Occult Metastases Research Articles

Metastasis of tongue cancer locatedunilaterally, not crossing the midline,to the lymph nodes of the neck.

<br><b>Introduction:</b> In recent years, there has been a steady increase in the incidence of tongue cancer. Rapid asymptomatic growth, early metastases, and crossing lymphatic drainage of the tongue reduce the chances of successful therapy. The presence of metastases in cervical lymph nodes is also an important prognostic factor.</br> <br><b>Aim:</b> The aim of the study is a retrospective analysis of the incidence of unilateral and bilateral metastases within the cervical lymphatic system in patients with unilateral tongue cancer that does not cross the midline.</br> <br><b>Materials and methods:</b> A retrospective study of a group of patients hospitalized and treated for malignant tongue cancers at the Clinical Ward of Cranio-Maxillo-Facial Surgery of the Department of Otolaryngology and Laryngological Oncology of the Military Institute of Medicine-National Research Institute in Warsaw in 2012-2023. As many as 106 patients treated for unilateral tongue cancer that has not crossed the midline were selected, who also underwent unilateral or bilateral cervical lymphadenectomy, apart from primary tumor resection and reconstruction. The analysis was based on the medical records of the patients, results of imaging and histopathological examinations, and surgical procedure protocols.</br> <br><b>Results:</b> In a group of 106 patients with unilateral tongue cancer, in whom the cancer did not cross the midline, 47 patients underwent unilateral lymphadenectomy, of which 16 had lymph node metastases. Bilateral lymph node removal was performed in 59 patients. In 26 cases metastases were detected only in ipsilateral lymph nodes, and in 13 cases metastases were found in contralateral lymph nodes. Among 106 patients, occult metastases were detected in 21 patients.</br> <br><b>Conclusions:</b> Due to the crossing of the lymphatic drainage of the tongue, which allows for the possibility of contralateral metastases, and the impact of the operation on oncological efficacy, it is reasonable to perform bilateral cervical lymphadenectomy.</br&gt.

Primary Neuroendocrine Tumor in Type-1C Choledochal Cyst

Cholangiocarcinoma is the most common biliary tumor and a dreaded complication of choledochal cyst. However, the development of neuroendocrine tumor (NET) in choledochal cyst is very rare due to the paucity of Kulchitsky cells. Here, we are presenting a case report on primary NET in choledochal cyst. To date, only four case reports have been published globally and all of them were diagnosed postsurgically; this is the first case diagnosed prior. A 45-year-old female presented with abdominal pain. Imaging showed dilated common hepatic duct and proximal common bile duct with soft-tissue mass lesion in the lateral wall, infiltrating the liver with liver metastasis (suspected as cholangiocarcinoma). As the patient was inoperable, palliative care was planned. To have tissue diagnosis, we proceeded with endoscopic retrograde cholangiopancreatography and brush cytology, but no malignant cells were detected. Image-guided biopsy was done, and surprisingly, the report came to be NET. To rule out occult metastasis elsewhere, positron emission tomography–computed tomography (DOTANOC) scan was done, which was suggestive of a primary bile duct growth with multiple liver metastases. Because of slow growth, nonfunctional nature, and clinical and radiological resemblance with cholangiocarcinoma, biliary tract NETs are very difficult to diagnose preoperatively.

Clinical value of dual-energy CT for predicting occult metastasis in central neck lymph nodes of papillary thyroid carcinoma.

To predict the probability of occult lymph node metastasis (OLNM) in the central cervical by analyzing the dual-energy computed tomography (DECT) parameters derived from papillary thyroid carcinoma (PTC). Data were retrospectively collected from patients with pathologically confirmed PTC who underwent arterial and venous phases of enhanced DECT with concurrent central neck lymph node dissection (CLND). Three clinical features, three shape-related features, and twenty-six DECT-derived parameters were measured. The univariate and multivariate analyses were applied to select the relevant parameters and develop the nomogram. A total 140 cases with negative diagnosis of cervical central lymph node metastases by preoperative evaluation were included, among which 88 patients with metastasis (OLNM +) and 52 patients without metastasis (OLNM -) were finally confirmed by pathology.(1) Anteroposterior/transverse diameter ratio (A/T) derived from the PTC focus had significant difference between the OLNM + and OLNM - groups (p < 0.05). (2) In the arterial phase, iodine concentration (ICarterial), normalized iodine concentration (NICarterial), effective atomic number (Zeff-arterial), electron density (EDarterial), and slope of energy curve (karterial) from PTC focus showed significant difference (all p < 0.05) between the two groups. In the venous phase, only the CT value under the 40keV (HU40keVvenous) had differences (p < 0.05). (3) The nomogram was produced to predict the probability of OLNM, and the AUC, sensitivity, and specificity in the training and test cohort were 0.830, 75.0%, 76.9%, and 0.829, 65.9%, 84.6%, respectively. DECT parameters combined with shape-related feature derived from PTC might be used as predictors of OLNM in the central neck. Preoperative imaging evaluation combining shape-related features and dual-energy CT parameters could serve as a reference to discern occult lymph node metastasis in central neck during the surgically planning of papillary thyroid carcinoma. • Papillary thyroid carcinoma (PTC) patients may have occult lymph node metastasis (OLNM) in the central neck, which is extremely difficult to find by preoperative imaging examination. • Dual-energy CT quantitative evaluation has higher accuracy than conventional CT and can predicting OLNM in the central neck of PTC. • Dual-energy CT quantitative parameters and morphology of PTC can serve as a useful tool in predicting OLNM in the central neck, and as a guide for personalized treatment.

