The Role of IONM in Reducing the Occurrence of Shoulder Syndrome Following Lateral Neck Dissection for Thyroid Cancer

Lateral neck dissection (LND) leads to a significant morbidity involving accessory nerve injury. Modified radical neck dissection (MRND) aims at preservation of the accessory nerve, but patients often present with negative functional outcomes after surgery. The role of neuromonitoring (IONM) in the prevention of shoulder syndrome has not yet been defined in comparison to nerve visualization only. We retrospectively analyzed 56 thyroid cancer patients who underwent MRND over a period of six years (2015–2020) in a high-volume institution. Demographic variables, type of surgical procedure, removed lymph nodes and the metastatic node ratio, pathology, adoption of IONM and shoulder functional outcome were investigated. The mean number of lymph nodes removed was 15.61, with a metastatic node ratio of 0.2745. IONM was used in 41.07% of patients, with a prevalence of 68% in the period 2017–2020. IONM adoption showed an effect on post-operative shoulder function. There were no effects in 89.29% of cases, and temporary and permanent effects in 8.93% and 1.79%, respectively. Confidence intervals and two-sample tests for equality of proportions were used when applicable. Expertise in high-volume centres and IONM during MRND seem to be correlated with a reduced prevalence of accessory nerve lesions and limited functional impairments. These results need to be confirmed by larger prospective randomized controlled trials.

116 PROGNOSTIC IMPACT OF THE SHORT-AXIS DIAMETER FOR THE NODAL ASSESSMENT BEFORE PREOPERATIVE CHEMOTHERAPY IN ESOPHAGEAL CANCER

Clinical N category (cN) is generally assessed by measuring the nodal diameter by CT before the initiation of primary treatment in esophageal squamous cell carcinoma (ESCC). The short-axis diameter is recommended for evaluating treatment response in solid tumors by RECIST. This study aimed to elucidate the prognostic implication of the maximum short-axis diameter of lymph node (cN-size) before preoperative chemotherapy for ESCC. Methods We enrolled a total of 152 patients who underwent preoperative cisplatin/5-fluorouracil therapy (CF) followed by esophagectomy from 2005 to 2011. There were 127 men and 25 women with a median age of 65 years (range: 47–79 years). Clinically metastatic node was defined as follows; the node with cN-size ≥10 mm or that with 5 mm ≤ cN-size <10 mm and contrast enhancement, round shape and/or central necrosis in CT before starting CF. The association between the maximum cN-size and the overall survival (OS) after surgery was statistically investigated. The median follow-up period was 87 months (range: 36–145 months). Results The number of patients with cN0 and cN1–3 was 60 and 92, respectively. Twenty-seven and 65 patients with cN1–3 were classified into cN-size <10 mm and cN-size ≥10 mm group, respectively. The 5-year OS rates in cN0, cN-size <10 mm and cN-size ≥10 mm groups were 70%, 51% and 45%, respectively (P = 0.006). Among Ut-Mt tumors, the OS in the cN-size <10 mm group was significantly worse than that in the cN0 group (5-year OS rate: 45% vs. 74%, P = 0.048). However, there were no significant differences in the OS between these two groups in Lt tumors (67% vs. 64%, P = 0.789). Conclusion The maximum short-axis diameter of lymph node before preoperative chemotherapy is significantly associated with OS in patients with ESCC. Lymph node with 5 mm ≤ cN-size <10 mm in the short axis should be treated as a metastatic node especially in Ut or Mt tumors, considering the poor prognosis.

Low endogenous testosterone levels are associated with the extend of lymphnodal invasion at radical prostatectomy and extended pelvic lymph node dissection

Objective To investigate clinical factors associated to lymphnodal metastasis load in patients who underwent to radical prostatectomy (RP) and extended pelvic lymph node dissection (ePLND). Materials and methods Between November 2014 and December 2019, ET was measured in 617 consecutive patients not under androgen deprivation therapy who underwent RP and ePLND. Lymphnode invasion (LNI) was codified as not present (N = 0) or with one (N = 1) or more than one metastatic node (N > 1). The risk of multiple pelvic lymph node metastasis (N > 1, mPLNM) was assessed by comparing it to the other two groups (N > 1 vs. N = 0 and N > 1 vs. N = 1). Then, we assessed the association between ET and lymphnode invasion for standard predictors, such as PSA, percentage of biopsy positive cores (BPC), tumor stage greater than 1 (cT > 1) and tumor grade group greater than two (ISUP > 2). Results Overall, LNI was detected in 70 patients (11.3%) of whom 39 (6.3%) with N = 1 and 31 (5%) with N > 1. On multivariate analysis, ET was inversely associated with the risk of N > 1 when compared to both N = 0 (odds ratio, OR 0.997; CI 0.994–1; p = 0.027) as well as with N = 1 cases (OR 0.994; 95% CI 0.989–1.000; p = 0.015). Conclusions In clinical PCa, the risk of mPLNM was increased by low ET levels. As ET decreased, patients had an increased likelihood of mPLNM. Because of the inverse association between ET and mPLNM, higher ET levels were protective against aggressive disease. The influence of locally advanced PCa with high metastatic load on ET levels needs to be explored by controlled trials.

