhanced CT showed a 35-mm contrast effect with uneven content in the right testicle and enlarged nodes that raised suspicion for metastases in the right inguinal and right external iliac lymph nodes. All tumor markers were within normal ranges. He underwent right high orchiectomy and resection of the right inguinal lymph nodes in the same month. Histopathological findings revealed seminoma (pT1, pN2, M0, S0, and TNM stage IIB). He received postoperative chemotherapy, one course of BEP therapy, and three courses of etoposide and cisplatin therapy. Post-chemotherapy CT confirmed a complete clinical response at the right external iliac lymph nodes, and this response continued 12 months later. No recurrence or metastasis has been found so far.ConclusionsWe report a patient in whom a testicular tumor with uncommon metastases occurred 20 years after primary retroperitoneal EGCT treatment. After EGCT treatment, testicular relapses tend to occur after relatively long-term follow-up. After EGCT treatment, such patients must be closely monitored for testicular recurrences and onset of testicular tumor.

Prospective Non-randomized Control Trial on Role of Systematic High Para-Aortic Lymphadenectomy in Endometrial Cancer: Indian Study

Endometrial cancer (EC) accounts for approximately 10% of all cancers in females and is the second most common gynecologic cancer. The primary goal of surgical staging in EC is to identify extrauterine disease. Pelvic and para-aortic lymph node dissection (PLND and PaLND) is the gold standard in the detection of lymph node metastases in EC. However, there is still no uniformity worldwide regarding the scope and extent of lymph node dissection in EC. The present prospective non-randomized study was conducted to establish the importance of systematic lymphadenectomy (LND), especially PaLND above the inferior mesenteric artery (IMA), and to identify the risk factors associated with lymph node metastasis. A total of 210 patients with EC were included. All patients underwent comprehensive surgical staging which included simultaneous PLND and PaLND. In addition for non-endometrioid, additional omental and peritoneal biopsies were also performed. PLND consisted of complete removal of common iliac, external iliac, internal iliac and obturator lymph nodes as per standard techniques. The extent of PaLND was up to the renal veins. Pelvic lymph nodes (PLN), para-aortic lymph nodes (PaLN) harvested below the IMA and PaLN dissected above the IMA were labeled separately and submitted for histopathological examination (HPE). Patient’s demographic factors, surgical outcomes and tumor histological findings were tabulated for analysis. Patients diagnosed with EC were most commonly in their seventh decade (59.5%). The mean time for LND was 35 min. In 66% of the cases with positive PLN, the PaLN was also positive. Twenty-nine (13.8%) patients had both PLN and PaLN involvement. In all cases of positive PaLN, the nodes between IMA and renal veins were the only positive nodes. In 15 (7.1%) patients, PaLN were the only positive nodes. The mean PaLN yield was 9.1. Predictors of PaLN positivity were pelvic node positivity, Grade III tumors and lymphovascular space invasion (LVSI). Major complications observed were wound infection, paralytic ileus and subacute intestinal obstruction. In oncology, a good loco-regional control has the greatest impact on survival. Systematic para-aortic lymphadenectomy done with good surgical technique results in minimal morbidity and mortality without any additional blood transfusion requirement. The trend toward greater use of complete surgical staging has been accompanied by a judicious use of adjuvant therapy. This has led to marked decrease in the use of pelvic radiation therapy and its complications and has a significant impact on the cost of treatment.

This Month in Adult Urology

This Month in Adult Urology

Patterns of Locoregional Recurrence after Radical Cystectomy for Stage T3-4 Bladder Cancer: A Radiation Oncologist's Point of View.

PurposeAdjuvant radiotherapy (RT) has been performed to reduce locoregional failure (LRF) following radical cystectomy for locally advanced bladder cancer; however, its efficacy has not been well established. We analyzed the locoregional recurrence patterns of post-radical cystectomy to identify patients who could benefit from adjuvant RT and determine the optimal target volume.Materials and MethodsWe retrospectively reviewed 160 patients with stage ≥ pT3 bladder cancer who were treated with radical cystectomy between January 2006 and December 2015. The impact of pathologic findings, including the stage, lympho-vascular invasion, perineural invasion, margin status, nodal involvement, and the number of nodes removed on failure patterns, was assessed.ResultsMedian follow-up period was 27.7 months. LRF was observed in 55 patients (34.3%), 12 of whom presented with synchronous local and regional failures as the first failure. The most common failure pattern was distant metastasis (40%). Among LRFs, the most common recurrence site was the cystectomy bed (15.6%). Patients with positive resection margins had a significantly higher recurrence rate compared to those without (28% vs. 10%, p=0.004). The pelvic nodal recurrence rate was < 5% in pN0 patients; the rate of recurrence in the external and common iliac nodes was 12.5% in pN+ patients. The rate of recurrence in the common iliac nodes was significantly higher in pN2?? patients than in pN0?? patients (15.2% vs. 4.4%, p=0.04).ConclusionPelvic RT could be beneficial especially for those with positive resection margins or nodal involvement after radical cystectomy. Radiation fields should be optimized based on the patient-specific risk factors.