Hot dots – which nodes should be removed in sentinel lymph node biopsy for melanoma?

Background Sentinel lymph node biopsy (SLNB) is a critical staging tool for melanoma patients. The optimal number of lymph nodes removed in SLNB remains unclear. In this study, we retrospectively analysed and tested different criteria for selecting sentinel lymph nodes (SLNs) by radiotracer uptake and blue dye, and their impact on nodal staging. We also evaluated the association between SLN tumour burden and radiotracer uptake. Methods The study population consisted of melanoma patients undergoing SLNB. During the operation all radioactive and blue nodes were removed and sent for histopathological analysis. The ex vivo radioactive count and presence of blue dye of each node were recorded, and these were correlated with presence and size of metastasis in each SLN. Results Altogether 175 patients with clinically occult metastasis presented with one or more positive, i.e. metastatic, SLNs. The mean number of lymph nodes removed was 4.5, and the mean number of positive lymph nodes was 1.5 per patient. The most radioactive or hottest node was negative in 38 patients (22%). By removing the hottest node and all nodes with radioactivity >10% of the hottest node, 97% of patients would have been staged correctly. In five patients, metastasis was found solely in a SLN with radioactivity <10% of the hottest node. Of all 267 positive nodes removed, 125 (47%) contained blue dye. Patients with a negative hottest node were associated with lower SLN tumour burden. Conclusions By removing the hottest node and all nodes with radioactivity >10% of the hottest node, 97% of patients with SLN metastases are correctly staged with or without using blue dye.

The current state and future of neoadjuvants in resectable melanoma: Review of phase II/III studies conducted between 2018-2022.

e21568 Background: Adjuvant therapy with single agent anti-PD1 and BRAF/MEK-inhibitors (BRAF/MEKi) is approved for patients diagnosed with high-risk stage III melanoma. The goal of adjuvant therapy is to prevent the growth of the occult metastasis to distant organs. The premise of neoadjuvant therapy in clinical stage III melanoma is to allow for a better antigen exposure when checkpoint inhibitors are administered. We aimed to get an overview of the current state of neoadjuvant therapy in resectable melanoma. Methods: A systematic literature search was conducted in November 2022, using PubMed, American Society of Clinical Oncology (ASCO) Journal of Clinical Oncology and European Society for Medical Oncology (ESMO) abstract databases. Eligible studies included Phase 2 and 3 randomized controlled trials (RCT), single-arm trials, pooled analyses, and planned future trials published between 2018-2022 looking at the efficacy of neoadjuvants in resectable melanoma. Two individuals (CL and MM) screened all the studies, and 3 individuals (CM, MM, MW) went over the list of Abstracts. Primary outcomes and secondary outcomes, as well as median duration of follow up and Grade 3 or above adverse effects (AEs) were recorded. Abstracts with more recent findings or final publications were excluded in the final analysis. Results: A total of 14 published studies (4 RTCs, 5 single-arm, 2 OpACIN-neo and 3 related sub-analysis studies) and 16 abstracts (5 ESMO, 11 ASCO) were identified, representing 34 unique Neoadjuvant arms and a total of 1,496 patients. Thirteen of 27 trials making 71% of patients (n = 1061) tested immune checkpoint inhibitors (ICIs). Four of 27 trials of total n = 112 tested BRAF/MEKi. All ongoing or future studies (7 trials) tested combination of ICI with BRAF/MEKi or other molecules such as MDM2 inhibitors, interferon-α, or oncolytic viruses. Most of studies (54% of ICI studies, 50% of BRAF/MEK inhibitor trials, and 80% of other studies) used pathological response as their primary outcome. Other primary end points included event-free survival (EFS) and relapse-free survival (RFS), and 13/14 published studies and 13/16 abstracts met the primary end point. A pooled analysis of complete pathologic response (pCR) revealed an estimate of 38.3% ± 19.7 (mean ± SD) from 16 unique ICI neoadjuvant arms, 51.9% ± 5.3 for BRAF/MEKi (from 3 data points), and 21.0% ± 7.2 for other agents/combinations (from 3 data points). Rate of ≥ Grade 3 AEs was 28.7% ± 31.0 (from 11 data points) for studies testing ICI, 32.5% ± 14.1 (from 6 data points) for BRAF/MEKi, and 23.6% ± 20.2 (from 3 data points) from studies testing other agents/combinations. Conclusions: Recent studies have shown that neoadjuvant in resectable melanoma can offer increased therapeutic efficacy. While past studies have focused on PD-1 and CTLA-4 inhibitors, ongoing and future studies are beginning to test newer agents and novel molecular targets.

