Frequency and intensity of [18F]-PSMA-1007 uptake after COVID-19 vaccination in clinical PET

Objectives: To assess the frequency and intensity of [18F]-PSMA-1007 axillary uptake in lymph nodes ipsilateral to COVID-19 vaccination with BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) in patients with prostate cancer referred for oncological [18F]-PSMA PET/CT or PET/MR imaging. Methods: One hundred twenty six patients undergoing [18F]-PSMA PET/CT or PET/MR imaging were retrospectively included. [18F]-PSMA activity (SUVmax) of ipsilateral axillary lymph nodes was measured and compared with the non-vaccinated contralateral side-and with a non-vaccinated negative control group. [18F]-PSMA active lymph node metastases were measured to serve as quantitative reference. Results: There was a significant difference in SUVmax in ipsilateral and compared to contralateral axillary lymph nodes in the vaccination group (n = 63, p < 0.001) and no such difference in the non-vaccinated control group (n = 63, p = 0.379). Vaccinated patients showed mildly increased axillary lymph node [18F]-PSMA uptake as compared to non-vaccinated patients (p = 0.03). [18F]-PSMA activity of of lymph node metastases was significantly higher (p < 0.001) compared to axillary lymph nodes of vaccinated patients. Conclusions: Our data suggest mildly increased [18F]-PSMA uptake after COVID-19 vaccination in ipsilateral axillary lymph nodes. However, given the significantly higher [18F]-PSMA uptake of prostatic lymph node metastases compared to “reactive” nodes after COVID-19 vaccination, no therapeutic and diagnostic dilemma is to be expected. Advances in knowledge: No specific preparations or precautions (e.g., adaption of vaccination scheduling) need to be undertaken in patients undergoing [18F]-PSMA PET imaging after COVID-19 vaccination.

Predicting papillary thyroid carcinoma cervical lymph node metastases: an algorithm using the American College of Radiology Thyroid Imaging, Reporting and Data System

Background It is important to predict lymph node metastasis (LNM) in papillary thyroid carcinoma (PTC) preoperatively; however, the relationship between the American College of Radiology Thyroid Imaging, Reporting and Data System (ACR TI-RADS) score and cervical LNM remains unclear. Purpose To evaluate the association between the ACR TI-RADS score and cervical LNM in patients with PTC. Material and Methods This retrospective study consisted of 474 patients with 548 PTCs. Cervical LNM including central LNM (CLNM) and lateral LNM (LLNM) were confirmed by pathology. Univariate and multivariate analyses were performed to investigate the risk factors of CLNM and LLNM. Results Multivariate logistic regression analyses indicated that younger age and multifocality were risk factors for CLNM in PTCs with TR5. In addition, younger age, larger tumor size, and Hashimoto’s thyroiditis (HT) were risk factors for LLNM in PTCs ≥ 10 mm with TR5. In PTCs with TR4, ACR TI-RADS scores 5–6 conferred risks for LNM. In PTCs ≥ 10 mm with TR5, ACR TI-RADS scores ≥9 were risk factors for LLNM. Conclusion A higher ACR TI-RADS score is a predictor for cervical LNM in PTCs with TR4 and PTCs ≥ 10 mm with TR5.

The Diagnostic Accuracy of One-Step Nucleic Acid Amplification for Lymph Node Metastases of Papillary Thyroid Carcinoma： A Systematic Review and Meta-Analysis

BackgroundOne-step nucleic acid amplification (OSNA) analysis is a molecular diagnostic technique for lymph node metastases (LNMs) by quantifying cytokeratin 19(CK 19) mRNA. We aim to evaluate the intraoperative diagnostic accuracy of OSNA assay for LNMs of papillary thyroid carcinoma (PTC).MethodsPubMed, Embase, Cochrane Library, and Web of Science databases were searched to retrieve related literature. A meta-analysis was performed using STATA11.0, Meta-Disc 1.4 and RevMan 5.3.ResultsThis meta-analysis included six studies involving 987 lymph nodes from 194 patients. The pooled sensitivity, specificity, and area under the summary receiver-operating characteristic curve (AUC) of OSNA for detecting LNM were 0.88, 0.90, and 0.95, respectively.ConclusionOSNA assay is an accurate molecular diagnosis for intraoperative detection of lymph node metastasis in PTC.

Pancreatic fibrosis, acinar atrophy and chronic inflammation in surgical specimens associated with survival in patients with resectable pancreatic ductal adenocarcinoma