Impact on lower limb lymphedema of pelvic lymphadenectomy with external iliac lymph nodes left-opened distal lymphatics technique.

The aim of this study was to investigate the effect of maintaining opened distal lymphatic vessels of external iliac lymph nodes on lymphedema and lymphocyst formation of lower limbs after pelvic lymphadenectomy. Prospective single center observational study was carried out in 83 patients with gynecological malignancies who underwent pelvic lymphadenectomy. During the operation, the distal lymphatic vessels of the external iliac lymph nodes were cut off by an ultrasound scalpel or scissors, and the proximal end was closed by bipolar coagulation. The patients were re-examined by a physical examination, ultrasound examination and inquiry of the symptoms within 2 years after the operation to check whether they had lower limb lymphedema and to analyze the presence of lymphedema and lymphocyst of lower limbs and the risk. The incidence of lower limb lymphedema (LLL) was 21.6% (18/83). Among the patients with LLL, 5.5% (1/18) was diagnosed with stage 0 according to the criteria of International Society of Lymphology, 83.3% (15/18) with stage 1, and 11.1% (2/18) with stage 2. Presently, there was no lymphedema diagnosed at stage 3. The incidence of lymphocyst was 7.2% (6/83). Among the patients with lymphocyst, 3.6% (3/83) occurred 1 month after operation, 2.4% (2/83) occurred 3 months after operation and 1.2% (1/83) occurred 6 months after operation. Patients with radiotherapy and abdominal infection were more likely to suffer from LLL (P<0.05). Maintaining opened distal lymphatic vessels of external iliac lymph nodes during pelvic lymphadenectomy is feasible, safe and with a 21.6% and 7.2% of potential lymphedema and lymphocists, respectively.

Extended Versus Limited Pelvic Lymph Node Dissection During Radical Prostatectomy for Intermediate- and High-risk Prostate Cancer: Early Oncological Outcomes from a Randomized Phase 3 Trial

BackgroundThe role of extended pelvic lymph node dissection (EPLND) in the surgical management of prostate cancer (PCa) patients remains controversial, mainly because of a lack of randomized controlled trials (RCTs). ObjectiveTo determine whether EPLND has better oncological outcomes than limited PLND (LPLND. Design, setting and participantsThis was a prospective, single-center phase 3 trial in patients with intermediate- or high-risk clinically localized PCa. InterventionRandomization (1:1) to LPLND (obturator nodes) or EPLND (obturator, external iliac, internal iliac, common iliac, and presacral nodes) bilaterally. Outcome measurements and statistical analysisThe primary endpoint was biochemical recurrence–free survival (BRFS). Secondary outcomes were metastasis-free survival (MFS), cancer-specific survival (CSS), and histopathological findings. The trial was designed to show a minimal 15% advantage in 5-yr BRFS by EPLND. Results and limitationsIn total, 300 patients were randomized from May 2012 to December 2016 (150 LPLND and 150 EPLND). The median BRFS was 61.4 mo in the LPLND group and not reached in the EPLND group (hazard ratio [HR] 0.91, 95% confidence interval [CI] 0.63–1.32; p = 0.6). Median MFS was not reached in either group (HR 0.57, 95% CI 0.17–1.8; p = 0.3). CSS data were not available because no patient died from PCa before the cutoff date. In exploratory subgroup analysis, patients with preoperative biopsy International Society of Urological Pathology (ISUP) grade groups 3–5 who were allocated to EPLND had better BRFS (HR 0.33, 95% CI 0.14–0.74, interaction p = 0.007). The short follow-up and surgeon heterogeneity are limitations to this study. ConclusionThis RCT confirms that EPLND provides better pathological staging, while differences in early oncological outcomes were not demonstrated. Our subgroup analysis suggests a potential BCRFS benefit in patients diagnosed with ISUP grade groups 3–5; however, these findings should be considered hypothesis-generating and further RCTs with larger cohorts and longer follow up are necessary to better define the role of EPLND during RP. Patient summaryIn this study, we investigated early outcomes in prostate cancer patients undergoing prostatectomy according to the anatomic extent of lymph node resection. We found that extended removal of lymph nodes did not reduce biochemical recurrence of prostate cancer in the expected range.