Discordance Between Conventional and Detailed Lymph Node Analysis in Resected, Node-negative Pancreatic or Ampullary Adenocarcinomas and Association With Adverse Survival Outcomes: A Single-institution Analysis.

To assess the frequency of occult metastases (OM) in patients with resected pancreatic ductal adenocarcinoma (PDAC) or ampullary adenocarcinoma (AA) discovered on detailed pathologic examination on lymph nodes (LNs) previously considered negative by conventional analysis and to examine the association between OM and overall survival (OS). Poor prognosis of patients with no pathologic evidence of LN metastases may be due to OM that is not detected on conventional LN analysis. Patients with LN-negative resected PDAC or AA (2010-2020) were identified from our institutional database. Original hematoxylin and eosin ( H and E ) slides were reanalyzed. In addition, selected LN were analyzed by H and E (3 sections/LN) and pan-cytokeratin (AE1-AE3/PCK26) immunohistochemistry. A total of 598 LNs from 74 LN-negative patients were reexamined. Nineteen patients (25.7%) had OM; 9 (47.4%) were found with immunohistochemistry but not on H and E . The number of positive LNs ranged from 1 to 3. No clinicodemographic, pathologic, or treatment-related factors were associated with OM. On conventional LN analysis, 3/19 patients (15.8%) had stage IA, 9/34 (26.5%) had stage IB, and 7/19 (36.8%) had stage IIA. On detailed LN analysis, 11/19 patients (57.9%) were upstaged to IIB, whereas 8/19 (42.1%) had isolated tumor cells only (N0i+). OM was associated with shorter OS (median OS: 22.3 vs 50.5 months; hazard ratio=3.95, 95% CI: 1.58-9.86). There is a 26% discordance rate between conventional and detailed LN pathologic analysis in resected PDAC and AA. The presence of OM is associated with shorter OS.

Rim Enhancement and Peripancreatic Fat Stranding in Preoperative MDCT as Predictors for Occult Metastasis in PDAC Patients

To identify the radiological features and clinical biomarkers that could predict the occult metastasis (OM) of pancreatic ductal adenocarcinoma (PDAC). This retrospective study included PDAC patients who were radiologically diagnosed resectable (R) or borderline resectable (BR) and underwent surgical exploration from January 2018 to December 2021. Depending on whether distant metastases were found during the exploration, patients were divided into OM and non-OM groups. Univariate and multivariable logistic regression analyses were performed to determine the radiological and clinical predictive factors for occult metastasis. Model performance was determined by discrimination and calibration. A total of 502 patients (median age, 64 years; interquartile range, 57-70 years; 294 men) were enrolled, among which 68 (13.5%) patients were found with distant metastases, with 45 liver-only, 19 peritoneal-only, four patients had both liver and peritoneal metastases. Rim enhancement and peripancreatic fat stranding were more frequent in the OM group than in the non-OM group. Tumor size (p = 0.028), tumor resectability (p = 0.031), rim enhancement (p < 0.001), peripancreatic fat stranding (p < 0.001) and level of CA125 (p=0.021) were independent predictors of occult metastasis according to the multivariable analyses, and the areas under the curve (AUCs) of these characteristics were 0.703, 0.594, 0.638, 0.655, 0.631, respectively. The combined model showed the highest AUC of 0.823. Rim enhancement, peripancreatic fat stranding, tumor size, tumor resectability and level of CA125 are risk factors for OM of PDAC. The combined model of radiological and clinical features may help the preoperative prediction of OM in PDAC.

MP40-11 CONTRIBUTION OF GLEASON PATTERN 4 PROSTATE CANCER TISSUE TO PRE-OPERATIVE PSA VALUES IN INTERMEDIATE RISK PROSTATE CANCER: RESULTS FROM 4 860 RP SPECIMENS

