Regional Nodal Spread Research Articles

Appendiceal adenocarcinoma-patterns of tumor spread and prognosis

IntroductionAppendiceal adenocarcinoma represents a diagnostic and therapeutic challenge since it is prone to early lymphatic and peritoneal spread. We aimed to analyze the proportion of lymph node metastases in completion right hemicolectomy specimens, risk factors for peritoneal metastases (PM), and prognosis after definitive treatment. MethodsNinety-three patients with appendiceal adenocarcinoma scheduled for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) in Uppsala 2004–2020 were identified from a prospectively maintained registry. Risk factors for PM were assessed based on the presence (CT + group, n = 55) or absence (CT – group, n = 37) of visible PM at baseline CT scan. Prognostic factors were analyzed based on the actual presence (PM group, n = 66) or absence (no PM group, n = 27) of PM. ResultsThe median age was 60 (26–78). Forty-eight patients were women. Resection of PM at initial surgery indicated an 80 % risk of finding PM at a follow-up exploration. R1 appendectomy and perforated appendix had a similar risk for PM (24 %,26 %) which increased to 38 % if both were present.Regional lymph node metastases occurred in 31 % in the CT + group vs. 14 % in the CT − group (p = 0.005) and was associated with poor survival HR 5.16 (1.49–17.81).The 5-year OS and DFS rates were 54 % and 29 % in the PM group. ConclusionsPatients with certain risk factors have a high likelihood of PM despite a normal CT scan, which justifies selective exploration at a HIPEC center. Regional lymph node spread supports the current practice of completion right hemicolectomy and is a significant prognostic factor.

MED15::ATF1-Rearranged Tumor: A Novel Cutaneous Tumor With Melanocytic Differentiation

We recently described novel dermal tumors with melanocytic differentiation and morphologic and biological similarities to cutaneous clear cell sarcoma, including CRTC1::TRIM11 cutaneous tumor, and clear cell tumors with melanocytic differentiation and either ACTIN::MITF or MITF::CREM. Here, we describe a series of 3 patients presenting with tumors reminiscent of CRTC1::TRIM11 cutaneous tumor, found to demonstrate a novel MED15::ATF1 fusion. All 3 patients were children (5-16 years old). Primary excision of case 1 showed a circumscribed wedge-shaped silhouette with peripheral intercalation into collagen fibers and scattered lymphoid aggregates. All 3 tumors abutted the epidermis; one showed a junctional component. Tumors were highly cellular and comprised of monomorphic, oval-to-round epithelioid cells arranged in vague nests and short fascicles in variably fibrotic stroma. Mitotic rate was high (hotspot 6-12/mm2), without atypical mitoses. Necrosis was focally present in case 3. All cases showed strong, diffuse nuclear staining for SOX10 and MITF (2/2) but showed variable expression for S100 protein (1/3) and other melanocytic markers—Melan-A (focal in 2/3), HMB45 (focal in 1/3), and Pan-Melanoma (patchy in 1/1). Whole-exome RNA sequencing demonstrated a MED15::ATF1 fusion without any other notable alterations. Cases 1 and 2 were completely excised without recurrence (12 months). Case 3 developed a grossly apparent regional lymph node spread shortly after primary biopsy. The patient was treated with wide excision, radiation, cervical lymph node dissection (4/46 with >75% lymph node replacement), and neoadjuvant and adjuvant nivolumab (alive without disease at cycle 11). This series is presented to aid in future diagnosis of this novel dermal tumor with melanocytic differentiation and emphasize the potential for aggressive biologic behavior, which should be considered in patient management planning.

Role of 68Ga-PSMA PET/CT in Initial Staging of Prostate Cancer and Correlation with PSA and Gleason Score