Targeted Axillary Dissection after Chemotherapy: Feasibility Study with Clip and Carbon Dye Tattoo – Neotarget Trial

<b><i>Background:</i></b> Axillary staging in patients with complete response after neoadjuvant chemotherapy (NAC) is still controversial. Our objective was to test tattoo alone and subsequentially tattoo plus clip as markers in the targeted axillary dissection of ycN0 patients. <b><i>Methods:</i></b> Prospective cohort of cT1-T3, cN1 (proven histologically), M0 patients scheduled to receive NAC. Exclusion criteria were lobular histology, prior axillary surgery, and clinical N2/3. In cohort 1 this positive node (Neotarget node) was tattooed at diagnosis. If ycN0, a targeted axillary dissection was performed. After an interim analysis with negative results we changed the protocol in order to do a double marking procedure (Cohort 2): the positive node was clipped at diagnosis and after NAC a tattoo was done before surgery. <b><i>Results:</i></b> Thirteen patients in Cohort 1 and 18 patients in Cohort 2. Failure to identify the Neotarget node with multiple nodes retrieved in 9/13 (69%) of Cohort 1 patients. Also in 5/13 (38%) of Cohort 1 patients and 3/18 (17%) of Cohort 2 there was a failure to clearly identify tattooed nodes. In Cohort 2, clip identification by surgical specimen radiography allowed the identification of the tagged node in 17/18 (94,4%) of cases. The concordance between the clipped node and sentinel nodes was 16/18 (89%). <b><i>Conclusions:</i></b> The introduction of double marking by clipping the metastatic node and verifying their removal by surgical specimen radiography, using carbon ink as a tracer, allowed the identification of the metastatic node in 94% of cases, with a simple, reproducible, and easy-to-implement targeted axillary dissection procedure.

Should Lymph Nodes Be Retrieved in Patients with Intrahepatic Cholangiocarcinoma? A Collaborative Korea–Japan Study

Background: This study was performed to investigate the oncologic role of lymph node (LN) management and to propose a surgical strategy for treating intrahepatic cholangiocarcinoma (IHCC). Methods: The medical records of patients with resected IHCC were retrospectively reviewed from multiple institutions in Korea and Japan. Short-term and long-term oncologic outcomes were analyzed according to lymph node metastasis (LNM). A nomogram to predict LNM in treating IHCC was established to propose a surgical strategy for managing IHCC. Results: A total of 1138 patients were enrolled. Of these, 413 patients underwent LN management and 725 did not. A total of 293 patients were found to have LNM. The No. 12 lymph node (36%) was the most frequent metastatic node, and the No. 8 lymph node (21%) was the second most common. LNM showed adverse long-term oncologic impact in patients with resected IHCC (14 months, 95% CI (11.4–16.6) vs. 74 months, 95% CI (57.2–90.8), p < 0.001), and the number of LNM (0, 1–3, 4≤) was also significantly related to negative oncologic impacts in patients with resected IHCC (74 months, 95% CI (57.2–90.8) vs. 19 months, 95% CI (14.4–23.6) vs. 11 months, 95% CI (8.1–13.8)), p < 0.001). Surgical retrieval of more than four (≥4) LNs could improve the survival outcome in resected IHCC with LNM (13 months, 95% CI (10.4–15.6)) vs. 30 months, 95% CI (13.1–46.9), p = 0.045). Based on preoperatively detectable parameters, a nomogram was established to predict LNM according to the tumor location. The AUC was 0.748 (95% CI: 0.706–0.788), and the Hosmer and Lemeshow goodness of fit test showed p = 0.4904. Conclusion: Case-specific surgical retrieval of more than four LNs is required in patients highly suspected to have LNM, based on a preoperative detectable parameter-based nomogram. Further prospective research is needed to validate the present surgical strategy in resected IHCC.