You have accessJournal of UrologyCME1 Apr 2023MP40-11 CONTRIBUTION OF GLEASON PATTERN 4 PROSTATE CANCER TISSUE TO PRE-OPERATIVE PSA VALUES IN INTERMEDIATE RISK PROSTATE CANCER: RESULTS FROM 4 860 RP SPECIMENS Fabian Falkenbach, Lukas Hohenhorst, Zhe Tian, Mykyta Kachanov, Tobias Maurer, Sophie Knipper, Markus Graefen, and Lars Budäus Fabian FalkenbachFabian Falkenbach More articles by this author , Lukas HohenhorstLukas Hohenhorst More articles by this author , Zhe TianZhe Tian More articles by this author , Mykyta KachanovMykyta Kachanov More articles by this author , Tobias MaurerTobias Maurer More articles by this author , Sophie KnipperSophie Knipper More articles by this author , Markus GraefenMarkus Graefen More articles by this author , and Lars BudäusLars Budäus More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003278.11AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Despite advances in imaging and genetic testing, blood PSA remains the cornerstone of prostate cancer (PCa) diagnosis and risk stratification. Especially in the management of intermediate-risk PCa, the PSA value has strong implications for clinical decision-making. It is known, that within this group Gleason pattern (GP) 4 drives biological aggressiveness. Aim of our study was to assess the relationship between pre-operative blood PSA values and volume of GP 4 compared to GP 3 and benign tissue in Radical Prostatectomy (RP) specimens. METHODS: Overall, 4860 patients with localized pT2pN0cM0, intermediate risk PCa without tertiary GP were assessed. Individual GPs were quantified at the whole-mount section analysis of RP specimen. For analysis, patients with biochemical recurrence after RP and a pre-operative PSA >50 ng/ml were further excluded for avoiding contamination of the cohort by occult metastasis. Moreover, patients with prior / neoadjuvant treatment, a gland size <10 cc after TUR-P or gland size >150 cc (associated risk of chronic inflammation) were excluded. Multivariable linear regression analysis addressed the relationship between volume of tissue types and PSA values. RESULTS: Of 4860 patients, in 4390 (90%) a Gleason Score of 3+4 and in 470 (10%) a Gleason Score of 4+3 was present. Median age at RP was 63 years (IQR: 58-68 years), median PSA was 6.4ng/ml (IQR: 4.8-8.7ng/ml) and median prostate volume was 30cc (IQR: 23-40cc). PSA as well as PSA-Density were associated with the quantitative GP 4 fraction above 50% (p-value: <0.001). GP 4 tissue contributed to the pre-operative PSA by 0.37 ng/ml per cc, GP 3 and benign prostate tissue combined contributed by 0.062 ng/ml per cc (p-value: <0.001). There was no significant difference in PSA contribution between GP 3 and benign tissue. CONCLUSIONS: The highest contribution to PSA prior RP originates from GP 4 PCa tumor foci. PSA expression of GP 3 and benign tissue were not significantly different. This confirms the discussed potential indolent nature of GP 3 PCa. Within intermediate risk PCa, PSA is a strong surrogate parameter for the amount of GP 4 PCa tissue. Further confirmatory studies including e.g. imaging data are needed for excluding potential selection bias. Source of Funding: None. © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e549 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Fabian Falkenbach More articles by this author Lukas Hohenhorst More articles by this author Zhe Tian More articles by this author Mykyta Kachanov More articles by this author Tobias Maurer More articles by this author Sophie Knipper More articles by this author Markus Graefen More articles by this author Lars Budäus More articles by this author Expand All Advertisement PDF downloadLoading ...

MP32-03 INCIDENCE AND OUTCOMES OF OCCULT LYMPH NODE METASTASIS IN CLINICALLY CT2-4A NO BLADDER CANCER AT RADICAL CYSTECTOMY WITH OR WITHOUT NEOADJUVANT CHEMOTHERAPY

You have accessJournal of UrologyCME1 Apr 2023MP32-03 INCIDENCE AND OUTCOMES OF OCCULT LYMPH NODE METASTASIS IN CLINICALLY CT2-4A NO BLADDER CANCER AT RADICAL CYSTECTOMY WITH OR WITHOUT NEOADJUVANT CHEMOTHERAPY Mahmoud Laymon, Ahmed Elkarta, Amr Elsawy, Osama Ezzat, Ahmed Mosbah, and Hassan Abol-Enein Mahmoud LaymonMahmoud Laymon More articles by this author , Ahmed ElkartaAhmed Elkarta More articles by this author , Amr ElsawyAmr Elsawy More articles by this author , Osama EzzatOsama Ezzat More articles by this author , Ahmed MosbahAhmed Mosbah More articles by this author , and Hassan Abol-EneinHassan Abol-Enein More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003265.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Radical cystectomy with pelvic lymphadenectomy is the standard treatment of muscle invasive bladder cancer (BC). However, nearly 50% of patients experience tumor recurrence that can be attributed to presence of occult metastasis at the tie of surgery. One of the goals of neoadjuvant chemotherapy (NAC) is to eliminate micro-metastasis before surgery. We aim to compare nodal metastasis at a large cohort of cNoMo patients treated with cystectomy alone and NAC then cystectomy. METHODS: We reviewed the electronic files of 622 consecutive patients diagnosed with cT2-4a NoMo urothelial BC and treated with radical cystectomy between January2004 till December 2014. We also analyzed a recent prospective database of 46 cNoMo patients treated with Cisplatin based NAC then RC between January 2019 till August 2021. The primary end point was the incidence of occult LN metastasis among both groups. The secondary endpoint was to assess recurrence free survival (RFS) in both groups using Kaplan Meier method. RESULTS: Baseline clinical and histopathological characteristics of both groups are shown in Table (1). In the NAC group, 18 patients (39%) had no residual tumor (pTo). Overall, pathological evaluation showed that 140 (21%) of patients had nodal metastasis, eight patients (17.4%) of the NAC group vs 132 (21.2%) of the non-NAC group (p=0.7). Among the patients with cT2 disease, LN metastases were found in 21.5% (23/107) of cases, five patients in NAC (22.7%) group and 18 (21.2%) patients in non NAC group (p=0.8). Regarding, non NAC group, the estimated 1,3and 5 year RFS between pNO vs pN+ve was 90.2%,74.5 and 70.4% vs 83.7, 42.5% and 40% (p<0.0001), respectively. CONCLUSIONS: Presence of occult lymph node metastasis in cNo bladder cancer is not uncommon reaching 21% of cases. Even in clinically organ confined (cT2No) disease, pathologically confirmed nodal metastasis was found in 21.5% of cases. Occult lymph node metastasis was associated with worse RFS. Inspite of the down staging effect of NAC on the primary bladder tumor, nodal metastasis can still be found in 17.4% of patients. These findings should be considered during counselling patients for NAD or bladder sparing treatment. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e440 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Mahmoud Laymon More articles by this author Ahmed Elkarta More articles by this author Amr Elsawy More articles by this author Osama Ezzat More articles by this author Ahmed Mosbah More articles by this author Hassan Abol-Enein More articles by this author Expand All Advertisement PDF downloadLoading ...