Background Prostate cancer is the second most common male malignancy. Its prognosis depends on the tumor stage as well as its aggressiveness; expressed histopathologically by Gleason scores. Furthermore, optimal patient management depends on the tumor stage. 68Ga PSMA PET/CT has a wide spectrum of uses in prostate malignancy, some of them are comprehensively studied while others are still under investigation. The most widely accepted use is the accurate initial staging of cancer prostate as well as predicting the long-term outcome, with SUVmax being a promising prognostic parameter correlating significantly with other established prognostic parameters, including the Gleason score and the PSA levels. Objective To evaluate the role of 68GA- PSMA PET/CT in initial staging of prostate cancer and correlate with PSA level and Gleason score. Methods A prospective descriptive study over the course of 6 months. It included patients with pathologically proven prostate cancer referred for a PSMA PET/CT scan for initial staging without any treatment or interventions. Results 68Ga-PSMA PET/CT scans of 36 patients were evaluated for local staging (primary prostatic lesions, extra-prostatic spread, and seminal vesicle invasion), regional nodal staging, and metastatic spread (extra-regional lymph nodes, osseous lesions, and visceral lesions). PET/CT findings as well as the SUVmax of the most avid lesions were correlated with PSA level, Gleason scores, as well as Gleason grade risk groups. A statistically significant relationship was found between PSA level and SUVmax of prostatic lesion as well as that of the most avid metastatic regional lymph node, the presence of extra-regional lymph nodal spread, the presence of osseous metastatic lesions, the presence of seminal vesicle invasion, extra-prostatic extension, and the presence of PSMA-avid regional lymph nodal spread. On the other hand, a statistically significant relationship was found between Gleason scores and the presence of regional lymph nodal spread and osseous metastatic lesions. Lastly, a statistically significant relationship was found between Gleason grading risk groups and the presence of regional lymph nodal spread and osseous metastatic lesions. Conclusion 68Ga-PSMA PET/CT is a powerful staging and stratifying tool for the majority of prostate cancer patients, being significantly correlated with PSA level and Gleason scores. However, patients with low PSA scores still pose a dilemma as they showed significantly low PSMA uptake, rendering the use of 68Ga-PSMA PET/CT for staging in such patients controversial. 68Ga-PSMA PET/CT based imaging findings should ideally be supported with histopathological documentation and/or follow-up imaging results in order to confirm the nature of detected lesions and help establish accurate sensitivity and specificity of 68Ga-PSMA PET/CT.

Reliability of MRI in Pre-Therapeutic Assessment of Tumor Depth Invasion in Oral Cavity Carcinoma

Background Head and neck carcinomas account for 5% of all cancers, with approximately half of those arising from the oral cavity, thus creating a significant health problem. Accurate loco-regional staging determines the appropriate treatment plan and subsequently favorable outcome and disease prognosis. Patients & Methods 20 patients (12 females and 8 male) were included in this study. Conventional MRI, diffusion MRI and Dynamic contrast MRI were performed for local and nodal disease staging. MRI staging was correlated to operative histopathology as a reference standard. Diagnostic accuracy was estimated for MRI techniques. Results Results revealed high accuracy of MRI in local tumor and nodal staging. Conclusion MRI remains the cornerstone in loco-regional staging of tongue carcinoma. DCE-MRI is the most accurate MRI technique in evaluation of local extension and depth of invasion. Combination of DCE-MRI and DWI-MRI achieves highest accuracy for detection of regional nodal spread.

Factors associated with failure to operate and its impact on survival in early-stage pancreatic cancer.

Curative intent for localized pancreatic cancer (pancreatic ductal adenocarcinoma [PDAC]) requires surgery, but despite improved perioperative outcomes, surgery remains underutilized. This study analyzed the Texas Cancer Registry (TCR) to identify resectable PDAC patients who underwent curative-intent surgery in Texas between 2004 and 2018. We then evaluated demographic and clinical factors associated with failure to operate and survival (OS). We identified patients with localized PDAC or regional lymph node spread between 2004 and 2018 in the TCR. Resection rates were determined and multivariable regression and cox proportional hazards were used to identify factors associated with failure to OS. Of 4274 patients, 22% underwent resection, 57% were not offered surgery, 6% had comorbidities precluding surgery, and 3% refused. Resection rates decreased from 31% in 2004 to 22% in 2018. Increasing age was associated with failure to operate (odds ratio [OR] 2.55; 95% confidence interval [CI] 1.80-3.61; p < 0.0001) while treatment at a Commission on Cancer (CoC) center correlated with reduced failure to operate (OR 0.63; 95% CI 0.50-0.78; p < 0.0001). Resection correlated with survival (HR 0.34; 95% CI 0.31-0.38; p < 0.0001) as did treatment at a National Cancer Institute (NCI)-designated center (hazard ratio 0.79; 95% CI 0.70-0.89; p < 0.0001). Surgery is underutilized for the treatment of resectable PDAC in Texas with decreasing utilization, annually. Evaluation at CoC was associated with improved resection rates and NCI was associated with increased survival. Expanding access to multidisciplinary care including trained hepato-pancreatico-biliary surgeons may improve outcomes for PDAC patients.