Effects of Green Tea on Various Types of Indolent Low Grade B-Cell Lymphomas

Low grade B cell neoplasms, such as chronic lymphocytic leukemia (CLL), usually are asymptomatic when diagnosed and undergo close observation. Many patients with low grade B cell lymphomas and leukemias (LGBCL) appreciate reassurance that not treating at time of diagnosis is the appropriate management. Society has long focused on diet and lifestyle changes as an alternative to medication; however, there is limited data to which these changes can assist with hematologic disorders. Green tea (GT) has been studied in regard to its effects on longevity and health. A cohort study followed 52,000 adults over 13 years and found that the frequency of GT consumption was inversely associated with risk of total hematologic neoplasms (Takada M, et al., 2019). There are several other studies that report key oncologic pathways are disrupted by a compound found in GT called epigallocatechin-gallate (EGCG) (Farooqi A, et al., 2020). Following a case series publication by Dr. Shanafelt, the National Cancer Institute sponsored clinical trials through the Mayo Clinic, evaluating EGCG in 42 patients with asymptomatic CLL. Patients received 2000mg EGCG twice daily for 6 months. Results showed 69% of patients had a biological response with greater than 20% reduction in absolute leukocyte count (ALC) and/or greater than 30% in reduction in size of the lymph node area utilizing standard assessment criteria (Shanafelt T. et al. 2013). This data encouraged our practice to recommend to patients to drink two bags of GT in steamy hot water daily. We studied 11 patients with indolent CLL, follicular lymphoma (FL), Waldenstrom macroglobulinemia (WM), monoclonal gammopathy of undetermined significance (MGUS), and splenic Marginal zone lymphoma (MZL). No patient was symptomatic. Disease makers were recorded over time during their routine visits for observation. The markers used were ALC for CLL and MZL, standardized uptake value (SUV) on PET scan for lymph node detection for FL, immunoglobulin level as well as monoclonal protein (M-protein) measured by SPEP for MGUS, and IgM and M-protein for WM. One patient with extensive cutaneous plaque psoriasis had routine skin checks. The results were recorded in the electronic health record over varying time periods based on patient presentation and follow up. Six patients with CLL responded to GT, with reductions in ALC. In patient 1, ALC decreased by 37% over 48 months. Patient 2's ALC decreased by 68% over 102 months. Patient 3's ALC decreased by 74% in 96 months. Patient 4 had a drastic increase in ALC from 23,900 to 72,400 over three years before GT. Once starting GT, his ALC plateaued at 72,000 and has remained stable for 65 months. Patient 5 had decrease ALC of 66% over 99 months. Patient 6 with WM had a 79% decrease in IgM over 65 months drinking GT. M-protein decreased by 81%. Patient 7 had a decrease in IgM by 26% and a 24% decrease in M-protein over 36 months. Patient 8 with MGUS had a decrease in IgG by 25% over 77 months. Patient 9 had a decrease in IgG by 23% with M-protein reduction of 43%. Due to compliance issues, duration of therapy was unknown. Patient 10 with ZL had an ALC reduction of 73% over 95 months. Lastly, patient 11 with FL and psoriasis was treated with GT for 23 months. There was a reduction of external iliac and inguinal lymph node SUV by 38% and 83% over 23 months, respectively. It was also noted of a significant improvement of extensive plaque psoriasis during this time on GT (Table 1). The 11 patients highlighted in the practice had improvement in biomarkers and lymphadenopathy during the time they took daily GT. The EGCG study at Mayo Clinic, in which CLL patients took up to 4,000mg of EGCG per day, had significant responses as well as adverse effects including transaminitis. This compares to the population in our study, which includes various types of LGBCL and MGUS that were taking at most 200mg of EGCG per day and had significant responses with no adverse effects. The use of low dose EGCG for inducing clinical improvement of these types of LGBCL and MGUS may be used to delay the onset of starting therapy, thus forestalling immunosuppressive treatment and associated toxicities. Larger randomized control trials involving other forms of indolent LGBCL and MGUS would be significant for the potential of GT being a safe, non-toxic lifestyle change that could benefit patients who do not require aggressive medical therapy for their neoplastic processes. Disclosures No relevant conflicts of interest to declare.