Assessment of depth of invasion in oral squamous cell carcinoma of the tongue: a study protocol

Background:Oral Squamous Cell Carcinoma (OSCC) is the most common malignancy of oral cavity. It remains a leading cause of mortality and morbidity around the world. Overall OSCC represents more than 550,000 cases throughout the world yearly and the 6thleading cause of death. The mortality and rate of OSCC are higher in developing nations. About 25% patients with OSCC of tongue exist with occult metastasis at initial presentation. The utilization of TNM staging of OSCC to assess the clinical response to treatment and survival result is for many years. Prognosis of malignancy also depends on the histopathological grading of the OSCC. Histopathological assessment by measuring Depth of Invasion (DOI) enables us the insight about the extent of invasion by neoplastic cells. This observation will further be helpful for treatment management protocol particularly in OSCC of tongue. Hence, we aimed to assess the significance of DOI in the prognosis and clinicopathological features and survival of OSCC lesions in the current study.Methods:The surgically operated cases of OSCC of tongue from year 2009 to 2015 will be retrieved from the archival. Measurement of DOI will be carried out using Research microscope. The staging of the patients will be done according to the American Joint Committee of Cancer staging system. The present study will find DOI in tongue OSCC and its correlation with the clinicopathological features of OSCC of tongue and three years disease-specific survival.Conclusion:Measurement of the DOI ought to be included as a part of routine histological assessment. This likewise should be utilized for grading the tumor, which can further help in treatment management protocol.

Indications for elective neck dissection in cT1N0M0 oral cavity cancer according to the AJCC eight edition: A nationwide study

ObjectivesAccording to the NCCN guidelines, there is weak evidence to support the use of elective neck dissection (END) in early-stage oral cavity squamous cell carcinoma (OCSCC). We sought to examine the indications for END in patients with cT1N0M0 OCSCC defined according to the AJCC Staging Manual, Eight Edition. MethodsOf the 3886 patients diagnosed with cT1N0M0 included in the study, 2065 underwent END and 1821 neck observation. ResultsThe 5-year outcomes for patients who received END versus neck observation before and after propensity score matching (n = 1406 each) were as follows: neck control, 96 %/90 % (before matching), p < 0.0001; 96 %/90 % (after matching), p < 0.0001; disease-specific survival (DSS), 93 %/92 % (before matching), p = 0.0227; 93 %/92 % (after matching), p = 0.1436. Multivariable analyses revealed that neck observation, depth of invasion (DOI) > 2.5 mm, and poor differentiation were independent risk factors for 5-year outcomes. Upon the application of a scoring system ranging from 0 (no risk factor) to 3 (presence of the three risk factors), the following 5-year rates were observed: neck control, 98 %/95 %/84 %/85 %; DSS, 96 %/93 %/88 %/85 %; and overall survival, 90 %/86 %/79 %/59 %, respectively (all p < 0.0001). The survival outcomes of patients with scores of 0 and 1 were similar. The occult metastasis rates in the entire study cohort, DOI > 2.5 mm, and poor differentiation were 6.8 %/9.2 %/17.1 %, respectively. ConclusionBecause all patients who received neck observation had a score of 1 or higher, END should be performed when a DOI > 2.5 mm or poorly differentiated tumors are present. Under these circumstances, 48.6 % (1888/3886) of cT1N0M0 patients may avoid END without compromising oncological outcomes.