S3438 Malignant Gastrointestinal Neuroectodermal Tumor of the Small Intestine: A Rare Cause of Iron Deficiency Anemia

Introduction: Gastrointestinal neuroectodermal tumors (GNET) are a type of high-grade sarcoma of the gastrointestinal (GI) tract that share features with clear cell carcinoma of tendon sheaths and aponeuroses. Patients typically present with clinical signs and symptoms of small bowel obstruction, intussusception or abdominal mass. These tumors can arise in the stomach, colon, as well as metastasis to liver or regional lymph nodes. We present a case of ileal GNET in an otherwise asymptomatic patient with Iron-deficiency Anemia (IDA) diagnosed using video capsule endoscopy (VCE). Case Description/Methods: A 58-year-old Hispanic male with a past medical history of GERD and obesity presented for evaluation of chronic microcytic anemia. Workup revealed: hemoglobin 8.6 g/dl, MCV 62.2, iron saturation 2.6%, transferrin 307 mg/dl, ferritin < 5 ng/ml, reticulocyte index of 1.34; serum folate, vitamin B12 and TSH levels were within normal limits. He was taking oral ferrous sulfate and vitamin C for IDA. He reported heartburn but denied melena, hematochezia, hematemesis, weight loss and had an unremarkable colonoscopy four years prior. Upper endoscopy revealed mild erosive esophagitis and mild chronic active gastritis with negative biopsies. Colonoscopy was unremarkable in the setting of optimal bowel preparation. VCE revealed an ulcerated mass occupying 35% of the ileal lumen. CT of the abdomen noted asymmetric wall thickening with enhancement of the small bowel. The patient underwent laparoscopy-assisted enteroscopy with rendezvous technique allowing direct visualization of a 3 cm proximal ileum mass requiring open segmental resection with primary anastomosis. Pathology suggested malignant GNET or clear cell sarcoma-like tumor of the GI tract. Immunohistochemistry was positive for neural crest markers (S100, SOX10) and Vimentin; negative for CD117, DOG1, HMB45, MART1, MAA, chromogranin, and synaptophysin. Fluorescence in-situ hybridization was positive for EWSR1 (22q12) rearrangement. Given the clear surgical margins, absent regional lymph node spread and lack of standard guidelines for this rare pT1N0M0 tumor, surveillance imaging every three months without adjuvant radiation or systemic chemotherapy was recommended. (Figure) Discussion: This case highlights the importance of VCE for small bowel assessment after negative bidirectional endoscopy to identify the etiology of IDA per American Gastroenterology Association guidelines. In this case, an ulcerated GNET was the etiology of IDA persisting despite iron supplementation.Figure 1.: A-Luminal view of small bowel tumor on Video Capsule Endoscopy (VCE) B–Close up view of ulceration of small bowel tumor on VCE C–Histopathology slide showing epithelioid cells with eosinophilic cytoplasm, pleomorphic nuclei with prominent nucleoli and vesicular nucleoli. Scattered mitotic figures identified.

Adoption of Adjuvant Chemotherapy in High-Risk Salivary Gland Malignancies

<h3>Purpose/Objective(s)</h3> Surgical resection and radiation therapy remain the primary modalities of treatment for patients with salivary gland malignancies. The role of adding adjuvant concurrent chemoradiotherapy (CRT) versus radiotherapy (RT) alone in this group is currently under investigation in a clinical trial (RTOG 1008). We investigated the patterns of care and adoption of adjuvant chemoradiotherapy in treatment of high-risk salivary malignancies. <h3>Materials/Methods</h3> All adult patients in the National Cancer Database (NCDB) with salivary gland malignancies diagnosed from 2004 to 2018 were identified. Patients with unspecified squamous cell carcinoma or with distant metastases were excluded. High-risk pathological features in this study were defined as positive surgical margins, lymphovascular invasion, regional lymph node spread, grade 2-4, and stage T3-4. The proportion of patients receiving adjuvant CRT was calculated per year. Linear regression analysis was performed on the CRT:RT proportion across the study period. Kaplan-Meier survival analysis was performed on a sample of propensity score-matched patients based on age, sex, tumor histology, staging, margins, and comorbidities. <h3>Results</h3> During the study period, 33,262 adult patients with salivary gland malignancies were identified. Among those patients, 17,361 (52.2%) patients received adjuvant RT, of which 3,333 (19.2%) received concurrent chemotherapy. Among the patients who received RT, 13,891 (80.0%) had high-risk features, of which 3076 (22.1%) received concurrent chemotherapy. The proportion of patients receiving chemotherapy across all pathologies increased from 18% to 28% (p<0.001) over the study period. Use of chemotherapy in high-risk patients increased from 21% to 35% (p<0.001). Among different histologies, significant increases were seen in acinic cell carcinoma (2% to 14%, p<0.001), adenoid cystic carcinoma (8% to 15%, p<0.001), and adenocarcinoma (27% to 51%, p<0.001); but no increases in mucoepidermoid carcinoma (16% to 17%, p=0.47) and carcinoma ex pleomorphic adenoma (20% to 34%, p=0.27) were observed. In a 213 propensity score-matched population, no significant difference in overall survival (p=0.4) was observed between patients who received chemotherapy and those who did not. <h3>Conclusion</h3> While no clinical trial data is available, a significant increase in the use of adjuvant CRT is seen in patients with salivary gland malignancies with or without high-risk features, and in certain histologies. We could not identify any associated survival benefit in this patient population. The upcoming trial (RTOG 1008) could determine if there is a benefit in adding chemotherapy to adjuvant radiotherapy.