Background Pancreatic ductal adenocarcinoma (PDAC), one of the most lethal malignancies, is increasing in incidence. However, the stromal reaction pathophysiology and its role in PDAC development remain unknown. We, therefore, investigated the potential role of histological chronic pancreatitis findings and chronic inflammation on surgical PDAC specimens and disease-specific survival (DSS). Methods Between 2000 and 2016, we retrospectively enrolled 236 PDAC patients treated with curative-intent pancreatic surgery at Helsinki University Hospital. All pancreatic transection margin slides were re-reviewed and histological findings were evaluated applying international guidelines. Results DSS among patients with no fibrosis, acinar atrophy or chronic inflammation identified on pathology slides was significantly better than DSS among patients with fibrosis, acinar atrophy and chronic inflammation [median survival: 41.8 months, 95% confidence interval (CI) 26.0–57.6 vs. 20.6 months, 95% CI 10.3–30.9; log-rank test p = 0.001]. Multivariate analysis revealed that Ca 19–9 > 37 kU/l [hazard ratio (HR) 1.48, 95% CI 1.02–2.16], lymph node metastases N1–2 (HR 1.71, 95% CI 1.16–2.52), tumor size > 30 mm (HR 1.47, 95% CI 1.04–2.08), the combined effect of fibrosis and acinar atrophy (HR 1.91, 95% CI 1.27–2.88) and the combined effect of fibrosis, acinar atrophy and chronic inflammation (HR 1.63, 95% CI 1.03–2.58) independently served as unfavorable prognostic factors for DSS. However, we observed no significant associations between tumor size (> 30 mm) and the degree of perilobular fibrosis (p = 0.655), intralobular fibrosis (p = 0.587), acinar atrophy (p = 0.584) or chronic inflammation (p = 0.453). Conclusions Our results indicate that the pancreatic stroma is associated with PDAC patients’ DSS. Additionally, the more severe the fibrosis, acinar atrophy and chronic inflammation, the worse the impact on DSS, thereby warranting further studies investigating stroma-targeted therapies.

Surgical Treatment of Low-Lying Rectal Cancer: Updates

Despite innovative advancements, distally located rectal cancer remains a critical disease of challenging management. The crucial location of the tumor predisposes it to a circumferential resection margin (CRM) that tends to involve the anal sphincter complex and surrounding organs, with a high incidence of delayed anastomotic complications and the risk of the pelvic sidewall or rarely inguinal lymph node metastases. In this regard, colorectal surgeons should be aware of other issues beyond total mesorectal excision (TME) performance. For decades, the concept of extralevator abdominoperineal resection to avoid compromised CRM has been introduced. However, the complexity of deep pelvic dissection with poor visualization in low-lying rectal cancer has led to transanal TME. In contrast, neoadjuvant chemoradiotherapy (NCRT) has allowed for the execution of more sphincter-saving procedures without oncologic compromise. Significant tumor regression after NCRT and complete pathologic response also permit applying the watch-and-wait protocol in some cases, now with more solid evidence. This review article will introduce the current surgical treatment options, their indication and technical details, and recent oncologic and functional outcomes. Lastly, the novel characteristics of distal rectal cancer, such as pelvic sidewall and inguinal lymph node metastases, will be discussed along with its tailored and individualized treatment approach.

Rethinking the TNM Classification Regarding Direct Lymph Node Invasion in Pancreatic Ductal Adenocarcinoma

Mechanisms of lymph node invasion seem to play a prognostic role in pancreatic ductal adenocarcinoma (PDAC) after resection. However, the 8th edition of the TNM classification of the American Joint Committee on Cancer (AJCC) does not consider this. The aim of this study was to analyse the prognostic role of different mechanisms of lymph node invasion on PDAC. One hundred and twenty-two patients with resected PDAC were examined. We distinguished three groups: direct (per continuitatem, Nc) from the main tumour, metastasis (Nm) without any contact to the main tumour, and a mixed mechanism (Ncm). Afterwards, the prognostic power of the different groups was analysed concerning overall survival (OS). In total, 20 patients displayed direct lymph node invasion (Nc = 16.4%), 44 were classed as Nm (36.1%), and 21 were classed as Ncm (17.2%). The difference in OS was not statistically significant between N0 (no lymph node metastasis, n = 37) and Nc (p = 0.134), while Nm had worse OS than N0 (p < 0.001). Direct invasion alone had no statistically significant effect on OS (p = 0.885). Redefining the N0 stage by including Nc patients showed a more precise OS prediction among N stages (p = 0.001 vs. p = 0.002). Nc was more similar to N0 than to Nm; hence, we suggest a rethinking of TNM classification based on the mechanisms of lymph node metastases in PDAC. Overall, this novel classification is more precise.

Correlation of Somatostatin Receptor 1–5 Expression, [68Ga]Ga-DOTANOC, [18F]F-FDG PET/CT and Clinical Outcome in a Prospective Cohort of Pancreatic Neuroendocrine Neoplasms