A prospective study of dual-energy CT in determining the metastatic and non-metastatic lymph nodes of colorectal cancer

Background To explore the ability of Dual-energy CT (DECT) to differentiate metastatic from non-metastatic lymph nodes in colorectal cancer (CRC). Methods Seventy-one patients with primary CRC underwent contrast-enhanced DECT imaging before surgery. The colorectal specimen was scanned after surgery, and lymph nodes were matched to the pathology report. The DECT quantitative parameters were analyzed: dual-energy curve slope value(λHU), standardized iodine concentration (n△HU), iodine water ratio (nIWR), electron density value (nρeff), and effective atom-number (nZ), for the metastatic and non-metastatic lymph node differentiation. Also, sensitivity and specificity analyses were performed by using receiver operating characteristic curve. Results One hundred and fifty lymph nodes including 66 non-metastatic and 84 metastatic lymph nodes were matched using the radiological-pathological correlation. Metastatic node had a significantly greater λHU, n△HU and nIWR values than non-metastatic node in both arterial and venous phases (P < 0.01). The AUC, sensitivity and specificity were 0.80, 80.30% and 65.48% for λHU; 0.86, 69.70% and 95.24% for n△HU; 0.88, 71.21% and 95.24% for nIWR in the arterial phase. No significant difference was found in electron density and effective Z value for differentiation. Conclusion Dual-energy CT quantitative parameters may be helpful in diagnosing metastatic lymph nodes of CRC.

Nomogram Predicting the Likelihood of Parametrial Involvement in Early-Stage Cervical Cancer: Avoiding Unjustified Radical Hysterectomies

Background: We aimed to establish a tool predicting parametrial involvement (PI) in patients with early-stage cervical cancer and select a sub-group of patients who would most benefit from a less radical surgery. Methods: We retrospectively reviewed patients from two prospective multicentric databases—SENTICOL I and II—from 2005 to 2012. Patients with early-stage cervical cancer (FIGO 2018 IA with lympho-vascular involvement to IIA1), undergoing radical surgery (hysterectomy or trachelectomy) with bilateral sentinel lymph node (SLN) mapping with no metastatic node or PI on pre-operative imaging, were included. Results: In total, 5.2% patients (11/211) presented a histologic PI. After univariate analysis, SLN status, lympho-vascular space invasion, deep stromal invasion and tumor size were significantly associated with PI and were included in our nomogram. Our predictive model had an AUC of 0.92 (IC95% = 0.86–0.98) and presented a good calibration. A low risk group, defined according to the optimal sensitivity and specificity, presented a predicted probability of PI of 2%. Conclusion: Patients could benefit from a two-step approach. Final surgery (i.e. radical surgery and/or lymphadenectomy) would depend on the SLN status and the probability PI calculated after an initial conization with bilateral SLN mapping.

SAT-461 NIFTP: A Painstaking Diagnosis Through the Pathologist’s Eyes

Non-invasive encapsulated follicular variant of papillary thyroid cancer (EFVPTC) was recently reclassified as non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFT-P).1 In 2018, revised and stricter criteria were proposed for a lesion to qualify as NIFT-P including no well-formed papilla or BRAF-V600E mutation.2 We are presenting an interesting case to highlight the importance of scrutinizing pathology slides to diagnose NIFTP with these more strict criteria. 35-year-old female from Puerto-Rico was diagnosed with Graves’ disease. After 2 years of methimazole treatment, total thyroidectomy was planned for definitive treatment of Graves’ disease. During the work up, she was noted to have a cystic nodule in isthmus, a 1.1 cm hypoechoic nodule in left mid-lobe and a 1.1 cm isoechoic rounded mass in left level III neck, which was initially thought to be a lateral aberrant thyroid remnant. Her thyroid uptake scan was consistent with a multinodular goiter with no uptake in the extrathyroidal mass. The mass was biopsied and showed Atypia of Undetermined Significance (AUS) Bethesda III with washout positive for thyroglobulin (Tg). Total thyroidectomy with bilateral central and left lateral neck dissection was performed. The pathology showed an intrathyroidal 1.2 cm EFVPTC with predominant follicular features and &lt;1% papillae, without tumor capsular invasion. The initial diagnosis was NIFT-P with a background of chronic thyroiditis. However, on pathology, the level III neck mass was a 2 cm metastatic node with classical PTC. ThyroSeq mutational analysis of tissue blocks for both the thyroid nodule and lymph node were positive for NCOA4-RET (RET-PTC3) gene fusion, a BRAF-V600E-like mutation found in classical PTC. On review of her pathology, the thyroid lesion was noted to have more than one papilla, though &lt;1% papillae and was &gt;30% solid, hence not qualifying as NIFT-P and her histological diagnosis was changed to EFVPTC. She was staged as AJCC 8th edition stage 1 with intermediate ATA risk for which she received adjuvant therapy of 101 mCi 131I. Although classification into NIFT-P has been shown to reduce overtreatment of low risk encapsulated PTC, pathology slides should be closely scrutinized to ensure fulfillment of all criteria in order for a lesion to qualify as NIFT-P. This will minimize failure to recognize PTCs, that would warrant closer follow up and surveillance for recurrence. 1. Rossi, Esther D, et al. Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features: Update and Diagnostic Considerations—a Review. Endocrine Pathology 30.2 (2019) 2. Nikiforov, Yuri E et al. Change in Diagnostic Criteria for Noninvasive Follicular Thyroid Neoplasm With Papillary-like Nuclear Features. JAMA oncology vol. 4,8 (2018)