Diagnostic performance of a novel high-resolution dedicated axillary PET system in the assessment of regional nodal spread of disease in early breast cancer.

In early breast cancer, a non-invasive method with higher sensitivity and negative predictive value (NPV) is needed to identify and recognize more indolent axillary lymph nodes (ALNs). This study aimed to assess whether a novel high-resolution dedicated ALN positron emission tomography (LymphPET) system could improve sensitivity in detecting early breast cancer (clinical N0-N1 stage). A total of 103 patients with clinical stage T1-2N0-1M0 breast cancer were evaluated by 18F-fluorodeoxyglucose (18F-FDG) LymphPET. The maximum single-voxel PET uptake value of ALNs (maxLUV) and the tumor-to-background ratio (TBR) for fat (TBR1) and muscle (TBR2) tissue were calculated. Then, 78 patients with cN0 stage breast cancer received sentinel lymph node biopsy alone or combined with axillary lymph node dissection (ALND), and 25 patients with cN1 stage breast cancer underwent fine-needle aspiration. A total of 99 invasive breast carcinoma cases were included in this study. The diagnostic sensitivity of LymphPET was 88%, specificity was 79%, false-negative rate was 12%, the false-positive rate was 21%, positive predictive value was 75%, NPV was 90%, and accuracy was 83%. The maxLUV was superior to TBR1 and TBR2 in detecting ALNs, with 0.27 being the most optimal cutoff value. The 18F-FDG LymphPET system can be used to identify and recognize more indolent ALNs of breast cancer due to greater sensitivity and a much higher NPV.

PET metabolic tumor volume as a new prognostic factor in childhood rhabdomyosarcoma.

Childhood RMS is a rare malignant disease in which evaluation of tumour spread at diagnosis is essential for therapeutic management. F-18 FDG-PET imaging is currently used for initial RMS disease staging. This multicentre retrospective study in six French university hospitals was designed to analyse the prognostic accuracy of MTV at diagnosis for patients with RMS between 1 January 2007 and 31 October 2017, for overall (OS) and progression-free survival (PFS). MTV was defined as the sum of the primitive tumour and the largest metastasis, where relevant, with a 40% threshold of the primary tumour SUVmax. Additional aims were to define the prognostic value of SUVmax, SUVpeak, and bone lysis at diagnosis. Participants were 101 patients with a median age of 7.4 years (IQR [4.0-12.5], 62 boys), with localized disease (35 cases), regional nodal spread (43 cases), or distant metastases (23). 44 patients had alveolar subtypes. In a univariate analysis, a MTV greater than 200 cm3 was associated with OS (HR = 3.47 [1.79;6.74], p<0.001) and PFS (HR = 3.03 [1.51;6.07], p = 0.002). SUVmax, SUVpeak, and bone lysis also influenced OS (respectively p = 0.005, p = 0.004 and p = 0.007) and PFS (p = 0.029, p = 0.019 and p = 0.015). In a multivariate analysis, a MTV greater than 200 cm3 was associated with OS (HR = 2.642 [1.272;5.486], p = 0.009) and PFS (HR = 2.707 [1.322;5.547], p = 0.006) after adjustment for confounding factors, including SUVmax, SUVpeak, and bone lysis. A metabolic tumor volume greater than 200 cm3, SUVmax, SUVpeak, and bone lysis in the pre-treatment assessment were unfavourable for outcome.