Merkel cell carcinoma: epidemiology, clinical features, diagnosis and treatment of a rare disease

Merkel cell carcinoma is a rare skin cancer with neuroendocrine differentiation. The risk factors include sun exposure, advanced age, immunosuppression (such as transplant recipients, patients with lymphoproliferative neoplasms, or patients with HIV), and Merkel cell polyomavirus infection. Clinically, Merkel cell carcinoma appears as a cutaneous or subcutaneous plaque or nodule, but this tumor diagnosis is rarely made clinically. Therefore, histopathology and immunohistochemistry are usually necessary. Primary tumors without evidence of metastases are treated with complete surgical excision and appropriate surgical margins. The presence of occult metastasis in a lymph node is frequent and a sentinel lymph node biopsy should be performed. Postoperative adjuvant radiotherapy increases local tumor control. Recently, agents that block the PD-1/PD-L1 pathway have shown objective and durable tumor regression in patients with advanced solid malignancies. The first anti-PD-L1 antibody used in patients with Merkel cell carcinoma was avelumab, but pembrolizumab and nivolumab have also shown efficacy. This article describes the current state of knowledge of the epidemiology, diagnosis, and staging of Merkel cell carcinoma, as well as new strategies for its systemic treatment.

Utility of Elective Neck Dissection in Clinically Node-Negative Parotid Malignancy.

We sought to investigate the utility of elective neck dissection (END) in clinically node-negative parotid malignancy through the evaluation of factors that are associated with receiving END and survival analysis of patients who received END. Retrospective cohort database study. The National Cancer Database (NCDB). The NCDB was used to extract patients with clinically node-negative parotid malignancy. END was defined as having 5or more lymph nodes examined pathologically, as previously defined in the literature. Univariate and multivariate analyses were used to compare predictors of receiving END, rates of occult metastasis, and survival. Of the 9405 included patients, 3396 (36.1%) underwent an END. END was most frequently performed for squamous cell carcinoma (SCC) and salivary duct histology. All other histologies were significantly less likely to undergo END compared to SCC (p < .05). Salivary ductal carcinoma and adenocarcinoma had the greatest rates of occult node disease (39.8% and 30.0%, respectively), followed by SCC (29.8%). Kaplan-Meier survival analysis showed a statistically significant increase in 5-year overall survival in patients who received END with poorly differentiated mucoepidermoid (56.2% vs 48.5%, p = .004) along with moderately and poorly differentiated SCC (43.2% vs 34.9%, p = .002; 48.9% vs 36.2%, p < .001, respectively). Histological classification is a benchmark for determining which patients should receive an END. We demonstrated an increase in overall survival in patients who undergo END with poorly differentiated tumors of mucoepidermoid and SCC histology. As such, histology should be considered along with clinical T-stage and rate of occult nodal metastasis to determine eligibility for END.

A Clinicopathological Evaluation of the Correlation of Carcinoma Oral Tongue (Anterior Two Thirds) with Cervical Nodal Metastasis to Assess the Level of Neck Dissection: A Hospital Based Prospective Study.

Being an important prognostic predictor in carcinoma oral tongue, neck metastasis poses an adverse impact on prognosis.The management of neck is still controversial. Neck metastasis depends on features like tumor thickness, depth of invasion, lymphovascular invasion and perineural invasion. Thus by correlating these features with the level of nodal metastasis and by correlating clinical and pathological staging, a preoperative assumption for a more conservative neck dissection may be done. To correlate clinical staging, pathological staging and depth of invasion (DOI) of tumor with cervical nodal metastasis, for a preoperative assumption of a more conservative neck dissection.To study the correlation of additional prognostic features like lymphovascular invasion, perineural invasion, positive resection margin, worst pattern of invasion, lymphocytic infiltration and presence of necrosis with that of cervical nodal metastasis. The study was conducted on 24 patients of carcinoma oral tongue who underwent resection of the primary with an appropriate neck dissection and their clinical, imaging, and postoperative histopathological findings were correlated. We found a significant association of the CC (craniocaudal) dimension and radiologically determined DOI (depth of invasion) with the pN also significant association of clinical and radiological DOI with histological DOI. The probability of occult metastasis was found to be more when the MRI-DOI is > 5mm. The sensitivity and specificity of cN staging were 66.67% and 73.33% respectively. The accuracy of cN was 70.8%. In the present study a good sensitivity, specificity and accuracy of cN (clinical nodal stage) was found. Craniocaudal (CC) dimension and DOI of the primary tumor measured by MRI is a strong predictor of the disease extension and nodal metastasis. MRI-DOI > 5mm warrants an elective neck dissection of level I-III. For tumors MRI DOI < 5mm observation can be recommended with adherence to a strict follow-up.

Endoscopic Ultrasound Predicts Risk of Occult Intra-Abdominal Metastases in Localized Gastric Cancer: A Validation Study.