Purpose: The aim of this study was to correlate immunohistochemical (IHC) tissue levels of SSTR1-5 with the receptor density generated from [68Ga]Ga-DOTANOC uptake in a prospective series of NF-PNENs. Methods: Twenty-one patients with a total of thirty-five NF-PNEN-lesions and twenty-one histologically confirmed lymph node metastases (LN+) were included in this prospective study. Twenty patients were operated on, and one underwent endoscopic ultrasonography and core-needle biopsy. PET/CT with both [68Ga]Ga-DOTANOC and [18F]F-FDG was performed on all patients. All histological samples were re-classified and IHC-stained with monoclonal SSTR1-5 antibodies and Ki-67 and correlated with [68Ga]Ga-DOTANOC and [18F]F-FDG PET/CT. Results: Expression of SSTR1-5 was detected in 74%, 91%, 80%, 14%, and 77% of NF-PNENs. There was a concordance of SSTR2 IHC with positive/negative [68Ga]Ga-DOTANOC finding (Spearman’s rho 0.382, p = 0.043). All [68Ga]Ga-DOTANOC-avid tumors expressed SSTR2 or SSTR3 or SSTR5. Expression of SSTR5 was higher in tumors with a low Ki-67 proliferation index (PI) (−0.353, 95% CI −0.654–0.039, p = 0.038). The mean Ki-67 PI for SSTR5 positive tumors was 2.44 (SD 2.56, CI 1.0–3.0) and 6.38 (SD 7.25, CI 2.25–8.75) for negative tumors. Conclusion: SSTR2 was the only SSTR subtype to correlate with [68Ga]Ga-DOTANOC PET/CT. Our prospective study confirms SSTR2 to be of the highest impact for SST PET/CT signal.

[18F]FDG-PET accurately identifies pathological response early upon neoadjuvant immune checkpoint blockade in head and neck squamous cell carcinoma

Purpose To investigate the utility of [18F]FDG-PET as an imaging biomarker for pathological response early upon neoadjuvant immune checkpoint blockade (ICB) in patients with head and neck squamous cell carcinoma (HNSCC) before surgery. Methods In the IMCISION trial (NCT03003637), 32 patients with stage II‒IVb HNSCC were treated with neoadjuvant nivolumab with (n = 26) or without (n = 6) ipilimumab (weeks 1 and 3) before surgery (week 5). [18F]FDG-PET/CT scans were acquired at baseline and shortly before surgery in 21 patients. Images were analysed for SUVmax, SUVmean, metabolic tumour volume (MTV), and total lesion glycolysis (TLG). Major and partial pathological responses (MPR and PPR, respectively) to immunotherapy were identified based on the residual viable tumour in the resected primary tumour specimen (≤ 10% and 11–50%, respectively). Pathological response in lymph node metastases was assessed separately. Response for the 2 [18F]FDG-PET-analysable patients who did not undergo surgery was determined clinically and per MR-RECIST v.1.1. A patient with a primary tumour MPR, PPR, or primary tumour MR-RECIST-based response upon immunotherapy was called a responder. Results Median ΔSUVmax, ΔSUVmean, ΔMTV, and ΔTLG decreased in the 8 responders and were significantly lower compared to the 13 non-responders (P = 0.05, P = 0.002, P < 0.001, and P < 0.001). A ΔMTV or ΔTLG of at least − 12.5% detected a primary tumour response with 95% accuracy, compared to 86% for the EORTC criteria. None of the patients with a ΔTLG of − 12.5% or more at the primary tumour site developed a relapse (median FU 23.0 months since surgery). Lymph node metastases with a PPR or MPR (5 metastases in 3 patients) showed a significant decrease in SUVmax (median − 3.1, P = 0.04). However, a SUVmax increase (median + 2.1) was observed in 27 lymph nodes (in 11 patients), while only 13 lymph nodes (48%) contained metastases in the corresponding neck dissection specimen. Conclusions Primary tumour response assessment using [18F]FDG-PET-based ΔMTV and ΔTLG accurately identifies pathological responses early upon neoadjuvant ICB in HNSCC, outperforming the EORTC criteria, although pseudoprogression is seen in neck lymph nodes. [18F]FDG-PET could, upon validation, select HNSCC patients for response-driven treatment adaptation in future trials. Trial registration https://www.clinicaltrials.gov/, NCT03003637, December 28, 2016.

Report on Unusual Sites of Lymph Node Metastases in Nasopharyngeal Carcinoma

Nasopharyngeal carcinoma (NPC) is amongst the most common malignancies of head and neck cancers. Most patients are admitted to the hospital with advanced disease. NPC has a tendency toward early metastatic spread to cervical lymph nodes, and levels II and III are most commonly involved. A few reports have indicated specific metastatic sites of nasopharyngeal cancer, including lymph node metastasis and distant metastasis. Evidence of histopathology and immunohistochemistry is required to prove NPC origin. In many cases, surgery can be performed to obtain accurate evidence of the pathology. However, surgery can also affect the overall treatment plan and strategy for NPC and should be considered in the specific circumstances of the disease. Multidisciplinary consultation is required for these uncommonly specific metastases. Paying attention to the specific lymph node metastasis sites of NPC plays an important role in accurately diagnosing the stage, thereby giving an appropriate treatment strategy. It is also important in determining radiotherapy volumes because radiotherapy is the standard therapy for this disease. Herein, we are reporting 2 cases of NPC with clinical metastasis to unusual lymph node sites such as the parotid salivary gland and the cheek. Histological analyses from the resected specimens confirmed its nasopharyngeal origin. Lymph node metastases in the parotid gland and the cheek are unusual. In diagnosis and follow-up, it is necessary to evaluate carefully to make an accurate diagnosis and appropriate treatment plans for patients as well as early detect recurrent metastases at uncommon sites of lymph nodes.