Locoregional Extension Patterns of Nasopharyngeal Carcinoma Detected by FDG PET/MR.

PurposeWe sought to define the locoregional extension patterns of nasopharyngeal carcinomas (NPCs) by positron emission tomography (PET)/magnetic resonance imaging (MRI) and to improve clinical target volume (CTV) delineation.MethodsBetween May 2017 and March 2021, 331 consecutive patients with nonmetastatic NPCs who underwent pretreatment, simultaneous whole-body PET/MRI for staging were included in this study.ResultsThe high-risk regions included the base of the sphenoid bone, the prestyloid compartment, prevertebral muscle, foramen lacerum, medial pterygoid plate, sphenoidal sinus, clivus, petrous apex, and foramen ovale. When the high-risk regions were invaded, the incidence rates of tumor invasion into the medium-risk regions increased. In contrast, when the high-risk regions were not involved, the incidence rates of tumor invasion into the medium-risk regions were mostly less than 10%, excluding the post-styloid compartment and oropharynx. According to the updated consensus guidelines of the neck node levels for head and neck tumors from 2013, level IIa (77.3%, 256/331), level IIb (75.8%, 251/331), and level VIIa (71.3%, 236/331) were the most frequently involved levels, followed by levels III (42.6%), Va (13.9%), IVa (8.8%), IVb (3.6%), Ib (3.6%), Vb (2.4%), VIIb (2.4%), VIII (1.8%), Vc (0.9%), and Xa (0.3%). Skip lymph node metastasis occurred in only 1.9% of patients.ConclusionsFor NPCs, primary disease and regional lymph node spread follow an orderly pattern, and a skip pattern of lymph node metastasis was unusual. Involved level radiotherapy might be feasible for cervical lymph node levels below the caudal border of cricoid cartilage and level VIIb.

Frequency and Risk Factors for Metastasis in Newly Diagnosed Appendiceal Carcinoma.

BackgroundAppendiceal carcinoma has an insidious clinical presentation, and these tumors are rarely suspected prior to surgery, potentially leading to late diagnosis. The aim of this study is to investigate the prevalence of metastatic disease at initial presentation and potentially associated sociodemographic characteristics.MethodsPatients were identified from the Surveillance, Epidemiology, and End Results (SEER) program using the International Classification of Diseases for Oncology-3 (ICD-O-3) histology/behavior codes between 2010 and 2015. Firth logistic regression was performed to determine the association of metastasis at presentation with tumor subtype, adjusted for age, race, sex, insurance and marital status, tumor grade, and tumor and nodal stage using the 7th edition of the American Joint Committee on Cancer (AJCC) staging system.ResultsWe identified a total of 3,447 patients with known metastatic status. A total of 38.4% had metastatic disease at diagnosis. Compared to colonic-type adenocarcinoma (CA), mucinous adenocarcinoma (MA) and signet ring cell carcinoma (SC) were more likely to present with metastasis at diagnosis (OR: 2.34; 95% CI [1.80- 3.06]; OR: 1.93 [1.29-2.89], respectively), however, goblet cell carcinoma (GC) was less likely (OR: 0.59 [0.36-0.93]). Compared to tumors invading the submucosa (T1 stage), tumors invading deeper through the visceral peritoneum or nearby organs (T4 stage) were significantly more likely to present with metastatic disease (OR: 3.46 [2.24-5.51]). Tumors invading the muscularis propria (T2 stage) or deeper into the subserosa, or the mesoappendix (T3 stage) were less likely to present with metastatic disease (OR: 0.34 [0.16-0.71]); OR: 0.55 [0.34-0.91], respectively). Compared to no regional lymph node spread, four or more regional lymph node involvement (N2 stage) was more likely to present with metastatic disease (OR: 2.19 [1.53-3.16]). Men were less likely to present with metastatic disease (OR: 0.60 [0.48-0.73]). A total of 90.1% of CA, 84.2% of GC, 42.2% of MA, and 78.5% of SC patients with metastasis at diagnosis had extraperitoneal distant metastasis (M1b).ConclusionsA significant proportion of patients with newly diagnosed appendiceal carcinoma presented with metastatic disease, concerning substantial diagnostic delay and potentiating the need for aggressive treatments. Predictors of metastatic disease included female sex, histologic subtype, and significant regional lymph node involvement. Future research should focus on earlier detection and explore tumor biology.