In gastric cancer (GC) patients without imaging evidence of distant metastasis, diagnostic staging laparoscopy (DSL) is recommended to detect radiographically occult peritoneal metastasis (M1). DSL carries a risk for morbidity and its cost-effectiveness is unclear. Use of endoscopic ultrasound (EUS) to improve patient selection for DSL has been proposed but not validated. We aimed to validate an EUS-based risk classification system predicting risk for M1 disease. We retrospectively identified all GC patients without positron emission tomography (PET)/computed tomography (CT) evidence of distant metastasis who underwent staging EUS followed by DSL between 2010 and 2020. T1-2, N0 disease was EUS "low-risk"; T3-4 and/or N+ disease was "high-risk". A total of 68 patients met inclusion criteria. DSL identified radiographically occult M1 disease in 17 patients (25%). Most patients had EUS T3 tumors (n = 59, 87%) and 48 (71%) patients were node-positive (N+). Five (7%) patients were classified EUS "low-risk" and 63 (93%) were classified "high-risk". Of 63 "high-risk" patients, 17 (27%) had M1 disease. The ability of "low-risk" EUS to predict M0 disease at laparoscopy was 100% and DSL would have been avoided in five patients (7%). This stratification algorithm showed a sensitivity of 100% (95% confidence interval (CI): 80.5-100%) and a specificity of 9.8% (95% CI: 3.3-21.4%). Use of an EUS-based risk classification system in GC patients without imaging evidence of metastasis helps identify a subset of patients at low-risk for laparoscopic M1 disease who may avoid DSL and proceed directly to neoadjuvant chemotherapy or resection with curative intent. Larger, prospective studies are needed to validate these findings.

Central Compartment Neck Dissection in Laryngeal and Hypopharyngeal Squamous Cell Carcinoma: Clinical Considerations.

Metastatic lymph node involvement represents the most relevant prognostic factor in head and neck squamous cell carcinomas (HNSCCs), invariably affecting overall survival, disease-specific survival, and relapse-free survival. Among HNSCCs, laryngeal and hypopharyngeal cancers are known to be at highest risk to metastasize to the central neck compartment (CNC). However, prevalence and prognostic implications related to the CNC involvement are not well defined yet, and controversies still exist regarding the occult metastasis rate. Guidelines for the management of CNC in laryngeal and hypopharyngeal cancers are vague, resulting in highly variable selection criteria for the central neck dissection among different surgeons and institutions. With this review, the authors intend to reappraise the existing data related to the involvement of CNC in laryngeal and hypopharyngeal malignancies, in the attempt to define the principles of management while highlighting the debated aspects that are lacking in evidence and consensus. Furthermore, as definition and boundaries of the CNC have changed over the years, an up-to-date anatomical-surgical description of the CNC is provided.

Rate of occult neck nodal metastasis in primary and salvage laryngectomy.

Rate of occult neck nodal metastasis in primary and salvage laryngectomy.

Letter to the Editor Re: Yamamoto R, Sugiura T, Ashida R, Ohgi K, Yamada M, Otsuka S, and Uesaka K. Prognostic value of carbohydrate antigen 19-9 and the surgical margin in extrahepatic cholangiocarcinoma. Ann Gastroenterol Surg. 2022; 6:307-315.

We have read with great interest a manuscript that demonstrated margin status having a significant impact on OS in the group of patients with the lowest preoperative Ca19-9 value.1 In contrast, in two other groups with increased preoperative Ca19-9, the OS rate of the R0 and R1 resection did not differ. Here we would like to comment on the hidden message of this interesting paper referring to the data which is shown exceptionally in tables and figures but is not remarked on in the article. In the presence of minimal margins, R1 dramatically worsened the survival chances in the best prognosis group and did not have an impact on medium (B) or high-risk (C) groups. Paradoxically, R1-exhibiting patients in the low-risk A group were exhibiting not only inferior OS as compared to R0 patients of their own normal group (fig. 3A) but also as compared to R1 patients in normalization (fig. 3B) or non-normalization (fig. 3C) groups. It seems that the authors initially aimed for an ambitious and difficult objective: to explore tumor marker Ca19-9 reduction achieved during the surgical intervention to evaluate the completeness of resection and to predict the prognosis of EHCC. An analysis of Table 1 reveals interesting findings. The degree of Ca19-9 reduction as a result of tumor debulking surgery was more pronounced in two higher-risk groups (also designated as “B” and “C” in some tables) as compared to the low-risk (A) group. The postoperative decline of the Ca19-9 value in the normal group can be calculated as 1.6 times reduction (from 16 to 10 U/mL); whereas it exhibited a significantly better reduction—4.1 times in the highest risk group (C). Finally, the highest reduction of Ca19-9 was seen in the B group—it exhibited 8 times decline. Nevertheless, patients in the B and C groups exhibited inferior overall survival regardless of margin status. Obviously occult distant metastasis at a time of surgical intervention in groups B and C resulted in inferior survival outcomes. The distant recurrence parameters later in time are remarkably worse in groups B and C (table 2). We would like to offer the rate of change of Ca19-9 in the early postoperative period to evaluate the completeness of surgical intervention. A specific growth rate (SGR) with negative values at the early postoperative period requires only two time points. Interestingly SGR can be compared between patients with no exact time points of blood sampling. The rate of tumor marker decline during an early postoperative period can signal the presence of positive margins or occult metastasis.2, 4 Similarly, SGR calculation following surgical resection for patients in remission3, 4 can be helpful in finding patients at risk of recurrence early. The monitoring of completeness of resection in oncology has been a point of debate over the past several decades.5 The absolute value of Ca19-9 should be less specific and less sensitive in identifying recurrence as compared to SGR, at least in theory. We are grateful for the authors providing us with many takeaways and ideas. The authors claim no conflict of interest. All the comments of this letter are in accordance with the Helsinki Declaration of 1964 and later versions.