Combined Analysis of Intragastric Malignant Exfoliation and Ca 72.4 Concentration in Stomach Adenocarcinoma: The “GL1 Ca 72.4” Parameter

<b><i>Introduction/Objective:</i></b> Differently from other digestive malignancies, gastric cancer (GC) pathobiology is still little known and understood. Recently, cytopathology and molecular biology on gastric juice/gastric lavage (GJ/GL) of GC patients have provided novel and interesting results in terms of screening, diagnosis, prognosis, and therapy. However, entertaining cytologic examination and molecular test as a unified solo-run test is previously unreported. Our aim was to assess the new parameter “GL Ca 72.4” for GC patients. <b><i>Methods:</i></b> Between April 2012 and July 2013, GJ/GL obtained from 37 surgical GC patients were tested for the presence/absence (GL1/GL0) of exfoliated malignant cells along with the intragastric concentration of Ca 72.4 (normal value &#x3c;6.49 ng/mL: Ca 72.4n; elevated level ≥6.49 ng/mL: Ca 72.4+). <b><i>Results:</i></b> At a median follow-up of 79.3 months, all the GC alive patients were “GL0 Ca 72.4n.” The “GL1 Ca 72.4+” parameter, in comparison with GL0 Ca 72.4n, strongly correlated with deeper tumor invasion (<i>p</i> = 0.027), severe nodal metastasis (<i>p</i> = 0.012), worst metastatic node ratio (<i>p</i> = 0.041), higher number of metastatic lymph nodes (30 vs. 20 nodes, <i>p</i> = 0.014), angiolymphatic invasion (<i>p</i> = 0.044), advanced stage (<i>p</i> = 0.034), and adjuvant therapy (<i>p</i> = 0.044). The Kaplan-Meier model showed that GL1 Ca 72.4+ subjects had shorter overall survival (OS) than GL0 Ca 72.4n cases (9.7 vs. 43.2 months, respectively, <i>p</i> = 0.042). At univariate analysis, the GL1 Ca 72.4+ parameter resulted a significant prognostic factor for OS (<i>p</i> = 0.023). <b><i>Conclusions:</i></b> The combined cyto-molecular parameter “GL1 Ca 72.4+” appears to be a strong indicator of aggressive tumor behavior and a significant prognostic factor of poor survival for GC patients.

Role of EUS-FNA for gallbladder mass lesions with biliary obstruction: a large single-center experience

Background and study aims Although endoscopic ultrasound (EUS)-guided fine-needle aspiration (EUS-FNA) is an established modality for pathological sampling of pancreatic and biliary lesions, limited data are available on the diagnostic value of EUS-FNA for evaluation of gallbladder mass lesions, a common cause of obstructive jaundice. We aimed to evaluate the usefulness of EUS-FNA for diagnosis of gallbladder mass lesions presenting with biliary obstruction. Patients and methods This study was a retrospective analysis of data from patients who had undergone EUS-FNA for gallbladder mass lesions. FNA was performed on either a gallbladder mass, metastatic node or liver lesions. Outcome measures were diagnostic yield of EUS FNA and adverse events. Results From April 2011 to August 2018, 101 patients with gallbladder mass lesions with biliary obstruction underwent EUS-FNA. The final diagnosis was malignancy in 98, benign disease in one, and two patients were lost to follow-up. EUS-FNA confirmed the diagnosis in 89 of 98 patients with malignancy (sensitivity 90.81 %); was false negative in nine of 98 cases with malignancy; and was truly negative in the solitary patient with benign disease (specificity 100 %). Positive predictive value, negative predictive value (NPV), and accuracy were 100 %, 10 %, and 90.90 %, respectively. Two patients had self-limiting pain. Conclusion EUS-FNA is a sensitive tool for evaluation of gallbladder mass lesions presenting with obstructive jaundice. However, because of low NPV, lesions in which FNA is negative should be further evaluated.