The Pattern of Cervical Lymph Node Metastasis and Risk Factors of Retropharyngeal Lymph Node Metastasis Based on Magnetic Resonance Imaging in Different Sites of Hypopharyngeal Carcinoma.

BackgroundThis study was to determine the patterns of regional lymph node (LN) spread and the risk factors of retropharyngeal lymph node (RPLN) metastasis based on magnetic resonance imaging (MRI) in hypopharyngeal squamous carcinoma (HPC) to improve clinical target volume (CTV) delineation.MethodsA cohort of 326 consecutive patients of HPC in a single institute were retrospectively reviewed. All patients underwent MRI prior to initial treatment, and the diagnosis based on MRI of the LN metastasis was confirmed by all radiation oncologists in the head and neck group during twice weekly chat rounds. Statistical analysis of data was using chi-square test and multivariant logistic regression model in SPSS 22.0 software.ResultsThe LN metastasis rate of all patients in this cohort was 90.5% (295/326). Level IIa/b and level III were the most frequently involved regions followed by level IV and retropharyngeal region. Skip metastasis only occurred in 6.4% (19/295). Univariate and multivariate analysis demonstrated that primary tumor subsites were located in the posterior pharyngeal wall (P=0.002), bilateral cervical LN metastasis (P=0.020), larger volume of primary gross target (GTVp, P=0.003), and larger volume of LN gross target (GTVnd, P=0.023) were significantly associated with RPLN metastasis.ConclusionThe regional LN spread of HPC follows an ordered pattern as level II is the most frequently involved area followed by level III, level IV, and RPLN. RPLN metastasis is more likely to occur in patients with primary site of posterior pharyngeal wall, large tumor burden, or bilateral neck LN metastasis. Therefore, it is highly recommended that the RPLN should be included into CTV for patients who have these risk factors.

Prognostic Utility of Apical Lymph Node Metastasis in Patients With Left-sided Colorectal Cancer.

Unlike the tumor nodes metastasis (TNM) lymph node classification, based solely on counts of nodal metastases, the Japanese system of classifying colorectal carcinoma (CRC) focuses on regional lymph node spread. In this study, we explored the prognostic utility of inferior mesenteric artery (IMA) apical lymph node (APN) metastasis. This was a retrospective study of patients with stage III left-sided CRC. All enrollees were subjected to D3 resection between April 2007 and December 2016 at the International Medical Center of Saitama Medical University and then stratified by histologic presence (APN+ group) or absence (APN- group) of tumor in APNs examined postoperatively. Ultimately, propensity score matching was invoked (1:2) and COX regression analysis was conducted, determining group rates of relapse-free survival (RFS) and cancer-specific survival (CSS). A total of 498 patients were studied, grouped as APN+ (19/498, 3.8%) or APN- (479/498, 96.2%). Prior to matching, the APN+ (vs. APN-) group showed significantly more lymphatic involvement (73.7% vs. 47.8%; p=0.023), deep (T3/T4) tumor infiltration (100% vs. 78.9%; p=0.024), and nodal metastasis (N2: 84.2% vs. 27.6%; p<0.001). In addition, para-aortic nodal recurrences were significantly increased (15.7% vs. 2.0%; p<0.001), conferring worse RFS (p<0.001) and CSS (p=0.014) rates. Once baseline factors were matched, the two groups appeared similar in RFS (p=0.415) and CSS (p=0.649). Multivariate regression analysis indicated that elevated carcinoembryonic antigen (CEA) level and deep tumor infiltration were independent risk factors for RFS, whereas postoperative complications and tumor-positive node counts were independent risk factors for CSS. APN+ status was not a significant risk factor for RFS or CSS. APN positivity may thus constitute a regional rather than systemic manifestation. The TNM staging based on the number of metastatic lymph nodes seems to be more reasonable than the regional lymph node classification method.

Delayed post-diuretic 18F-FDG PET/CT: can it help in determination of the best clinical decision for muscle invasive UB cancer patients?