Elective Neck Dissection Improves Regional Control in cN0 Minor Salivary Gland Carcinoma in the Oral Cavity

Consensus regarding whether elective neck dissection (END) provides better outcomes than observation in clinically node negative minor salivary gland (MSG) carcinoma is lacking. Therefore, this study aimed to compare the impact of END with that of observation on regional control (RC) and overall survival (OS) and to detect the predictors for lymph-node metastasis in oral MSG carcinoma. A single-institution, retrospective cohort study was designed; it included patients with clinically node negative oral MSG carcinoma treated at a tertiary teaching hospital between January 2002 and January 2022. The primary predictor variable was END and primary outcome variables were RC and OS. The secondary outcome variable was lymph-node metastasis. Other covariates included demographic and pathologic features, TNM stage, and adjuvant treatment. The Kaplan-Meier method and Cox proportional hazards model were used to determine the effect of END on RC and OS. The chi-squared test and logistic regression models were used to identify independent predictors for lymph-node metastasis. A total of 268 patients (107 men and 161 women) with a mean age of 46.4±15.5years were included. The 5-year RC rate was statistically different between the observation and END groups (75%; 95% confidence interval [CI], 67%-83; 95% CI, 81%-93%, respectively; P=.014). Cox regression analysis confirmed that END (hazard ratio [HR] 2.395; 95% CI: 1.433-8.275; P=.034) was independently associated with a decreased risk of regional recurrence. The 5-year OS rates for the observation and END groups were 66% (95% CI, 56-76%) and 76% (95% CI, 66-86%), respectively, and the difference was not statistical (P=.057). Occult metastasis occurred in 24.6% of patients. Primary tumor location on the tongue/floor of the mouth (odds ratio [OR], 4.287; 95% CI, 1.773-9.125; P=.011), T3/4 stage (OR, 3.286; 95% CI, 1.228-8.253; P=.021), and high-grade disease (OR, 6.674; 95% CI, 2.199-14.326; P<.001) were independently associated with an increased risk of occult metastasis. RC was better with END than with observation, but OS was comparable with the two approaches. Primary tumor location on tongue/floor of the mouth, T3/4 stage, and high-grade disease were associated with an increased risk of lymph-node metastasis.

Early postoperative decrease of skeletal muscle mass predicts recurrence and poor survival after surgical resection for perihilar cholangiocarcinoma

BackgroundPreoperative sarcopenia is a predictor of poor survival in cancer patients. We hypothesized that sarcopenia could progress as occult metastasis arose, especially after highly invasive surgery for highly aggressive malignancy. This study aimed to evaluate the associations of postoperative changes in skeletal muscle mass volume with survival outcomes in patients who underwent surgery for perihilar cholangiocarcinoma.MethodsFifty-six patients who underwent major hepatectomy with extrahepatic bile duct resection for perihilar cholangiocarcinoma were studied. The skeletal muscle index (SMI) at the third lumbar vertebra was calculated from axial computed tomography images taken preoperatively and 3–6 months postoperatively (early postoperative period). The associations of clinicopathological variables, including changes of SMI after surgery, with overall survival and recurrence-free survival were evaluated. Moreover, the associations of decreased SMI and elevated serum carbohydrate antigen 19–9 level with early recurrence and poor survival was compared.ResultsAmong 56 patients, 26 (46%) had sarcopenia preoperatively and SMI decreased in 29 (52%) in the early postoperative period. During the median follow-up of 57.9 months, 35 patients (63%) developed recurrence and 29 (50%) died. Decreased SMI in the early postoperative period was independently associated with a shorter overall survival (hazard ratio, 2.39; 95% confidence interval, 1.00–6.18; P = 0.049) and a shorter recurrence-free survival (hazard ratio, 2.14; 95% confidence interval, 1.04–4.57; P = 0.039), whereas elevated carbohydrate antigen 19–9 level was not.ConclusionsDecreased SMI in the early postoperative period may be used as a predictor for recurrence and poor survival in patients undergoing surgery for perihilar cholangiocarcinoma.