Rituximab Chemotherapy for Primary Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma of the Urinary Bladder : A Case Report

An 84-year-old man consulted a local physician for asymptomatic macrohematuria. Abdominal ultrasonography revealed thickening ofthe bladder wall from the triangular part ofthe bladder to the posterior wall, and he was referred to our department. Cystoscopy showed extensive bladder wall thickening with edema ofthe mucosa. Abdominal contrast-enhanced computed tomography (CT) showed extensive bladder wall thickening and right external iliac lymphadenopathy accompanied by a contrast effect suspected ofbeing extravesical invasion. We performed transurethral resection ofthe bladder tumor and made the diagnosis ofmucosa associated lymphoid tissue (MALT) lymphoma. Our diagnosis made from positron emission tomography-CT performed after surgery was primary MALT lymphoma of the bladder and metastasis to the right external iliac lymph node. We administered rituximab 375 mg/m2 once a week for four times in total. CT after rituximab administration showed that the tumor and right external iliac lymph nodes had shrunk significantly, and no recurrence was present at 18 months after treatment.

Impact of Pelvic Intensity-modulated Radiotherapy (IMRT) on Lymph Node Coverage and Dose to Critical Organs, Compare to Three-Dimensional Conformal Radiation Therapy (3D-CRT), in Localized High-Risk Prostate Cancer

Men with high risk prostate cancer (HR-PrCa) are typically treated with combined androgen deprivation therapy and curative radiotherapy (RT) consisting of pelvic nodal and prostate/seminal vesicle (PrSV) irradiation followed by PrSV boost RT. 3D-CRT or IMRT are used for the treatment of pelvic nodes. A phase II randomized study examining the effect of RT technique on patient Quality of Life (QoL) was completed in our institution. Here, we report an early analysis of the dosimetric impact of 3D-CRT versus IMRT in patients participating in this study. A total of 105 men with HR-PrCa were randomized at 1:1 ratio to receive either pelvic 3D-CRT (standard 4-field conformal technique) or multi-beam IMRT, consisting of 4500cGy in 25 fractions to planning target volume (PTV) 1, followed by boost RT to PTV2 of 2496cGy in 13 fractions. The latter was delivered using a 7-field IMRT in all patients. Organs at risk (OAR) and clinical target volumes (CTV) were delineated on CT simulation images. The lymph node target included the common, internal, external iliac, obturator and pre-sacral lymph nodes in accordance with RTOG guidelines. CTV1 consisted of nodal CTV plus PrSV. CTV2 was minimized to PrSV. The PTV consisted of an expansion of 7 mm beyond CTV. For consistency, in comparison between the two techniques, IMRT fields were modified to results to similar superior border coverage as 3D-CRT, at the level of L5-S1. Bladder and rectum were contoured as solid organs. To take inter-fractional bowel motion into account, bowel was delineated as whole pelvic and abdominal cavity excluding bones, muscle, and other OAR. Pelvic RT with 3DCRT missed significant percentage of pelvic nodal volume. PTV1 D95% showed mean difference of -4.96, 95% CI (-6.41, -1.74); p = 0.0013 and D99% showed mean difference of -11.56, 95% CI (-14.96, -8.17); p< 0.00001 in favor of IMRT. There was significant difference in PTV1 heterogeneity index (D2%-D95%/D50%) (Mean diff = 0.22, 95%CI (0.14, 0.29); P<0.00001). IMRT decreased dose to OAR. Rectum V30 was 97% in 3DCRT compare to 93.41% in IMRT arm with absolute difference of 3.81% (95% CI (1.52, 6.11); P = 0.0014). Bladder V40 and V50 were significantly reduced (V40: 84 % vs 62% for 3DCRT vs IMRT, absolute difference of 22% (95%, CI (15.55, 28.2); P<0.0001); V50 absolute reduction of 18% with IMRT (95%, CI (11.53, 24.48); P<0.0001). Similarly, IMRT reduced total body/bone irradiation significantly. This randomized study of 3D-CRT versus pelvic IMRT is an appropriate setting to investigate the dosimetric impact of pelvic IMRT and help define its potential benefits on patient QoL. This early analysis suggests that utilization of IMRT for pelvic RT could offer dosimetric advantages by improve lymph node coverage and reducing RT dose to OAR. The results are in agreement with an improved bowel-related QoL observed in this study. On-going analysis examines correlations between dosimetric and patient QoL data.