Background18F-Fluorodeoxyglucose positron emission tomography-computed tomography (18F FDG PET/CT) has been used previously in the staging of the bladder cancer patients. Its main role was to detect regional nodal metastatic spread as well as distant organ metastasis but it was limited in detection of the primary neoplasia and the local tumor recurrence in the urinary bladder due to the presence of excreted radiotracer in the urinary tract, masking the urinary bladder lesion and probably the adjacent small regional metastatic lymph nodes. The aim of this study was to highlight the efficacy of delayed post-diuretic 18F-FDG PET/CT in staging and restaging muscle invasive urinary bladder cancer (MIBC), allowing metabolic evaluation of the primary disease, in addition to detection of associated metastasis which in turn can help to determine the best clinical decision for patients. This prospective study included 35 patients with MIBC, divided into two main groups: group A (18 patients) coming for initial staging and group B (17 patients) coming for post-therapeutic assessment. All patients of both groups were analyzed by a multidisciplinary team and the clinical decisions before and after PET CT were analyzed.ResultsIn group A, 7/18 patients were upstaged with consequent changing in therapeutic management. No downstaging was reported.In group B, the response was reported in 11/17 patients where they proceeded to radical surgery with an excellent agreement to pathological findings. 3/17 patients were stationary and 3/17 patients were progressed.PET/CT helped in the determination of the best treatment decision in 68.6% of patients among both groups.ConclusionDelayed post-diuretic PET/CT imaging is an important diagnostic tool in evaluation MIBC patients, which may consequently help to determinate the best clinical decision for them.

Management Issues in Conjunctival Tumours: Conjunctival Melanoma and Primary Acquired Melanosis.

Conjunctival melanoma is a rare malignant condition of the ocular surface. It is potentially lethal, with regional lymph node spread often preceding distant solid-organ metastasis. Due to its rarity and the long latency between treatment and local recurrence or the development of metastases, it is difficult to study. The literature is composed entirely of case series of varying quality, and there is significant variability in the management of this condition. This commentary attempts to distil the evidence base to provide practical management tips for the clinician.

Nodal drainage pathways in primary rectal cancer: anatomy of regional and distant nodal spread.

Nodal involvement is a significant prognostic factor in rectal cancer and difficult to assess preoperatively. An understanding of the patterns of nodal spread from different regions of the rectum can assist in this process and is essential for the purposes of surgical planning. In this article we define patterns of spread to mesenteric and pelvic sidewall nodal subgroups and discuss the importance of accurate anatomic localization of nodes for the purposes of staging and surgical planning.

The effect of RORa expression on the development of biological malignancy of urinary bladder cancer

Background: Morbidity and mortality relating to urinary bladder cancer have remained largely unchanged for many years. Similarly, the five-year survival rate in this disease has not improved considerably. New developments in individualized therapy necessitate the search for novel factors that could predict the development of malignancy in UBC. In this study, we provide the first evidence that the expression of ROR alpha transcription factor influences the development of malignancy in UBC. Materials and methods: 105 patients with stage pT1-pT4 urothelial bladder carcinoma who underwent cystectomy were included in the study. 4 μm tissue samples were stained immunohistochemically with a polyclonal anti-RORa antibody. The expression of RORa by the tumor cells (TCs) was assessed by counting TCs with a cytoplasmic and/or nuclear staining for RORa per 1000 TCs. The association between the extent of RORa expression and non-classic differentiation, tumor advancement (pT), grade (G) and regional lymph node spread was analyzed. Results: The cytoplasmic expression of RORa was detected in near all analyzed tumor samples (104/105). The extent of RORa expression was significantly higher in tumors which were more malignant with more propensity for non-classic differentiation and lymph node metastasis. We noted a lower percentage of TCs expressing RORa in poorly differentiated tumors (G3), compared to tumors moderately and higher differentiated (G1/G2). Conclusions: Our results suggest that RORa may play a significant role in the progression of urinary bladder cancer. RORa has a broad spectrum of regulatory activity relating to cell and tissue differentiation the mechanism of which is not fully understood. This study represents another step in the process of understanding the mechanisms of RORa regulation and highlights its potential role as a therapeutic target in urothelial bladder cancer.

The Patterns of Cervical Lymph Node Metastasis and Risk Factors of Retropharyngeal Lymph Node Metastasis Based on MR Imaging in Different Sites of Hypopharyngeal Carcinoma

This study aimed to determine the patterns of regional lymph node (LN) spread and the risk factors of retropharyngeal lymph node (RPLN) metastasis based on magnetic resonance imaging (MRI) in hypopharyngeal squamous carcinoma (HPC), to improve clinical target volume (CTV) delineation. A cohort of 326 consecutive patients of HPC were retrospectively reviewed. All patients got available MR imaging before they received definitive radiation therapy or surgery. The rate of LN metastasis was 90.5% (295/326). Level IIa/b and level III were the most frequently involved regions followed by level IV and retropharyngeal region. Skip metastasis occurred in only 6.4% (19/295). Univariate and multivariate analyses demonstrated that primary tumor subsites (p=0.002), bilateral cervical lymph node metastasis(p=0.020), GTVp (p=0.003) and GTVnd (p=0.023) were significantly associated with RPLN metastasis. Regional LN spread follow an orderly pattern as Level II was the most frequently involved followed by level III and RPLN in hypopharyngeal carcinoma. RPLN metastasis was more likely occur in patients with primary site of posterior pharyngeal wall, large tumor burden, and bilateral neck LN metastasis.

Ability of Dual-Energy CT to Detect Silicone Gel Breast Implant Rupture and Nodal Silicone Spread.

The purpose of this study is to compare the performance of dual-energy CT (DECT) with that of breast MRI for detection of silicone gel breast implant rupture and nodal spread of silicone. This prospective study enrolled consecutive patients with current or prior silicone gel implants and clinical suspicion of implant rupture or extra-capsular silicone. All patients underwent MRI followed by unenhanced DECT. A breast radiologist not participating in image evaluation established reference standards for implant rupture (intra- or extracapsular) and regional nodal silicone spread (to axillary nodes and internal mammary [IM] and mediastinal nodes) using MRI, surgical findings, and medical records. After undergoing reader training, two radiologists who were blinded to all medical records interpreted randomized images in two sessions, indicating confidence in diagnosis using a 100-point visual scale. A total of 46 patients who had a subpectoral silicone gel implant (n = 31), a subglandular silicone gel implant (n = 14), or a silicone gel implant that was removed (n = 1) underwent MRI and DECT (mean [± SD] volume CT dose index, 8.2 ± 2.0 mGy). Nineteen patients had implant rupture, and 13 of these patients had silicone within the IM or axillary nodes. Pooled data showed no significant difference between MRI and DECT interpretation of intra- or extracapsular rupture of implants (AUC value for intracapsular rupture, 0.958 [for MRI] vs 0.989 [for DECT]; p = 0.28; AUC value for extracapsular rupture, 0.864 [for MRI] vs 0.878 [for DECT]; p = 0.78). No difference was noted in the AUC value for silicone spread to regional lymph nodes: 0.823-0.866 [for MRI] vs 0.892-0.906 [for DECT]; p = 0.34-0.54). DECT performs similar to MRI for the detection of silicone gel implant rupture and the presence of silicone in regional lymph nodes, and it may be an alternative for patients who are unable or unwilling to undergo MRI.

Cutaneous Non-Neural Granular Cell Tumors Harbor Recurrent ALK Gene Fusions.

Non-neural granular cell tumor (NNGCT; also known as primitive polypoid granular cell tumor) is a rare neoplasm composed of large ovoid cells with abundant granular cytoplasm, variable nuclear pleomorphism, and the potential for regional lymph node spread. In contrast to conventional granular cell tumor (GCT), NNGCT lacks S100 expression and can exhibit greater nuclear atypia and mitotic activity. Therefore, we investigated clinicopathologic features of 12 NNGCT, and also used next-generation sequencing to identify potential driver events in a subset of NNGCT and 6 GCT. NNGCT demonstrated mild-to-moderate nuclear pleomorphism, variable mitotic activity (0 to 10/10 high-power fields), and were S100. Genetic analysis of 5 cutaneous NNGCT revealed gene fusions involving the anaplastic lymphoma kinase gene (ALK) in 3 cases (60%). Specifically, an interstitial deletion of chromosome 2 resulting in an in-frame fusion of dyanactin 1 (DCTN1) to ALK was identified in 2 cases, and a translocation resulting in a fusion between sequestosome 1 (SQSTM1) on chromosome 5 and ALK was identified in one case. Two of 6 GCT (33%) showed gains of chromosome 7. No other molecular or chromosomal alterations were detected in NNGCT and GCT. ALK immunohistochemistry revealed weak-to-moderate positivity in 4/9 cutaneous NNCGT (44%) including all 3 tumors with ALK fusions. Three oral NNGCT lacked ALK expression. NNGCT with ALK immunostaining did not have morphologic features distinguishing them from those without ALK staining. Our results demonstrate that a subset of NNGCT harbor ALK fusions, suggest that NNGCT are molecularly diverse, and further substantiate NNGCT as distinct from GCT.